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UVM / Nutrition and Food Sciences / NFS 243 / Why do enzyme systems important?

Why do enzyme systems important?

Why do enzyme systems important?

Description

School: University of Vermont
Department: Nutrition and Food Sciences
Course: Advanced Nutrition
Professor: Stephen pintauro
Term: Spring 2015
Tags: nutrition
Cost: 25
Name: NFS243 Advanced Nutrition
Description: Whole bundle of a lot of stuff! All my class notes, some exam study guides.. PDF's we wrote about.
Uploaded: 02/15/2016
114 Pages 32 Views 2 Unlocks
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NFS 243 Advanced Nutrition Exam #1 11/4/15 7:24 PM 1/21 


Why do enzyme systems important?



Induction: inducing the synthesis of the enzyme. Does not tell you about the  activity 

Examples of inducing agents related to nutrition: cruciferous vegetables  (associated with a reduced risk of cancer) this is related to enzyme induction  ∙ Broccoli  phase 1 and phase 2 drug metabolizing enzymes (DMEs) ∙ Enzyme systems are important in handling toxins from the outside and  the inside 

∙ Benzopyrene [found in cigs] belongs to a group of chemicals called PAH  (polycyclic aromatic hydrocarbons)

o Heated at high temps it’s a potent cancer causing substance 

o BUT, they do NOT cause cancer if found in their form in the 

environment: very stable and doesn’t break down in the 

environment 


What group does benzopyrene belong to?



o This is dangerous because when you inhale it, your body converts  it into a product that is not stable and cancer forming  We also discuss several other topics like What are the three central coordinates problems?

(ENVIORNMENT = OK : BODY = BAD) 

 Belongs to the group of phase 1 metabolizing enzymes (the 

enzymes that break down the stable form and make it 

unstable)

o After phase 1 metabolism, additional enzymes act on the substrate  known as phase 2 metabolism and phase 2 metabolism results in 

conjugation to form a water soluble product 

 This cancer causing form undergoes further metabolism 

where is it conjugated (a side group is added to the 

compound, usually polar) something that makes the 

compound MORE polar by adding the side group. 


What is the use of pcbs?



We also discuss several other topics like What is resonance?

 After its conjugated to a more water soluble compound, this 

compound can be more easily excreted. The goal of phase 2 

is to get rid of the toxin by excreting it in the urine. 

     Problem: you need to go through phase 1 to get to phase 2.  

 phase 1 makes the compound more dangerous 

∙ broccoli is a good inducer for phase 1 and phase 2

∙ PCBs = used for many years in manufacturing. (found in the lake)

o Bc of the old use of this material from paper mills

o PCBs are extraordinarily stable. Once in environment they last  forever. Inducers for phase 1 metabolism. Can accelerate other  chemicals to cause cancer. They aren’t cancer, they increase the  risk of other things to have a higher risk of cancer. 

1/23 

stock and flow diagram = 

∙ like a bucket. If you add inflow (intake) the stock (weight) equals the  expenditure (subtractions or outflows) 

∙ for food: if you turn up the intake, your body weight will go up, if you  return your food intake equal to your expenditure, it wont drain, it will  just stay at that elevated level 

Biological Energy (video clip)

∙ Oxidative phosphorylation 

o your body uses a lot of energy and has to make a lot of energy  o energy needed for ATP production is derived from the energy  generated by the flow along a series of substrate oxidation and  reduction  Don't forget about the age old question of What is it called when an item is for both genders?

o starts with substrates in the Krebs Cycle

o “dehydrogenase” enzymes catalyze removal of hydrogen’s and  electrons from Krebs Cycle substrates

∙ two mechanisms for ATP production in the cell

o substrate­level phosphorylation 

o oxidative phosphorylation  

 begins in the Krebs cycle 

 energy that is used to drive oxidative, is initially provided by these dehydrogenase enzymes in the ETC

what drives the flow of e­ along the ETC?

∙ depends on “standard reduction potential” of reduction­oxidation (redox)  pairs

∙ “standard reduction potential” is a measure of a substances tendency to  lose e­ 

∙ the more negative the “SRP” the greater the tendency to lose e­ ∙ the less negative (more positive) the “SRP” the greater the tendency to  gain e

short video showed in class:

∙ the ETC (electron transport chain)

o series of protein complexes in the mitochondria 

o  basic electron transport chain information (will be posted on  blackboard)

2/6 

celiacs disease – an allergic response that causes inflammation. Its an  autoimmune disease. 

2/11 We also discuss several other topics like How does the sensation of stimulus get transmitted to the brain?
Don't forget about the age old question of What do positive statements mean?

 Celiac Disease and Gluten Sensitivity 

Autoimmune disease – immune reaction to the individual 

Gluten = general term for various prolamin proteins found in wheat, barley,  rye, oats

∙ Prolamins = plan storage proteins 

∙ Relatively high in proline and glutamine

∙ Only soluble in strong alcohol solution

CD = 1 in 133 Americans (1 in 4,700 are ever diagnosed)

∙ Diagnosis

o Specific autoantibodies (anti­glidin, anti­endomysium, anti  trans…)

o Specific genetic (HLA­DQ genes)

o Enteropathy 

o The small intestine lining is damaged 

How do you diagnose gluten sensitivity? 

∙ 1. Test for celiac disease = negative Don't forget about the age old question of What does a reversible reaction mean?

∙ 2. Try a gluten free diet

∙ 3. Rechallenge 

DISCUSSED THE PDF FOR GLUTEN DIET THING THAT IS POSTED ON  THE NOTE PAGE

** Now back to the protein PowerPoint **

1/14 Podcast Notes 

more amine groups = more potentially for a rxn

hydrolyzed proteins + sugar (or reducing compound) = malliard rxn  food industry LOVES malliard rxn for making aromas and flavors  

NBC news story – played in class

∙ Is a chemical compound found in caramel coloring a health risk? ∙ ^^ chemical causes cancer in animals

∙ artificial caramel coloring in sodas

o 4-MEi

∙ 4-MEi  

o coloring food brown, we don’t need to increase cancer risk to  color a food brown

∙ too much soda = extra calories and extra sugars you don’t need  ∙ soda drinking is declining over the years, YAY

4-Methylimidazole  

∙ how is it made?

∙ Synthesis reaction of methylgloxcal and ammonia and formaldehyde

o Methylgloxcal = compound that ends with AL is an aldehyde   Two aldehydes reacting with ammonia to form this  pigment  

o What about glucose allows them to react?

 What kind of sugar is glucose?

 Its an ALDOSE sugar  

 Glucose has 6 carbons  

 The #1 carbon in sugar is an aldehyde (HC=O)  Aldehydes (CH=O) and ketose sugar [fructose]  (RCR=O)

 Carbonyls include aldehydes and ketones  

 WHENEVER we talk about these rxns, we talk about  them how they relate to other carbonyls that might be  present in us

 They can be found and come up in lipid oxidation  (fatty acids break down) some of the products  

include that. And when they react with amines it  can cause this rxn.  

 HbAlc = related to diabetes  

 Carbonyl compounds like to react with amines and they  do not need enzymes. They can just interact on their  own.

^^ this is a basic structure for a carbonyl  this is an aldehyde 

this is a ketone 

NFS 243 Advanced Nutrition Exam #1 2/20/15 10:41 AM 1/21 

Induction: inducing the synthesis of the enzyme. Does not tell you about the  activity 

Examples of inducing agents related to nutrition: cruciferous vegetables  (associated with a reduced risk of cancer) this is related to enzyme induction  ∙ Broccoli  phase 1 and phase 2 drug metabolizing enzymes (DMEs) ∙ Enzyme systems are important in handling toxins from the outside and  the inside 

∙ Benzopyrene [found in cigs] belongs to a group of chemicals called PAH  (polycyclic aromatic hydrocarbons)

o Heated at high temps it’s a potent cancer causing substance 

o BUT, they do NOT cause cancer if found in their form in the 

environment: very stable and doesn’t break down in the 

environment 

o This is dangerous because when you inhale it, your body converts  it into a product that is not stable and cancer forming 

(ENVIORNMENT = OK : BODY = BAD) 

 Belongs to the group of phase 1 metabolizing enzymes (the 

enzymes that break down the stable form and make it 

unstable)

o After phase 1 metabolism, additional enzymes act on the substrate  known as phase 2 metabolism and phase 2 metabolism results in 

conjugation to form a water soluble product 

 This cancer causing form undergoes further metabolism 

where is it conjugated (a side group is added to the 

compound, usually polar) something that makes the 

compound MORE polar by adding the side group. 

 After its conjugated to a more water soluble compound, this 

compound can be more easily excreted. The goal of phase 2 

is to get rid of the toxin by excreting it in the urine. 

     Problem: you need to go through phase 1 to get to phase 2.  

 phase 1 makes the compound more dangerous 

∙ broccoli is a good inducer for phase 1 and phase 2

∙ PCBs = used for many years in manufacturing. (found in the lake)

o Bc of the old use of this material from paper mills

o PCBs are extraordinarily stable. Once in environment they last  forever. Inducers for phase 1 metabolism. Can accelerate other  chemicals to cause cancer. They aren’t cancer, they increase the  risk of other things to have a higher risk of cancer. 

1/23 

stock and flow diagram = 

∙ like a bucket. If you add inflow (intake) the stock (weight) equals the  expenditure (subtractions or outflows) 

∙ for food: if you turn up the intake, your body weight will go up, if you  return your food intake equal to your expenditure, it wont drain, it will  just stay at that elevated level 

Biological Energy (video clip)

∙ Oxidative phosphorylation 

o your body uses a lot of energy and has to make a lot of energy  o energy needed for ATP production is derived from the energy  generated by the flow along a series of substrate oxidation and  reduction 

o starts with substrates in the Krebs Cycle

o “dehydrogenase” enzymes catalyze removal of hydrogen’s and  electrons from Krebs Cycle substrates

∙ two mechanisms for ATP production in the cell

o substrate­level phosphorylation 

o oxidative phosphorylation  

 begins in the Krebs cycle 

 energy that is used to drive oxidative, is initially provided by these dehydrogenase enzymes in the ETC

what drives the flow of e­ along the ETC?

∙ depends on “standard reduction potential” of reduction­oxidation (redox)  pairs

∙ “standard reduction potential” is a measure of a substances tendency to  lose e­ 

∙ the more negative the “SRP” the greater the tendency to lose e­ ∙ the less negative (more positive) the “SRP” the greater the tendency to  gain e

short video showed in class:

∙ the ETC (electron transport chain)

o series of protein complexes in the mitochondria 

o  basic electron transport chain information (will be posted on  blackboard)

2/6 

celiacs disease – an allergic response that causes inflammation. Its an  autoimmune disease. 

2/11 

 Celiac Disease and Gluten Sensitivity 

Autoimmune disease – immune reaction to the individual 

Gluten = general term for various prolamin proteins found in wheat, barley,  rye, oats

∙ Prolamins = plan storage proteins 

∙ Relatively high in proline and glutamine

∙ Only soluble in strong alcohol solution

CD = 1 in 133 Americans (1 in 4,700 are ever diagnosed)

∙ Diagnosis

o Specific autoantibodies (anti­glidin, anti­endomysium, anti  trans…)

o Specific genetic (HLA­DQ genes)

o Enteropathy 

o The small intestine lining is damaged 

How do you diagnose gluten sensitivity? 

∙ 1. Test for celiac disease = negative

∙ 2. Try a gluten free diet

∙ 3. Rechallenge 

DISCUSSED THE PDF FOR GLUTEN DIET THING THAT IS POSTED ON  THE NOTE PAGE

** Now back to the protein PowerPoint **

1/14 Podcast Notes 

more amine groups = more potentially for a rxn

hydrolyzed proteins + sugar (or reducing compound) = malliard rxn  food industry LOVES malliard rxn for making aromas and flavors  

NBC news story – played in class

∙ Is a chemical compound found in caramel coloring a health risk? ∙ ^^ chemical causes cancer in animals

∙ artificial caramel coloring in sodas

o 4-MEi

∙ 4-MEi  

o coloring food brown, we don’t need to increase cancer risk to  color a food brown

∙ too much soda = extra calories and extra sugars you don’t need  ∙ soda drinking is declining over the years, YAY

4-Methylimidazole  

∙ how is it made?

∙ Synthesis reaction of methylgloxcal and ammonia and formaldehyde

o Methylgloxcal = compound that ends with AL is an aldehyde   Two aldehydes reacting with ammonia to form this  pigment  

o What about glucose allows them to react?

 What kind of sugar is glucose?

 Its an ALDOSE sugar  

 Glucose has 6 carbons  

 The #1 carbon in sugar is an aldehyde (HC=O)  Aldehydes (CH=O) and ketose sugar [fructose]  (RCR=O)

 Carbonyls include aldehydes and ketones  

 WHENEVER we talk about these rxns, we talk about  them how they relate to other carbonyls that might be  present in us

 They can be found and come up in lipid oxidation  (fatty acids break down) some of the products  

include that. And when they react with amines it  can cause this rxn.  

 HbAlc = related to diabetes  

 Carbonyl compounds like to react with amines and they  do not need enzymes. They can just interact on their  own.

^^ this is a basic structure for a carbonyl  this is an aldehyde 

this is a ketone 

Emily Dickinson

Madison Whitaker

Lauren Leaverson

Sierra Dessureault 

PDF of Gluten

Fructans – a fructan is a poorly absorbed carbohydrate that can induce symptoms by themselves.  An example of a fructan is an inulin. The side effects of inulin dietary fiber in sensitive persons  include, intestinal discomfort, bloating, cramping

IBS – is a disorder that leads to abdominal pain and cramping, changes in bowel movements and  other symptoms. In IBS, the structure of the bowel is NOT abnormal. 

Crohn’s disease is strongly associated with specific HLA class II genes, known as HLA­DQ2  and HLA­DQ8.  Celiac disease was excluded by the ABSENSE of HLA­DQ2 and HLA­DQ8  haplotype.

Serum­IgA is used to test for IgA deficiencies, a harmless condition associated with celiac  disease that can cause a false negative tTg­IgA or EMA result. 

Gliadin antibodies are produced in response to gliadin, a prolamin found in wheat. In bread  wheat, there are three different alleles, AA, BB and DD. Each allele can produce slightly  different versions of gladins, which can cause the body to produce different antibodies. IgA is  found in about 80% of patients with coeliac disease. Majority of these patients have neuropathies that respond favorably to a gluten elimination diet. IgG is similar to IgA but is found at higher  levels in patients with IgA­less phenotype. It is associated with idiopathic gluten sensitivity. 

C­reactive protein is a substance that is produced by the liver that increases the presence of  inflammation in the body. This would be measured to see if someone has inflammation after  consuming something that had gluten, because if they had Celiac disease, the inflammation  would grow, and if they didn’t it wouldn’t. 

Lactoferrin would be measured because it can rule our irritable bowel syndrome in patients  presenting with inflammatory bowel disease symptoms. 

Statistical power is a test that detects the effect and to see if it actually exists. It is an association  between causal relationships of two variables. The paragraph is talking about the relationship of  the placebo effect and the estimated response to gluten when there was no previous data.

The kappa statistic takes into account the agreement occurring by chance. It is a statistical  measure of inter­rater agreement occurring by chance. It is a statistical measure of inter­rater  agreement for qualitative terms. 0.24 falls into the “fair agreement” category. The lower the k 

number, the less agreement there was so that it means that there was little or “fair” connection to  participants knowing what group they were in. 

A priori power analysis is conducted prior to the research study, and is typically used in  estimating sufficient sample sizes to achieve adequate power. So the authors are saying that even though they knew prior to the study that their sample size was too small to determine a true  effect from the study, that they did have a big result from it, so that it was big enough to draw  conclusions from. 

Tiredness was a symptom that differed the most between the groups. It follows up by saying that  tiredness is associated with gluten, and it could provide insights into its mechanism of action.  This relates to the overall value of this experiment that gluten actually does cause a significant  quantitative difference in people who claim to be sensitive to it. The researchers predict that  gluten promotes a systemic response of tiredness in the body. 

Even though they don’t act on the disease, placebos seem to affect how people feel. This happens in up to 1 out of 3 people. A change in a person’s symptoms as a result of getting a placebo is  called the placebo effect. This effect usually lasts only a short time. It’s thought to have  something to do with the body’s natural chemical ability to briefly relieve pain or certain other  symptoms. But sometimes the effect goes the other way, and the placebo seems to cause  unpleasant symptoms or worse. These may include headaches, nervousness, nausea, or  constipation, to name a few of the possible “side effects.” The unpleasant effects that happen  after getting a placebo are sometimes called the nocebo effect. Together, these 2 types of  outcomes are sometimes called expectation effects. This means that the person taking the placebo may experience something along the lines of what he or she expects to happen.

Lyndi Wieand   Help from: Allie Raevsky and Lauren Jacques

Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease PDF Question  Responses 

1. What are “fructans?” Fructans are a type of soluble fiber carbohydrate that may cause  irritation in the intestines of people, with symptoms such as gas, diarrhea, distention and  other uncomfortable symptoms. They are found naturally in foods and also are added to  many others to an added fiber content without changing their taste or texture. They are part  of a group of carbs called FODMAPs, which stands for fermentable oligo­di monosaccharides and polyols.

2. What is Irritable Bowel Syndrome (IBS)? Irritable Bowel Syndrome is a common disorder  which affects the colon, causing diarrhea, cramping, abdominal pain, bloating, gas, and  constipation. It can be controlled by managing one’s diet, lifestyle and stress levels, or  sometimes with medication if needed. 

3. What are HLA­DQ2 and HLA­DQ8 and what is their relationship to Celiac Disease?  HLA molecules are postulated to present gluten antigens to T­cells which then cause tissue  damage to the intestine. Approximately 95% of people with Celiac Disease have HLA­DQ2,  which is encoded by two different alleles, and about 5% of people have HLA­DQ8, which is  encoded by another two different alleles. It is rare for people to carry only one of the DQ2  alleles. In the U.S., 25­40% of the population has one of the two DQ haplotypes, but it is not always a cause of Celiac Disease. There may be HLA­DQ typing done in order to rule out  Celiac Disease and genetic susceptibility for it. 

4. What are the relationships of these biomarkers to Celiac Disease? Tissue  transglutaminase IgA and/or a whole gliadin (IgA or IgG) test is a way doctors evaluate  patients for celiac disease. The immune system response in celiac disease involves the  production of antibodies directed against an enzyme present in the intestines called tissue  transglutaminase, or tTG. The antibodies IgA and IgG are produced by the body and attack  tTG. Measuring the IgA form of tissue transglutaminase antibody in the blood is a more  efficient and useful way of diagnosing CD because it is made in the small intestine, which is  where gluten affects the lining and causes inflammation and irritation to those who are  sensitive to gluten. It may not be as important, but it is a useful way to measure the levels of the IgG form of tTG antibody to diagnose the condition in people who are unable to make  regular amounts of IgA. 

5. Why did they measure highly sensitive C­reactive protein? High levels of C­reactive  protein in blood plasma can be an indication of chronic inflammation in the body, particularly in the small intestine. 

6. Why was fecal lactoferrin measured? This test is mainly indicated to detect the presence  of colitis in the setting of acute or chronic diarrhea, or to assess for the presence of or the  activity of chronic forms of colitis such as ulcerative colitis or Crohn's colitis in persons with  suspicious intestinal symptoms. 

7. What is statistical “Power” and what is this paragraph describing? Statistical “power”   is the probability that a statistical test correctly rejects the null hypothesis, when proven  false. This paragraph is describing how, by using the placebo effect, there was an estimated 60% response of subjects to having gluten sensitivity, but there was no previously recorded  data to do any comparison to. This also showed that there needed to be 30 patients in each group in order to have a power value of 80% and a P value of 0.05. 

Lyndi Wieand   Help from: Allie Raevsky and Lauren Jacques

1. 80% is describing the ability of the experiment to avoid type II errors: conclude that there is no significant difference in your groups; 80% chance for detecting that the difference  is actually thee

2. 0.5 describes the 95% probability that you have not encountered a type I error: rejecting  the null hypothesis when you shouldn’t. P value is less than 5%. 

8. How does this "kappa statistic" indicate that the blinding was successful?  A kappa  statistic is an indication of the difference between how much agreement is actually present  compared to how much agreement would be expected to be present by chance alone. A  score of 0.24 is relatively low, showing that participants had a low agreement between the  actual treatment they received and how much they guessed they received. 

9. What are the authors saying here, in relation to the "Power" of their experiment? The  “Power” of the experiment ended up being smaller than they began with, but the analyses  confirmed that the smaller number of participants was enough to get a statistically  satisfactory result, having a distinct separation between the placebo and gluten groups. 1. if they didn’t find a significant result, you would have had to determine if you had enough subjects for power

10. What do you think it relates to the overall value of this experimental design and the  results? A common symptom of IBS may be tiredness, however, tiredness is a common  symptom daily in people is tiredness over the course of the day. I believe this relates to the  overall value of this design and results such that gluten may have been giving participants a different effect from which they would have had from IBS. 

11. Although the Gluten Group reported significantly higher results for these symptom  severities, the placebo group still showed increases in severity for many of these  symptom as well.  What do you think accounts for this? The symptom severities  between the placebo group and the gluten group could have been due to a possible change in one’s diet from consuming the bread and muffins. The placebo group participants most  likely had their bowels under control and running normally, but with the addition of these  foods to their diet, it may have triggered their bodies to induce symptoms, even if the breads and muffins contained gluten or not. 

NFS 243 Advanced Nutrition Exam #2 02/20/2015 2/20 Protein  

Functional categories of proteins

∙ Enzymes

∙ Hormones

∙ Structural proteins  

Eicosanoid biosynthesis  

∙ Omega-3 fatty acid

∙ When a tissue is injured eracondonic acid is released  

∙ Phosphoplipase-A-2 because it’s cleaving from the 2nd carbon on the glycerol backbone  

∙ If you eat a lot of fish, your cell membrane will have large amounts  of EPA and not ETA  

∙ So lots of fish = EPA and EPA is different because it has 5 double  bonds. When EPA enters the pathway, it’s different than ETA. It’s a  different compound because it has another double bond. That extra  double bond really effects the activity of these compounds.

∙ The anti-inflammatory properties of EPA = less potent leukotriene’s  compared to when ETA enters the pathway  

NFS 243 Advanced Nutrition Exam #2 3/25/15 11:26 AM 2/20 Protein  

Functional categories of proteins

∙ Enzymes

∙ Hormones

∙ Structural proteins  

∙ Immunoproteins  

∙ Transport proteins

∙ Other  

o They all perform many different functions – related to their  

structure  

Amino acids, joined by peptide bonds : alpha amino group (on carbon)  and alpha carboxylic acid (on carbon)  

∙ Which of these amino acids would you expect to readily reaction  with glucose?  

o Answer: Lysine – amines like to react with aldehydes (glucose  is an aldose sugar – reducing sugar, can easily react with  

amines)  

 Has amine group sticking out, wants to react with  

aldehyde  

Glycated hemoglobbin

∙ More likely to react with proteins in the blood – reacts with amines  (glucose does)

∙ BINDS TO LYSINE

Hemoglobin A1C is used for monitoring glucose control in diabetes –  measures how your glucose over a long period of time once glucose is bound it doesn’t come off – its irreversible  

∙ Better than measuring blood glucose levels (change a lot)  ∙ Everyone has some hemoglobin A1C – so there is a normal level,  like 4% , for ppl with diabetes it can go higher to 9% à indicates that over the life of that blood cell, the glucose levels have be high  ∙ When glucose levels are elevated in the blood – interact with lots of  protein, not just hemoglobin, glucose also glycates other proteins  ∙ Glucose is a reducing sugar, can react with amines, one of them is  hemoglobin, but there are others! (whatever amines are present)  [NON ENZYMATIC RXNS]  

 ALDEHYDES (glucose) likes to react with AMINES

Essential amino acids

∙ Threonine

∙ Lysine

∙ Histidine  

o All of these are totally indispensable  

∙ Trytophan  

∙ Methionine  

∙ Isoleucine  

∙ Leucine  

∙ Valine  

∙ Phenylalanine  

Body cant produce these in sufficient amounts  

∙ 3 of them are totally indispensable – no pathways in the body found  to make these (histidine, lysine, threonine)

∙ Histidine: only need a tiny amount, no pathway for synth of it, but  would be very difficult to be deficient of this bc you only need a very little amount

∙ Whole egg = benchmark quality protein  

∙ Trypotphan – none in gelatin (a kind of protein)  

∙ Methionine and cystein are grouped together: one is a precursor to  the other (meth. Spares the amt of cystein you need)

∙ Phenalalanine and tyrosine are grouped together: one is a precursor to the other (phenala. Spares the amount of tyrosine you need)  

Anabolic or catabolic pathways (for the amino acid)

∙ Anabolism – synth of proteins  

∙ Catabolism: moving off an amine group (transamination reaction) to an other compound or deaminate it (just remove the amine group)  ∙ alpha-keto-acids: amino group has been removed from alpha  carbon, meaning ketone group is on alpha carbon amine group  usually goes into synth of other amino acids

∙ carbon skeleton (after you remove amine group) – can be broken  down for energy, used for glucose, converted to ketone bodies used for energy, converted to Fas

Transaminatin Rxns

∙ Transfer of amine groups from one acid to another  ∙ Transaminase enzymes do this !  

∙ ALT – transfers aa from alanine  

∙ AST- transfers aa from aspartate  

∙ Which vitamin is required for these transaminase reactions? -  Vitamin B6 (is a coenzyme)  

∙ Pyridoxal phosphate – has an aldehyde (at the top) – is vitamin B6  (is the aldehyde version of vitamin B6) – aldehydes like to pair with  amines – amine group from Aspartate – doesn’t bind  irreversibly – is reversible  

∙ 1. pyridoxal binds to amine group on enzyme

∙ 2. amine from Aspartate is substituted for amine group on  pyridoxal à pyridox amine

∙ 3. pyridox amine donates amine to alpha keto skeleton to form  new amino acid  

∙ B6 in pyridoxal – required for these transaminase reactions –  aldehydes reacting with amines – this case is a very specific way  

Diagnostic Value of plasma aminotransferase

∙ AST and ALT used for diagnostic purposes  

∙ elevated levels in blood: indication of issues

o if both are elevated in blood – indication of liver disease –  normally would be low in the blood (but high in liver) – when  there is liver damage – levels go up in blood, (liver cells  die – necrosis)--> leak their content into the blood  

∙ Heart Muscle: normally high in AST and low in ALT, if blood is high in AST then indicates a heart attack – death of heart tissue  

Important N-containing non-protein compounds

∙ Leukotrienes: class of compounds known as EICOSANOIDS –  derived from fatty acids – leukotrienes: involved in inflammation  and immune response\

∙ Glutathione plays a role in leukotriene biosynthesis  ∙ Has antioxidant properties  

Eicosanoid biosynthesis  

∙ Leads into omega 3 Fas and fish oils

∙ Eicosanoids : all are derived from arachidonic acid – a Fatty acid  – polyunsaturated FA, 20C long, 4 double bonds - is a precursor of  synth of eicosanoid compounds  

∙ arachidonic acid is in cell membranes (in lipid bilayer – is bound in  the bilayer) – if injured – its mobilized from lipid bilayer- cleaved off  from phospholipid stores by phospholipase A2 enzyme : this  enzyme is activated by injury or inflammation. Then the acid can do further metabolism and form different kinds of eicosanoids  ∙ Forms prostoglandins  

∙ Inhibits production of thromboxain – (inhibits the stimulation of  platelet aggregation)  

∙ Asprin/advil/ibuprofen – inhibit prostoglandin pathway – inhibits one  of them PGI2 – controls levels of mucous in stomach – can cause  stomach bleeding due to inhibition of PGI2 in the stomach and less  mucous so the stomach acid hurts the stomach

∙ Leukotriene C4 – gluasfjdsanflk is added  

Eicosanoid biosynthesis  

∙ Omega-3 fatty acid

∙ When a tissue is injured eracondonic acid is released  ∙ Phosphoplipase-A-2 because it’s cleaving from the 2nd carbon on the glycerol backbone  

∙ If you eat a lot of fish, your cell membrane will have large amounts  of EPA and not ETA  

∙ So lots of fish = EPA and EPA is different because it has 5 double  bonds. When EPA enters the pathway, it’s different than ETA. It’s a  different compound because it has another double bond. That extra  double bond really effects the activity of these compounds.

∙ The anti-inflammatory properties of EPA = less potent leukotriene’s  compared to when ETA enters the pathway  

Glutathione : elimination of toxins from the body

∙ Toxin  phase 1 metabolism  oxidized toxin intermediate  phase 2  metabolism and glutathione s-transferase  toxin-GSH conjugate  urine  

Glutathione: protect cells from free radical and peroxide damage  ∙ Cells are constantly producing reactive oxygen species  ∙ Superoxide – byproduct of many metabolic rxn’s in the cell. And our  

body needs to protect itself from these radicals that are formed. We  convert superoxide to hydrogen peroxide. We do not want hydroxyl  radical’s in the body (most damaging type that can be formed in the body)  

∙ We DO NOT WANT hydrogen peroxide to undergo further break  down to have it become a hydroxyl radical

∙ We need help that breaks down hydrogen peroxide and break it  down to hydrogen and water  

∙ Glutathione peroxidase  breaks down hydrogen peroxide and  makes it into water  

∙ Cysteine is a sulfur containing acid  

∙ G-S-S-G (oxidized form) = glutathione in it’s oxidized form ∙ G-S-S-G  glutathione reductase + riboflavin (FAD)  (2) G-S-H  (reduced form)  

o G-S-H is what is needed for the glutathione peroxidase rxn  Phenylalanine and tyrosine metabolism  

2/25 

when is the diet lacking in the amino acid lysine..

∙ protein synthesis will be limited  

which of the following is essential for the proper function of glutathione peroxidase?

∙ Selenium  

Phenylalanine and tyrosine metabolism

∙ Vitamin C is a reducing agent in some of these steps  

∙ Adrenal medulla  

Tryptophan metabolism  

∙ Essential amino acid

∙ Can undergo metabolism in a number of different directions  ∙ Tryptophan to serotonin (produced in the gut) 

o Melatonin in the pineal gland in the brain

Tryptophan is  

∙ Both glucogenic and ketogenic  

Methionine and cysteine metabolism  

∙ Are elevated levels of homocysteine a heart problem?  

∙ Methionine – contains sulfur

∙ 3 important vitamins

o vitamin b12, folate and vitamin b6

∙ betaine – betaine is found in certain foods but your body can also  make it. It has a particular structure that is more descriptive than  it’s name. it’s trimethylglycine. Betaine can be converted to  dimethylglycine which can suggest that it’s giving up a methyl  group. So a methyl group is being used to convert.  

∙ Homocysteine can go in two different directions

o It can be converted back to methionine  

 It can pick up a methyl group from vitamin b12 and go  back to methionine  

o Or homocysteine can be further converted to cysteine (this  one requires vitamin b6)

2/27 

∙ above is a table listing the content of selected amino acids in a  food, along with the ideal reference protein amounts of these amino acids. Which of the amino acids is the limiting essential amino acid  in food?

o Glycine

o Threonine

o Tryptophan

o Valine  

 Methionine and cysteine metabolism

∙ Vitamin B6 and vitamin B12 and folate are involved in this process  

 the conversion of methionine to S-adenonsyl methionine requires ∙ vitamin b6

∙ ATP

o Because adenonsyl is added, and it comes from the A in ATP  and gives it up  

∙ vitamin b12

∙ NADPH  

S-adenosylmethionine is required for which of the following? ∙ The conversion of phenylalanine to tyrosine  

∙ The conversion of tryptophan to serrotin

∙ Glutathione reductase  

∙ The conversion of norepinephrine to epinephrine  o The source of the methyl group is S-Ad.  

 Taurine is a byproduct of methionine and cysteine metabolism   3/11 

 history of hyperhomocysteinemia hypothesis

∙ increase an individuals risk of CVD  

∙ auto-oxidation of homocysteine yields superoxide’s and H2O2  o can then produce hydroxyl radical (initiate lipid peroxidation in endothelial cells and lipoproteins)

∙ impairment of nitric oxcide production and function

o no need for proper vascular function  

o no prevents platelet aggregation  

o no impairs  

if you have this deficiency your risk of heart disease goes up from 1 to  1.43

∙ you don’t now if this is cause and effect. Other things could play a  role. But it’s interesting that they found this slight increase.  Folic acid supplements and risk of CVD

L-glucose  the last hydroxyl is to the LEFT (when the highest # is  isometric carbons is to the left its L, when it’s to the right it’s D)  

Which is not a reducing sugar?

∙ Sucrose  b/c  

∙ ALL monosaccharide’s are reducing sugars  

Which of the following sugars is least healthy?

∙ It’s an opinion (what)

HFCS is closest in composition to which of the following sugars?  ∙ Sucrose is the correct answer. It’s essentially identical to sucrose.  ∙ Your body recognizes these two as nearly the same thing  

Open chained structure of glucose is not it’s most stable group. It likes  to react with alcohol groups to form this hemiacetal ring.

For it to be reducing, has to be an OPEN chain form (remember this) ∙ You have to identify which carbon you are looking at in a  disaccharide form  

∙ When maltose is put into solution it gives you either the alpha or  the beta form. It’s a reducing sugar, but it’s weak.  

∙ Sucrose is tricky tho. b/c carbon #1 on the glucose part of it isn’t  available to open up because it’s tied in the linkage. And carbon #2  on fructose, is the carbon that is the ketone carbon.  

3/20  

CARBOHYDRATES  

(WATCH VIDEO AND CATCH UP)

∙ hormonal regulation of PFK-1

o insulin levels are high compared to glucagon

 when this happens, that favors the Dephosphorylation  of the bifunctional enzyme. And when it’s in its  

dephosphorylated form, the PFK-2 part of the enzyme is  active. Whenever one side of the enzyme is active, the  other side is active.  

 Dephosphorylated = PFK-2 activated

 Phosphorylated = PFK-1 activated  

 **REMEMBER** High insulin : glucagon favors  

dephosphorylation and activated of PFK-2 

 what is the effect of a high G:I ratio on activity of  

PFK-2? 

∙ It would deactivate it  

 What is the effect of high I:G ratio on FBP-2 

∙ It would deactivate ate

o When insulin is high, bisphosphate is  

in its deactivated form  

 What is the effect of low G:I ratio on activity of  

PFK-2? 

∙ It activates it  

∙ Hormonal regulation of CHO metabolism

o Glucagon HIGH compared to insulin

 Can be seen when you’re fasting and your body is trying to increase gluconeogenesis  

o Causes an increase in cyclic AMP  

 Cyclic AMP is a 2nd messenger, and it relates to protein  kinase enzyme because it activates them  

HFCS  

∙ Manufacturing  

o Isolate the starch from the corn and hydrolyze it to produce  dextrose (synonym for glucose)  

3/25/15 

HFCS contains dangerous levels of “reactive carbonyls”  HFCS consumption can lead to “fructose intolerance”  HFCS stimulates lipogenesis

HFCS increases uric acid production, leading to a  

∙ Decrease in nitric oxide availability

∙ (necessary for normal vascular function)  

HFCS does not stimulate insulin and leptin release

∙ Nor does it inhibit ghrelin  

**review of the PDF on HFCS**

1. The credentials and credibility of any guest that he has on the  show.

2. The appropriateness and logic of any demonstration he used to  explain the topic.

3. The scientific validity of his (or his guest’s) explanation and  conclusions about the topic.

4. Your overall evaluation of the presentation of the topic.

Pre-dinner snack (I WANT EVERYONE TO MAKE A PART OF THEIR ROUTINE) Eat 1-2 hours before dinner

Helps you lose 8 lbs a year

NO credible sources, just members from the audience  

Logic is NOT appropriate. He hand fed the lady.  

Had a weird image of digestion process that he put on the audience women  and didn’t explain well

Pre-dinner snack rules  

 6g of fiber because it “kick starts digestion”

10 g protein “hormones are important for burning off fat and keeping your  full. Protein satiates you”

“blasts away belly fat” called a power plate  

1 thin piece prosciutto, two olives (the mono-unsaturated fats will  eliminated belly fat) WHERE IS THIS TRUE?!, chick peas and zucchini

need to eat this snack 1-2 hours before dinner  

audience members liked the snacks, no credible sources still  mini pizza – 100% whole wheat pita, (how is this a snack? It’s a dinner thing)  is this a cooking show or a doctor recommendation?  

Skinny dips and chips – blue potato chips – compound that tricks your body  into thinking you’re supposed to be thin so your body starts to do what thin  peoples bodies do (WHAT DOES THIS EVEN MEAN?!) tricks your body into  wanting to be thin, it does what thin peoples bodies do

Cheese apple sandwich drops weight -  

Lemon slows down your ability to absorb sugar (according to?)

Pizza popcorn (bored snack) – 200 cals (snack all day long and you’re good to go)

Boost energy – cinnamon kicks up metabolism (according to?) Zappos – giving away lunch bags that has nothing to do with this.

Emily Dickinson

Madison Whitaker 

Annotated PDF on HFCS

1. The article states that the rise in obesity has a link with high fructose corn syrup.  However, I agree with the second statement that suggests that the added sugars  in general are causing this rise in obesity. This is due to the fact that more and  more people are eating less healthy foods for the quick grab and go affect and  aren’t eating properly balanced meals. People drink lots of sodas and eat a lot of  foods with added sugars that aren’t needed.

2. High fructose corn syrup is said to not produce satiety, or the feeling of being full, but meals with sucrose in them do. I agree with this because a person can eat a  meal with natural sugars, not added sugars, and feel full after a meal, where as  one who eats sugary foods with HFCS may not feel the same way as eating a  well balanced meal.

3. Ab libitum means “at ones pleasure”, or as much as one desires.

4. It does not make sense to me because if they are comparing HFCS with sucrose  as dissolved solutions, they should be the same percentage to yield better  results. With different percentages you would get different results. 

5. Interpreting results and measured weekly. HFCS, sucrose and chow intakes  were measured daily, and body weight was measured weekly. They recorded  this and kept track in the different experimental groups.

6. If they did not see effects of sucrose on body weight with males in experiment  one, they did not include sucrose groups in long­term analysis. However I think  they should of in order to correctly compare the group’s effect on the males.

7. Important when interpreting results were how they took measurements of HFCS  and chow, in experiment 1.

8. If I was in charge of the experiment, I would include both males and females in  each experiment and at the same age to keep the consistency. I would do the  same with a control group and record their body weights for all groups weekly. I’d include females to see if it effected them differently than how it effects males. 

9. The animals who consumed the 8% HFCS gained more weight than the 10%  sucrose group. This could be because they were only exposed to it for 12 hours  and when it was presented they consumed more of it. This could be because 

they were storing more of the sucrose than HFCS instead of using the sucrose  as energy.

10.In figures 2 and 4, it shows the increased abdominal weight gain in males and  females over a 24 or 12 hour period with HFCS. The males showed an increased abdominal fat pad weight gain as well as the females. The females showed an  increase in abdominal and uterus fat pad weight on a 24 hour access to HFCS,  and this was the group with the most increase in fat pads among the other  groups. In the males, the 12 hour HFCS group had the most increase in fat pads, compared to the females who had a greater increase with the 24 Ad libitum  HFCS availability.

11.Males with access to HFCS gained significantly more weight than the group who  had only chow. This could be because of the sweetness in the chow and their  affinity to the sweetness over the regular chow. Also when HFCS is ingested, it  does not produce a major satiety response so the groups who had access to  HFCS all day would consume more because they felt less full. There could of  definitely been a difference in intake between the two groups because the HFCS  group gained significantly more weight than the group with chow only access.

12.The female group with access to 24 hour HFCS gained significantly more weight  than those with access to sucrose or normal chow. Again, this could be because  of the delayed satiety response and the sweetness of the chow, making the  females want to eat more of the chow with HFCS in it. Also because it is left out  for grazing, they can munch on it whenever they are slightly hungry which adds  calories to the diet and thus resulting in weight gain.

13.I believe that the statement that says “long term access to HFCS in rats lead to  obesity, while sucrose did not” is false. When rats are exposed to different types  of chow and different time periods, they will eat when they are hungry or when it  is available. If the sucrose chow was available 24 hours a day along with normal  chow, I would predict that the rats would chose the sucrose chow over the  normal chow, resulting in an increase in calorie intake. However in this  experiment, long term access to HFCS and sucrose are measured with their  effects on obesity, it is true for this experiment. The rats preferred the HFCS over the sucrose, perhaps because of the sweetness and the availability of the chow.

14.Studies addressed the effects of pure fructose using it to represent the HFCS in  the American diet. HFCS is similar to fructose in a way that it adds calories to the diet and can lead to obesity.

15. In Teff et al in 2004, they used meals of high fructose, not high fructose  corn syrup. However some might argue that HFCS and fructose are very similar,  in the study of Teff et al, they used meals of high fructose, not HFCS.

NFS 243: Advanced Nutrition Exam II Study Guide  Proteins  

∙ What are the “essential” or “indispensable” amino acids?

∙ Compare and contrast the various methods of estimating protein  quality.  

∙ Describe the role of the enzymes Alanine Aminotranferase and  Aspartate Aminotransferase in metabolism.  

∙ Describe the diagnostic importance of serum levels of Alanine  Aminotranferase and Aspartate Aminotransferase.  

∙ Briefly describe the metabolic functions of glutathione.  

∙ Be able to describe the major reactions and products of  phenylalanine, tryptophan, and methionine metabolism.  

∙ What is homocysteine, how is it formed, what are the health  concerns related to elevated serum homocysteine, and what  vitamins play a role in homocysteine metabolism?  

∙ What is Hemoglobin A1c and how is it related to the Maillard  reaction?  

Carbohydrates:  

∙ Know how to name sugars according to their D or L, and alpha or  beta configuration.  

∙ What is a “reducing sugar” and why is this property of some  sugars important in metabolism?

∙ Describe the differences (in terms of location, function, and  regulation by insulin) of the Glucose Transporters, GLUT1, GLUT2,  GLUT4 and GLUT5.  

∙ Describe the differences (in terms of function and regulation)  between hexokinase and glucokinase.  

∙ Describe and cite examples of allosteric, covalent modification,  and enzyme induction regulation of carbohydrate metabolism.  

∙ Describe and compare the metabolic effects of insulin and  glucagon on carbohydrate metabolism.  

∙ How do insulin and glucagon function to regulate glycolysis and  gluconeogenesis via fructose 2,6-bisphosphate.  

Maillard Reaction and Advanced Glycation End-Products:  

∙ Briefly describe the initial steps in the Maillard reaction (through  Amadori rearrangement).  

∙ What are Advanced Glycation End-Products (AGE’s)? Why are AGE’s of health concern?

What are the major differences between the AGE receptors, RAGE and AGE-R1?  

High Fructose Corn Syrup:  

∙ Describe the basic differences and similarities between the  chemical compositions of sucrose, HFCS, pure fructose, and pure  glucose.  

∙ What is the difference between the absorption and metabolism of fructose, as compared to glucose?  

∙ What are the principle issues raised regarding the health effects  of HFCS?

Describe the proposed association between HFCS and increased  de novo lipogeneisis.

∙ Be able to discuss the strengths and weaknesses of the Princeton  study HFCS article discussed in class.  

Lipids:  

∙ How do you name a fatty acid using the “omega’ system and the  “delta” system? What is a “pentadiene system” and why is it  important in lipid peroxidation? Describe the processes by which  dietary fats are digested and absorbed.

What is the rate-limiting enzyme in cholesterol biosynthesis?  

∙ Be able to briefly describe how statin drugs have anti inflammatory properties.  

Terms to Know:  

∙ Peptide bond Chemical Score Aminotransferase Glutathione  

∙ Pancreatic amylase Sucrose

Reducing sugar GLUT4 Glycogenolysis Glucokinase Glucagon  Phosphofructokinase  

∙ Amadori compound AGE-R1  

∙ Linoleic acid

Stearic acid Eicosapentaenoic acid Pentadiene system  Phospholipid

Orlistat (Alli, Xenical)  

∙ Essential amino acids Biological Value Carnitine

ALT and AST  

∙ Maltose Aldose GLUT1 GLUT5 Glycolysis Hexokinase Epinephrine  NADH

∙ Carboxymethyl Lysine  

∙ Palmitic acid

Linolenic acid Docosahexaenoic acid Fatty acid peroxidation HMG  CoA Reductase Micelle  

∙ Protein Efficiency Ratio Net Protein Utilization Creatine  Homocysteine  

∙ Lactose

Ketose

GLUT2 Glycogenesis Gluconeogenesis insulin  

∙ Uric Acid RAGE  

∙ Oleic acid Arachidonic acid Omega-3 fatty acid  

∙ Pancreatic lipase

NFS 243: Advanced Nutrition Exam II Study Guide  Proteins  

∙ What are the “essential” or “indispensable” amino acids? (Red  are totally indispensable)  

o T – threonine

o T - tryptophan

o M – methionine  

o I – isoleucine  

o L – leucine  

o L – lysine  

o V – valine  

o P – phenylalanine  

o H – histidine  

∙ Compare and contrast the various methods of estimating protein  quality.  

o Video  

∙ Describe the role of the enzymes Alanine Aminotranferase (ALT)  and Aspartate Aminotransferase (AST) in metabolism.  

∙ Describe the diagnostic importance of serum levels of Alanine  Aminotranferase (ALT) and Aspartate Aminotransferase (AST)

o Liver disease = high AST and ALT

o Heart Muscle: normally high in AST and low in ALT, if blood  is high in AST then indicates a heart attack – death of heart  tissue  

∙ Briefly describe the metabolic functions of glutathione.  o Glutathione plays a role in leukotriene biosynthesis  o It is used in the process of eliminating toxins from the body  Phase 1 and phase 2 metabolism  

o Protects cells form free radical and peroxide damage  o

∙ Be able to describe the major reactions and products of  phenylalanine, tryptophan, and methionine metabolism.  

∙ What is homocysteine, how is it formed, what are the health  concerns related to elevated serum homocysteine, and what  vitamins play a role in homocysteine metabolism?  

∙ What is Hemoglobin A1c and how is it related to the Maillard  reaction?  

Carbohydrates:  

∙ Know how to name sugars according to their D or L, and alpha or  beta configuration.  

∙ What is a “reducing sugar” and why is this property of some  sugars important in metabolism?  

∙ Describe the differences (in terms of location, function, and  regulation by insulin) of the Glucose Transporters, GLUT1, GLUT2,  GLUT4 and GLUT5.  

∙ Describe the differences (in terms of function and regulation)  between hexokinase and glucokinase.

∙ Describe and cite examples of allosteric, covalent modification,  and enzyme induction regulation of carbohydrate metabolism.  

∙ Describe and compare the metabolic effects of insulin and  glucagon on carbohydrate metabolism.  

∙ How do insulin and glucagon function to regulate glycolysis and  gluconeogenesis via fructose 2,6-bisphosphate.  

Maillard Reaction and Advanced Glycation End-Products:  

∙ Briefly describe the initial steps in the Maillard reaction (through  Amadori rearrangement).  

∙ What are Advanced Glycation End-Products (AGE’s)? Why are AGE’s of health concern?

What are the major differences between the AGE receptors, RAGE and AGE-R1?  

High Fructose Corn Syrup:  

∙ Describe the basic differences and similarities between the  chemical compositions of sucrose, HFCS, pure fructose, and pure  glucose.  

∙ What is the difference between the absorption and metabolism of fructose, as compared to glucose?  

∙ What are the principle issues raised regarding the health effects  of HFCS?

Describe the proposed association between HFCS and increased  de novo lipogeneisis.  

∙ Be able to discuss the strengths and weaknesses of the Princeton  study HFCS article discussed in class.  

Lipids:

∙ How do you name a fatty acid using the “omega’ system and the  “delta” system? What is a “pentadiene system” and why is it  important in lipid peroxidation? Describe the processes by which  dietary fats are digested and absorbed.

What is the rate-limiting enzyme in cholesterol biosynthesis?  

∙ Be able to briefly describe how statin drugs have anti inflammatory properties.  

Terms to Know:  

∙ Peptide bond Chemical Score Aminotransferase Glutathione  

∙ Pancreatic amylase Sucrose

Reducing sugar GLUT4 Glycogenolysis Glucokinase Glucagon  Phosphofructokinase  

∙ Amadori compound AGE-R1  

∙ Linoleic acid

Stearic acid Eicosapentaenoic acid Pentadiene system  Phospholipid

Orlistat (Alli, Xenical)  

∙ Essential amino acids Biological Value Carnitine

ALT and AST  

∙ Maltose Aldose GLUT1 GLUT5 Glycolysis Hexokinase Epinephrine  NADH  

∙ Carboxymethyl Lysine  

∙ Palmitic acid

Linolenic acid Docosahexaenoic acid Fatty acid peroxidation HMG  CoA Reductase Micelle

∙ Protein Efficiency Ratio Net Protein Utilization Creatine  Homocysteine  

∙ Lactose

Ketose

GLUT2 Glycogenesis Gluconeogenesis insulin  ∙ Uric Acid RAGE  

∙ Oleic acid Arachidonic acid Omega-3 fatty acid  ∙ Pancreatic lipase

NFS 243: Advanced Nutrition Exam II Study Guide  

Proteins  

∙ What are the “essential” or “indispensable” amino acids? (BLUE are  totally indispensable)  

 They are amino acids that are not made within the body or  are not made in significant enough amounts so they need  to be consumed  

o T – threonine

o T - tryptophan

o M – methionine  

o I – isoleucine  

o L – leucine  

o L – lysine  

o V – valine  

o P – phenylalanine  

o H – histidine  

∙ Compare and contrast the various methods of estimating protein  quality.  

o Chemical or amino acid score  

 Score = (limiting AA in food protein / content of AA in  

reference protein) x 100

 Limiting amino acid = essential amino acid in the smallest  amount in comparison to reference point

o Protein efficiency ratio  

 PER = gain in body weight (grams) / protein consumed  (grams)  

 FDA approved for determining daily values in infant  formulas  

 Higher protein quality, LOWER DV

 Takes less high quality protein to support growth than low  quality  

 Used under standardized conditions

 Biological

 Most used  

o Biological value  

 BV = (nitrogen retained / nitrogen absorbed) x 100

 Takes into account nitrogen lost in feces and urine

 Poorer the protein, more nitrogen excreted in urine  

 Used in studies

 Biological  

o Net protein utilization (NPU)  

 NPU = [nitrogen retained / nitrogen consumed) x 100  Takes in account total carcass in nitrogen  

 Used in studies

 Biological  

∙ Describe the role of the enzymes Alanine Aminotranferase (ALT) and  Aspartate Aminotransferase (AST) in metabolism.

o ALT and AST play a role in transamination reactions. Great  diagram. You have an alpha-keto acid, alanine becomes pyruvate using ALT. vitamin required for these reactions is = B6! With AST, the alpha-keto acid becomes aspartate, and you have the  apoxoiloacid that is formed. Check out the slide. AST goes to  oxaloacetate with the help of B6.  

∙ Describe the diagnostic importance of serum levels of Alanine  Aminotranferase (ALT) and Aspartate Aminotransferase (AST)

o Liver disease = high AST and ALT as well as other enzymes   Elevated levels are BAD  

 Liver damage due to infection or something else  

o Heart Muscle: normally high in AST and low in ALT, if blood is  high in AST then indicates a heart attack – death of heart tissue  

 Heart muscle is higher in AST, so when levels are low it  means the death of the heart tissue, indicating a heart  

attack  

 Troponin, LDH-1, CK-MB, glycogen phosphoralase  

∙ All better markers for heart attack  

∙ Briefly describe the metabolic functions of glutathione.  o Glutathione is a tripeptide  

o Glutathione plays a role in leukotriene biosynthesis

 LTA4LTC4 (adds glutathione side chain)  

 Involved in the inflammation response  

o It is used in the process of eliminating toxins from the body  Phase 1 and phase 2 metabolism  

o Assists in amino acid transport  

o Prevents free radical and peroxide damage

o Acts as an antioxidant  

o Superoxide’s – produced intentionally from oxidative  phosphorylation, these have to be broken down. Or else they can form more damaging compounds such as hydroxyl radicals. This  is where superoxide dismutase comes in. this functions by  converting Superoxide’s to Hydrogen Peroxide. Peroxidases /  catalases that break down the peroxides to water. Glutathione  peroxidase, glutathione dependent enzyme for breaking down  peroxide to water.

o GSSH (glutathione in it’s reduced form) forms oxidized form  GSSG.  

 Glutathione with GSSH makes peroxide H2O and oxygen.   This REQUIRES selenium. This is the oxidized form of  

glutathione, which is known as GSSG. Your body needs to  regenerate glutathione into its reduced form which  

involves glutathione reductase and this involves  

riboflavin. 

o Eliminates toxins from the body

 Glutathione S transferase, is a phase 2 metabolic enzyme.  This allows toxins to be excreted. Forms a toxin GSH  

conjugate, and then that’s what gets excreted in the urine.  So toxin, phase 1 metabolism occurs which converts it to  it’s carcinogenic form, BAD FORM, then there’s an oxidized  toxin intermediate, than phase 2 happens and glutathione  transferase comes into play and creates the GSH conjugate which you then pee out  

∙ Be able to describe the major reactions and products of phenylalanine,  tryptophan, and methionine metabolism.  

o Phenylalanine, Iron containing enzymes that need to be in  reduced form. Vita C plays a role because it keeps iron in its  reduced form for phenylalanine to be able to convert it to  tyrosine. And once it makes it to tyrosine it can make  

catecholamine’s, etc.  

o Tryptophan, can be converted to serotonin. This plays a role in GI motility and contractions. Serotonin can be converted to  melatonin which regulates sleep cycles, circadian rhythm. From  there it can form many intermediates. Cascade reactions. This  pathway can lead to the production of NADPH along with NAD.

Important to remember its glucogenic, can help with glucose  synthesis.  

o Methionine can go through a number of steps to produce  cysteine. It reacts with ATP and is converted to S-adenecyl  methionine, which functions as a methyl donor. And once it gives up its methyl group its converted to asa-dencyl-homocysteine.  So now it can lose an andeycel group and become homocysteine  which can go back to form methionine cysteine.  

∙ What is homocysteine, how is it formed, what are the health concerns  related to elevated serum homocysteine, and what vitamins play a role in homocysteine metabolism?  

o Homocysteine is involved in heart and vascular diseases.  Methionine is a sulfur containing amino acid, it can act as a  source of cysteine. The meta-analysis, of disease risk and  homocysteine levels. One about stroke and hystemia. Bottom  line, increased levels of homocysteine levels in blood lead to this  heart disease. Risk for heart disease was lower as homocysteine  was lower. But NOTE, this is only an association, NOT causal. B  vitamins are important. Note, B12 6 and Folate are important to  this pathway.  

∙ What is Hemoglobin A1c and how is it related to the Maillard reaction?  

o Aldehydes are likely to react with amines. Which is the maillard  rxn. Glucose is a reducing sugar that can react with the amines,  including hemoglobin which is an amine and other things that  are present in the blood tissue. And this happens and it forms  these non-enzymatic reactions that occur in our bodies.  Hemoglobin A1C has a glucose attached, ligated hemoglobin it  goes by. This is bc when the levels of glucose are elevated,  they’re more likely to react with proteins in the blood. To glucose  is likely to react with the amines. A1C, 80% of the glucose binds  to the lysine groups of hemoglobin. So this is why diagnostically,  A1C is used to monitor glucose control in diabetes. Better than  measuring glucose in the blood bc that reflects hour to hour  changes whereas A1C is a better indicator as to how blood  glucose is controlled over time. When glucose binds to  

hemoglobin, it binds irreversibly. This is typically of aldehyde  amine reactions. This can measure blood glucose over long  periods of time, lifespan of the RBC = 120 days. Although A1C is  a good marker for glucose control the underlining issue is that  when glucose levels are elevated it can react with other proteins  as well. So it can ligate many other proteins as well. Like

conditions associated with diabetes like blood vessel damage,  damage to vessels in eye, has to do with glucose reacting with  other proteins in the blood and that causes this damage. And  that’s A1C.  

o When glucose binds to hemoglobin at lysine residues  

o Good indicator of long-term glucose control  

 Once binds glucose, cannot be removed from hemoglobin.  Bound until cell dies  

o Protein that’s measured in diabetics to monitor glucose control o Relation to maillard rxn  

 Terminal amine group of hemoglobin binds aldehyde on  glucose just like methylglyoxal and formaldehyde with  

ammonia in the maillard rxn  

Carbohydrates:  

∙ Know how to name sugars according to their D or L, and alpha or beta  configuration.  

o Gotta watch the video. Watch the podcast. This will probably be a multiple choice question  

∙ What is a “reducing sugar” and why is this property of some sugars  important in metabolism?  

o A reducing sugar is a sugar that is capable of opening up to form  a free ketone or free aldehyde in solution thus allowing it to react with other compounds like amines. All monosaccharaides are  reducing sugars. Sucrose is a NON-reducing sugar because it’s  carbonyl carbons are tied up in the linkages. In metabolism, we  know glucose only a small % exists in it’s free aldehyde form.  Different sugars exist in diff % in the blood, glucose was the  lowest %, so this is why other sugars in the blood don’t go  through the maillard rxns. Aldehydes and ketones = bad this is  what causes problem with diabetes and problems to blood

vessels. So more sugar = bad because more rxns which cause  more problems. But if they’re too elevated this is the  

complications.  

o Glucose is THE sugar in our blood because the other ones get  sent to liver or somewhere to get broken down because if they  went into the blood stream like glucose does they would cause  reactions that cause problems.  

∙ Describe the differences (in terms of location, function, and regulation  by insulin) of the Glucose Transporters, GLUT1, GLUT2, GLUT4 and  GLUT5.  

o Memorize the glut transporters.  

o GLUT1: regulated by insulin: No, location: blood brain barrier,  placenta, fetal tissues, erythrocytes, function: basic supply of  glucose to enterocytes and ethelial cells of the brain and most  tissues  

 Cannot bind carrier until sodium binds  

 Unidirectional important  

o GLUT2: regulated by insulin: No, location: liver, pancreatic beta  cells, kidney, small intestine, function: glucose and galactose are transported into the enterocytes by GLUT2 via facilitated  transport, fructose leaves the cell using GLUT2.

 Glucose across the basolateral side into bloodstream

 Transports fructose across basolateral side of cell  

o GLUT4: regulated by insulin: YES, location: brown and white  adiposities, heart and skeletal muscle, function: as glucose rises,  the pancreas senses this and stimulates release of insulin in the  blood stream which helps regulate glucose in the blood and  causes glucose homeostasis. Insulin in the blood stream then  binds to the extracellular domains of the receptor proteins found  on the surface of liver, muscle and fat cells. This binding triggers  the intracellular phosphorylation of the intracellular domains  which in turn phosphorylates a substrate and this leads to a  signal transduction cascade and you need to know that this  cascade, the movement of glucose transporters to the surface of  the cell. So as these storage vesicles move they bind to the cell

membrane, this causes more GLUT transporters that are on the  surface and this allows glucose to enter the cell. [] of glucose in  the cell rises, and this allows ATP to be formed in the cell.  

 NOT IN THE LIVER

o GLUT5: regulated by insulin: NO, location: small intestine,  function: important transporter for fructose. Important because  fructose enters the enterocyte through facilitated transport by  GLUT5, but it leaves the cell through GLUT2. So fructose requires  2 different GLUT, keep that in mind.  

 Glucose enhances GLUT5

∙ Describe the differences (in terms of function and regulation) between  hexokinase and glucokinase.  

o We’re thinking of the conversion of glucose to glucose-6- phosphate. So this can happen through hexokinase or  

glucokinase.  

o Hexokinase functions primarily through the tissues. So it has a  lower KM, which means it has a higher affinity for glucose. This is important for the tissues. Because it’s very sensitive to glucose  levels because our muscles are a priority for glucose. So since it  has a lower KM, it can grab glucose very quickly.  

 In MUSLCE, not liver  

 Converts glucose to gluc-6-phos in muscle  

 Higher affinity for glucose , lower KM = higher affinity   Lower Vmax  

 Muscle grabs glucose even when glucose [] isn’t that high – bc muscles need ATP to do work (ex. heart)  

 NOT induced by insulin  

o Glucokinase functions in the liver. It has a higher KM, which  means it has a lower affinity for glucose. This takes more glucose to reach it’s max. so because it has a high VMAX the capacity for  it to grab a lot, this makes the liver good for controlling it even

though it goes slowly. Because it’s able to stable it better  because the high VMAX.  

 Converst glucose to gluc-6-phos in liver

 Low affinity for glucse, HIGH Km = low affinity  

 HIGH Vmax

 Metabolize more glucose at a higher rate  

o In terms of enzyme regulation, it’s important to know that  glucokinase, it’s inducible by insulin. So in a response to a meal,  when insulin levels go up, insulin will induce glucokinase.  

∙ Describe and cite examples of allosteric, covalent modification, and  enzyme induction regulation of carbohydrate metabolism.  

o Allosteric: can stimulate or suppress the enzymatic activity of a  pathway. Is said to be either positively or negatively modulated.  AMP, ADP, and ATP can act as allosteric modulators. These are an indication of the energy status of a cell, important regulatory  factor in energy metabolism. So if, ATP is abundant, so enough  energy in a cell, and ADP is scarce, we know that no energy is  needed. So pathways that create ATP are negatively modulated,  so they reduce ATP production because you don’t need it.  Whereas, is ADP or AMP is abundant and ATP is low, it shows  depletion of ATP and more energy is needed. So the AMP or ADP  positively stimulates the energy releasing pathways. Take home  message, ADP, AMP, ATP can act as allosteric regulators  depending on the energy needs. NADH, NAD ratio. As we know,  NADH is a product of glycolysis, so it’s build up indicates that the pathway is not needed to create additional ATP. Whereas is  NAD+ or NAD, we know oxidative steps in glycolysis would be  favored. So a high NAD:NADH = WE NEED ENERGY. This happens  when liver is in a fasted state, can produce more glucose through gluconeogenesis.  

o Covalent: adding or removing phosphates via kinases and  phosphatases.  

 Ligand binds receptor and causes conformational change in G protein. cAMP made which activates internal signal and  regulates enzyme activity

 Phosphorylation of PFK2 or FBP2 in hormonal regulation of  carb metabolism  

o Enzyme induction

 Increases in protein synthesis to stimulate production of  enzymes  

∙ Describe and compare the metabolic effects of insulin and glucagon on carbohydrate metabolism.  

o Insulin: anabolic hormone, storage of energy. Insulin = STORAGE. And processes that increase the synthesis of glucose  

 Inhibit glycogenolysis in muscle of liver – stops the  

breakdown of glycogen & Inhibit gluconeogenesis  

∙ Glycogenolysis = break glycogen down to glucose  

∙ Gluconeogenesis = making glucose  

 Hormone sensitive lipase (intracellular lipase – breaks  down triglycerides to free FA so they can be used to make  energy ) release free FA for energy, inhibit adipose tissue  to break down energy

 Induces lipoprotein lipase  

∙ Lipoprotein taken from blood and stored in adipose to synthesize triglycerides and store them  

 Increase GLUT4 transporters in muscle and adipose tissue

 Stimulates amino acid uptake and protein synthesis in  most tissues (but not he liver)  

 Increase glucose synthesis

∙ Liver and muscle gluconeogenesis

o Glucagon – acts as the opposite of insulin, so this is a catabolic  hormone (breaks down glycogen in liver to get glucose)  

 Increases glycogenolysis  

 increases gluconeogenesis  

 activates lipolipase in adipose tissue – goal is to release  energy from adipose tissue

∙ lipolysis – fatty acids are used to make hormones  

 NOT IN MUSCLE  

 increase amino acid uptake in liver

∙ provides the carbon skeleton in gluconeogenesis  

∙ How do insulin and glucagon function to regulate glycolysis and  gluconeogenesis via fructose 2,6-bisphosphate.  

o Slide for the pathway – KNOW & go over the notes  

o Like PKF-1

o On cell membrane, there are receptors for insulin and glucagon  o Fructose-6-phosphate to fructose-6-bisphosphate  

o Bifunctional enzyme – two catalytic capabilities  

o PFK-2 and FBP-2 in phosphorylated form  

 PFK-2 : inactive

 FBP-2: active  

∙ In dephosphorylated form: the inactive and active  

are opposite

Insulin: when HIGH and glucagon is LOW, decrease cyclic cAMP production  (positive allosteric regulator of protein kinase) – so lower levels for protein  kinase. This INHIBITS phosphorylated bifunctional enzyme, so more in the  

dephosphorylated form. Results in PFK-2 ACTIVE form. And covert fruc-6-phos to fruc-2,6-bisphos and this is a POSITIVE ALLOSTERIC MODULATOR of PFK-1.  Once PFK-1 is activated, stimulates fruc-6-phos to fruc-1,6-bisphos. Allows  glycolysis to go in the right direction. Stimulates the conversion of fruc-6- phos to fruc-1,6-bisphos by PFK-1 (this is the irreversible step)  

Fructose  fructose 1,6 BP is the rate limiting step (irreversible)  Glycolysis – able to go in the right direction now because of these rxns  

Glucagon: HIGH levels of glucagon (hypoglycemia) and LOW insulin. Results  in stimulation of cyclic AMP. cAMP activated protein kinase and protein kinase phosphorylates. So this favors phosphorylation of bifunctional enzyme. So  PKF-2 is INACTIVE and FBP-2 is ACTIVE. When FBP-2 is active, it favors the  dephosphorylation of fruc-2,6-phos to fruc-6-phos which leads to LESS fruc 2,6-bisphos and when less F-2,6-BP  the reserve rxn is favored.  

Maillard Reaction and Advanced Glycation End-Products:  

∙ Briefly describe the initial steps in the Maillard reaction (through  Amadori rearrangement).  

o Reducing sugars like glucose like to react to form brown pigment, and can happen in bodies

o The initial steps are important  

o Know that protein has amine group and a reducing sugar can  react with this protein, the early steps are REVERSIBLE  

o Glucose reacts with amine group from protein, creates a   Schiff base and  

 rearrangement of the double bond (Amadori product)

 Amadori rearrangements is the first IRREVERISBLE step,  first step that you CANNOT form an amino acid anymore  

∙ Amadori shifts where double bond is

∙ Once Amadori step is formed, new aines can react to  make new compounds  

∙ Malanoids = brown pigments that form at the end of  maillard reaction  

∙ What are Advanced Glycation End-Products (AGE’s)

o AGES: formed in vivo, maillard rxn  

o Aldehyde reacts with amines, comes from ___ and lysine.  Depending on how much lysine there is will depict if a rxn will  occur. Size of protein and how much lysine is available is  important.  

o End products of maillard rxn (not pigments but other compounds  formed after Amadori compound)

o Associated with aging and chronic disease (type-2 diabetes, CVD) o They accumulate over lifetime  

∙ Why are AGE’s of health concern?

o High levels are associated with aging, non-pathologial aging. T2D and CVD,  

o vascular damage – sugars bind proteins that result in less  elasticity, normal turnover of blood vessels slow down  

o oxidative stress – more reactive oxygen species are produced  when AGE’s react with a cell  

o oxidation of LDL – which causes plaque formation and promotes  atherosclerosis  

o secrete pro-inflammatory cytokines

o Highly correlated with diet. Foods high in AGE contribute to  amount in vivo.

o Such as anything that is grilled / fried (high AGE diet)

o Reduce exposure to AGE by eating more boiled, poached, etc.  (low AGE diet)

o Damage happens when proteins that line blood vessels are  damaged  

∙ What are the major differences between the AGE receptors, RAGE and  AGE-R1?  

o RAGE: negative consequences of AGE in cell, results in pro inflammatory gene activation, pro-inflammatory cytokines,  reactive oxygen species (ROS)

 Makes the problems WORSE

 When AGE binds RAGE, NK-kB is activated and pro

inflammatory cytokines are produced (IL-Ioc)

o AGE-R1-: plays role in removal of AGE, such as AGE endocytosis  and degradation, enhances insulin receptor activity and  

surpasses oxygen species  

 Makes the problems BETTER

 Plays a role in the REMOVAL of advanced glycation end  products  

 Suppresses ROS  

High Fructose Corn Syrup:  

∙ Describe the basic differences and similarities between the chemical  compositions of sucrose, HFCS, pure fructose, and pure glucose.  

o Sucrose: 50% fructose, 50% glucose.  

 Mixture of these two that can be broken down to form two  monosaccharide’s.

 HFCS and sucrose are essentially the same  

o HFCS: made of 55% fructose, 45% glucose.  

 Can form fructose and glucose.  

 No different than other caloric sweetners  

 Doesn’t cause obesity or diabetres more than other sugars   Causes small rise in uric acid

∙ Not enough to cause diabetes  

o Pure Fructose: simple sugars. Monosaccharide.  

 Chemical formula is the same but different  

rearrangements, fructose is a ketohexose.  

 Intake causes rise in uric acid  

 Doesn’t exist in normal nature  

 Pure fructose causes lipogenesis, but HFCS does not   Causes problems while sucrose does not  

 GLUT5 transports fructose across apical side and does not  work well when there is no glucose.  

∙ So GI stress occurs  

o Pure glucose: aldohexose (don’t really need to know much)

∙ What is the difference between the absorption and metabolism of  fructose, as compared to glucose?  

o Wall of small intestine is lined with highly absorptive cells – villi  and such. Microvilli increase surface area and facilitate  

absorption of these sugars.  

o Glucose

 Absorption: active transport gets into the enterocyte by  active transport. Active transport requires ATP and sodium

and SGLT-1 to get across apical membrane. Sodium and  glucose go in the same direction. So glucose needs sodium attachment. Sodium increase affinity of transport protein  for glucose to get inside the side. Glucose is then released  into the cell and sodium ion is pumped back out of the cell.

 Facilitative diffusion happens when glucose levels are high  to get into the enterocyte by GLUT2 receptors  

 GLUT1 (sodium glucose transporter) transports glucose  across apical side of the cell  

 GLUT1 needs to bind sodium before it can bind glucose  

∙ Affinity for glucose to bind increases after sodium  

binds to transporter

∙ Unidirectional import  

o Fructose  

 Getting into the cell by GLUT5. Primary into the mucosal  cell is by facilitative transport of GLUT5.  

 Uptake of fructose is a lot slower than that of glucose of  galactose, but increased when GLUT2 Is present on the  apical membrane as well as the basal side

 GLUT2 transport out of the enterocyte into the portal vein  (the same as glucose)  

 Doesn’t end up in the blood

 Processed in liver immediately  

 Absorption of fructose results in less glucose output from  the liver which is why glucose goes down when fructose  goes up  

∙ What are the principle issues raised regarding the health effects of  HFCS?

Describe the proposed association between HFCS and increased de  novo lipogeneisis.  

o 5 different arguments

 HFCS contains ketose sugars in open chain form in a lot  higher [] than glucose. Fructose intake reduces blood  plasma glucose levels  thought that HFCS exposes us to  reactive carbonyls is dismissed **KNOW THIS EXAMPLE**

 HFCS can lead to fructose intolerance  

∙ Type 1 fructose intolerance : hereditary fructose  intolerance  

o Genetic deficiency in Aldolase B which converts fruc-1-phos to glyceraldehyde and DHAP

o Traps fruc-1-phos in liver and can cause hepatic failure and death  

∙ Type 2 fructose intolerance: malabsorption of  fructose from GI tract  

o GLUT5 transports fructose across apical side as long as glucose is present  

o Can only occur if consume large amounts of  pure fructose which is not realistic with HFCS  

bc its 50/50 glucose/fructose  

 HFCS can stimulate lipogenesis (accumulation of fat in the  liver)

∙ If PFK1 is bypassed, a lot of NADH is made, ATP  increases. NADH inhibits the Krebs cycle and citrate  builds up. Citrate positively allosterically modulates  acetyl coA carboxylase (the rate limiting enzyme in  fatty acid synthesis)  

∙ Overall idea: the more citrate builds up, the more  fatty acids are synthesized  

 HFCS increases uric acid production (do not know pathway) and decreases nitric oxide functionality  

 HFCS does not stimulate insulin and leptin release and  increased de-novo lipogenesis.

∙ Know proposed association between HFCS and increased de novo  lipogenesis

o PSK if the rate-limiting enzyme in glycolysis. A lot of NADH and  ATP are made and NADH builds up and inhibits Krebs cycle.  Citrate builds up. An increase in citrate causes an increase in  lipogenesis because it positively allosterically modulates acetyl  coA carboxylase (the rate limiting enzyme in fatty acid synthesis) so more fatty acids are synthesized. The extra fatty acids are  then stored.  

Discuss strengths and weaknesses of Princeton study HFCS article discussed  in class  

∙ Be able to discuss the strengths and weaknesses of the Princeton  study HFCS article discussed in class.  

o Measured intake daily and body measurements weekly. There  can be a lot of error here.  

o Took in less calories from HFCS but HFCS group gained more  weight **the sucrose group exercised more**

o No total difference in total calorie intake  

o claim: rise in obesity is linked to rise in HFCS consumption  o Teff. Et al gave women doses of fructose, not HFCS

o Article argues HFCS is different from sucrose  

o Took away sucrose control group in 2nd study. Need control to  compare to in order to make conclusions  

o Did 24 hour HFCS trial, but didn’t do a 24 hr sucrose trail  

o Basically BFCS does not = fructose, so these trials need to get  their stuff together and stop making false claims

Lipids:  

∙ How do you name a fatty acid using the “omega’ system and the  “delta” system?  

o Delta System  

 Begin at carbocyclic acid (usually on right) and count  carbons. Total # carbons; total # double bonds delta  

positions of double bonds  

 Double bonds are ALWAYS on 3rd carbon  

o Omega System

 Start at methyl end (usually left side) and count carbons.  Total #carbons; total # double bonds omega position of  

bond – or – n position of bond  

o Essential fatty acids you need to get in the diet  

 Essential bc humans cant add double bonds beyond the  delta-9 position  

 We lack enzyme delta-12-desaturase and delta-15-

desaturase  

 Palmitic 16:0 SATURATED  

 Stearic 18:0 SATURATED  

 Oleic 18:1

 Linoleic 18:2, ESSENTIAL precursor to many other fatty  acids like arachidonic acid  

 Linoleic 18:3 ESSENTIAL

 Arachidonic 20:4

 EPA 20:5, omega-3

 DHA 22:6, omega-3

∙ What is a “pentadiene system” and why is it important in lipid  peroxidation?  

∙ Pentadiene system = 5 carbon unit with two double bonds o Target for where oxidation occurs, so more pentadiene  systems, more susceptible to oxidation the compound is  Arachidonic acid is very susceptible to oxidation  

because it has a lot of pentadiene systems

 Adding a double bond increases sensitivity to oxidation  Fatty acids typically have double bonds separated by 3  carbons

∙ 1. Pentadiene system

∙ 2. Initiation: middle carbon of pentadiene loses an electron and turns  into a free radical  

o takes a complete fatty acid and turns it into a free radical o UV light, heat and metal catalysts can increase initiation  (rancidity of oils)

o Chelating agents (such as citric acid, EDTA): added to foods to  prevent lipid oxidation by binding metals

∙ 3. Double bond shifts so free radical can be in different places o Fatty acid free radical exists as a conjugated double bond  system (alternating double and single bonds), which is more  stable than non-conjugated resonance hybrid free radical and  therefore present in higher amounts.

∙ 4.conjugated double bond system fatty acid free radical reacts with  oxygen to form a peroxy free radical

∙ 5. Propagation: peroxy free radical reacts with a fatty acid and  removes an electron from the fatty acid to make a fatty acid peroxide  (which is no longer a free radical)

o starts a chain reaction because fatty acid that electron is  removed from is now a free radical and can go through initial  steps of oxidation

o can limit oxidation exposure by flushing packages with nitrogen ∙ 6. Rancid degradation products are formed

o fatty acid peroxide starts to break up into aldehydes and  ketones that give off bad flavor and aroma

o MDA (malon dialdehyde) = used to measure degree of rancidity  in oil and in vivo

∙ 7. Termination: where vitamin E would act. Prevents propagation. o Only occurs if antioxidant (such as vitamin E) is there o Aldehydes are produced as result of fatty acid oxidation  and then react with amines in maillard reactions

o Cholesterol esters = cholesterol compounds esterified to a  fatty acid compound

∙ Ways to prevent lipid oxidation

o 1. Chelating agents prevent initiation

o 2. Nitrogen packages prevent reaction with oxygen

o 3. Antioxidants prevent propagation by donating an electron  instead of pulling an electron from another fatty acid and  creating a new free radical

o 4. Vitamin E becomes a weak free radical and stabilizes itself o 5. BHA and BHT = artificial chemicals that stop propagation by  acting like antioxidant

∙ Describe the processes by which dietary fats are digested and  absorbed.

o No digestion of fats occurs until they reach the small intestine ∙ Bile acids are used to emulsify lipids so that they can be  absorbed

∙ Pancreatic Lipase cleaves fatty acids off of triglyceride in the  small intestine

∙ Cholesterol is typically bound to fatty acids

o Cholesterol esterase cleaves the fatty acid off of  

cholesterol to create free cholesterol

o Phosphatidyl choline = a phospholipid with 2 fatty acids  removed by lipase

o Triacylglycerol can have 2 fatty acids cleaved off by  

pancreatic lipase to get 2 monoacylglycerol

∙ Bile acids/ bile salts (ex. Cholic acid)

o Synthesized by cholesterol in the liver

o Stored in gallbladder

o Bile salt = bile acid conjugated with glycine or taurine  Glycine is put on where carboxylic acid was

o Good emulsifiers because part polar and part non polar o 90% of bile acids and bile salts are recovered in small intestine  back to the liver

∙ Unstirred water layer = water protective layer before material can get  into enterocyte.

o Lipids need to be carries across by micelle

∙ Micelle= digested fatty acids and cholesterol surrounded by bile salts  and phospholipid

o Nonpolar faces in and polar faces out

o Micelle diffuses through water layer (apical side) and then  releases contents so they can diffuse through bilayer and into  enterocyte

o Low chain length pass easily into portal circulation and don’t  need micelle

∙ Chylomicron = lipoprotein that contains protein, phospholipids,  cholesterol and triglycerides

o Has A LOT of triglyceride- picks up all dietary fat from the  intestine

o ONLY produced in the intestine

o Carries across basolateral side the general circulation via the  lymphatic system

∙ Serum: let blood clot, centrifuge it and RBCs pack at bottom, clotted  material in the middle and then serum on top.  

o Soluble part of blood

o Serum will be cloudy after eating a fatty meal

∙ Weight loss drugs

o Olestra (sucrose polyester)

 Glucose and fructose added to fatty acid

 Body lacks the enzyme to cleave fatty acids off from  

sucrose, so fats pass through the digestive tract  

unabsorbed

 Causes anal leakage if eat a large amount of fat- fatty acid  oils leak out

o Orlistat (Xenical, Alli)

∙ Pancreatic lipase inhibitor

o Pancreatic lipase = lipase produced by pancreas that  

digests fat

o If pancreatic lipase is inhibits, won’t be able to break  

down fat and it will pass unabsorbed

∙ 1.relies on pancreatic lipase

∙ 2. Relies on not eating too much fat

∙ if eat too much fat, anal leakage will occur

∙ Success only if not eating too much fat- MUST eat a  

healthier diet

Cholesterol Sources

∙ 1.dietary cholesterol transported by chylomicrons

∙ 2. Cholesterol synthesized in extrahepatic tissues (HDL) ∙ 3. De novo synthesis in liver

o make bile salts

o deliver cholesterol to other tissues  

How Cholesterol Leaves Liver

∙ 1. Inside VLDL

∙ 2. Bile acids/bile salts

∙ 3. Free cholesterol secreted in bile

Cholesterol Functions

∙ 1. Produce sex hormones

o progesterone, testosterone, estradiol

∙ 2. Adrenal gland makes corticosteroids

∙ 3. Make bile salts/bile acids (cholic acid) in liver

∙ 4. Make vitamin D3 when exposed to UV light

∙ 5. Important in lipid bilayer fluidity

o membrane structure/function

o

∙ What is the rate-limiting enzyme in cholesterol biosynthesis?  

o HMG coA reductase

o Converts HMG coA to mevalonate

o Cholesterol can have negative feedback on HMG coA reductase  As more cholesterol is made, HMG coA reductase is  

inhibited

o Statin drugs compete for reaction with HMG coA reductase to  inhibit the enzyme

 Statin drug structure is similar to HMG structure, so  

compete for active site on HMG coA reductase

 Reduced HMG coA reductase activity means less  

cholesterol is made

 Statin drugs also lower blood lipids, have anti-inflammatory response

∙ Be able to briefly describe how statin drugs have anti-inflammatory  properties.  

∙ Statin drugs produce an anti-inflammatory response which prevents  atherosclerosis  

∙ Mevalonate is involved in inflammation

∙ Farnesyl PP and Geranyl Geranyl PP are derived from isoprenoids (short lipid compounds which are formed from mevalonate that  combine to form Farnesyl PP or Geranyl Geranyl PP)

o They are both intermediates in cholesterol biosynthesis and  they react with RAS proteins

o RAS proteins = G proteins found in membrane  

 Signal protein for outside signal to communicate  

message inside cell

 Plays role in cell proliferation

o Farnesyl PP interacts with Ras protein to make fernesylated RAS  protein

o Farnesyl carries RAS protein to embed it in membrane so  protein can function

o Without Fernesyl PP or Geranyl Geranyl PP, proteins wouldn’t  be able to perform their function (send a signal by binding a G protein)

∙ 1. Geranyl- Geranyl PP binds RAC protein

o 2. RAC protein activates NADPH oxidase

o 3. NADPH oxidase generates oxidative stress

o 4. Oxidative stress causes inflammation by signaling nucleus to  produce pro-inflammatory compounds

∙ Statin drugs reduce the amount of Farnesyl PP and Geranyl-Geranyl PP  which reduces amount of inflammation that occurs

Apoprotein functions

∙ 1. Act as signal ligands that bind receptors on target tissue to signal  how lipoprotein will be metabolized

∙ 2. Structural role in lipoprotein particle

∙ 3. Enzyme activators = enzymes only turned on when certain  apoproteins are on lipoprotein surface so that contents of lipoprotein  will diffuse into target tissue

Terms to Know:  

∙ Peptide bond Chemical Score Aminotransferase Glutathione  

∙ Pancreatic amylase Sucrose

Reducing sugar GLUT4 Glycogenolysis Glucokinase Glucagon  Phosphofructokinase  

∙ Amadori compound AGE-R1  

∙ Linoleic acid

Stearic acid Eicosapentaenoic acid Pentadiene system Phospholipid Orlistat (Alli, Xenical)  

∙ Essential amino acids Biological Value Carnitine

ALT and AST

∙ Maltose Aldose GLUT1 GLUT5 Glycolysis Hexokinase Epinephrine NADH ∙ Carboxymethyl Lysine  

∙ Palmitic acid

Linolenic acid Docosahexaenoic acid Fatty acid peroxidation HMG CoA  Reductase Micelle  

∙ Protein Efficiency Ratio Net Protein Utilization Creatine Homocysteine  

∙ Lactose

Ketose

GLUT2 Glycogenesis Gluconeogenesis insulin  

∙ Uric Acid RAGE  

∙ Oleic acid Arachidonic acid Omega-3 fatty acid  

∙ Pancreatic lipase

04/15/2015

4/15/15 

4/22/15

4/29/15

Study Guide – Exam II

Proteins:  

1. What are the “essential” or “indispensable” amino acids?   Amino acids that are not made within the body or are not made in  significant enough amounts, so they need to be consumed

2. Compare and contrast the various methods of estimating protein quality.   Chemical or amino acid score

 Score= (limiting AA in food protein/content of AA in reference protein)  x 100

 Limiting amino acid = essential amino acid in smallest amount in  comparison to reference protein

 easiest

 Protein Efficiency Ratio

 PER= gain in body weight (grams)/protein consumed (grams)  FDA approved for determining daily values in infant formulas  Higher protein quality, lower DV

 Takes less high quality protein to support growth than low quality  Used under standardized conditions

 Biological

 Most used

 Biological Value

 BV= (nitrogen retained/nitrogen absorbed) x 100

 Takes into account nitrogen lost in feces and urine  

 Poorer the protein, more nitrogen excreted in urine

 Used in studies

 biological

 Net protein Utilization (NPU)

 NPU= (nitrogen retained/nitrogen consumed) x 100

 Takes into account total carcass nitrogen

 Used in studies

 biological

3. Briefly describe the various metabolic fates for amino acids.   Anabolically used

 Protein synthesis

 Synthesis of nitrogen containing compounds

 Catabolically broken down

 Amino group cleaved of

 Amine group excreted in urine

 Amine group used to make non-essential AA

 Carbon skeleton used after amine group cleaved of

 Used to make glucose

 Used for energy

 Used to make fatty acids

4. Describe the role of the enzymes Alanine Aminotranferase and Aspartate  Aminotransferase in metabolism.  

 Alanine Aminotransferase

 Aspartate Aminotransferase

5. Describe the diagnostic importance of serum levels of Alanine  Aminotranferase and  

Aspartate Aminotransferase.  

 Liver diease

 High AST and ALT- markers of liver damage

 Increased cell death results in spilling of contents. When AST and ALT  are high in blood, it signals problem with liver

 Heart Attack (MI)

 High ASTin blood

 Troponin, LDH-1, CK-MB, Glycogen phosphorylase

 All better markers for heart attack

6. Briefly describe the metabolic roles of the non-protein N-containing  compound, glutathione.  

 Glutathione Roles

 Amino acid transport

 Leukotriene biosynthesis

 Protect cells from free radical and peroxide damage

 Eliminates toxins

 Cell signaling

7. What is Hemoglobin A1c and how is it related to the Maillard reaction?   When glucose binds to hemoglobin at lysine residues

 Good indicator of long term glucose control

 Once binds glucose, cannot be removed from hemoglobin. Bound until  cell dies

 Protein that’s measured in diabetics to monitor glucose control  Relation to maillard reaction

 Terminal amine group of hemoglobin binds aldehyde on glucose just  like methylglyoxal and formaldehyde with ammonia in the maillard rxn.

Carbohydrates:  

What is a “reducing sugar” and why is this property of some sugars  important in metabolism?  

∙ Reducing sugar has free aldehyde group.

∙ Reducing if can open up into chain form

∙ Monosaccharides are always reducing sugars

∙ Disaccharides sometimes are reducing sugars if aldehyde is not tied up in bond

∙ Reducing= lactose, galactose, glucose

∙ Diferent sugars have diferent reducing power

∙ Glucose can be a problem in a diabetes patient

∙ Hemoglobin A1C is a glycated protein

o Convenient diagnostic tool because good measure of long term  glucose control

o High hemoglobin A1C shows poor regulation of glucose ∙ Sucrose IS NOT a reducing sugar

o Aldehyde carbon of glucose and ketone carbon of fructose are  held up in a bond so neither sugar can open up

∙ Fructose is in open chain in highest amount

∙ Glucose is primary fuel in metabolism because a small amount exists  in open chain form

o 1.Glucose has very small percentage of aldehyde compared to  other aldose sugars

o 2. Stable ring that doesn’t open up

o Galactose is in open chain form 7x more than glucose

o 3. Doesn’t glycosylate as much as other sugars. If open chain,  more aldehyde is more reactive with amines (proteins)

o if used galactose as primary fuel, it would glycosylate and we’d  be dead fast

Describe the diferences (in terms of location, function, and regulation by  insulin) of the Glucose Transporters, GLUT1, GLUT2, GLUT4 and GLUT5.  ∙ GLUT 1

o Transports glucose across the apical side of epithelial cell in  conjunction with sodium

 Glucose can’t bind carrier until sodium binds

 Unidirectional import

o Not regulated by insulin

∙ Glut 2

o Transports glucose across the basolateral side into bloodstream o Transports fructose across basolateral side of cell

o Not regulated by insulin

∙ Glut 4

o Comes to edge of cell (when signaled by insulin) and removes  glucose from bloodstream to normalize blood glucose

o NOT IN LIVER

o Regulated by insulin (muscle, heart, adipose)

o Secretion of insulin by pancreas signals muscle and adiposites to  take up glucose by GLUT 4

o Signal transduction cascade signals GLUT 4 to come to edge of  cell and remove glucose from bloodstream

o Insulin binds muscle, phosphorylation signal in cell, GLUT 4  translocated to surface and facilitates glucose uptake, normal  blood glucose is achieved, insulin signal is reduced, GLUT 4 is  removed.

∙ Glut 5

o Transports fructose across apical side of cell

o Glucose enhances glut 5  

o Not regulated by insulin

Describe the diferences (in terms of function and regulation) between  hexokinase and  

glucokinase.  

∙ Glucokinase

o Converts glucose to glucose 6 phosphate in liver

o Low affinity for glucose

o High Km, lower affinity

o High Vmax

o Can metabolize more glucose at a higher rate

o Works over a large range of glucose concentrations- works better when glucose concentrations are really high and needs to be  metabolized

o Induced by insulin

∙ Hexokinase

o Not in liver, IN MUSCLE

o Converts glucose to glucose 6 phosphate in muscle

o Higher affinity for glucose

o Lower Km, higher affinity

o Lower Vmax

o Muscle grabs glucose even when glucose concentration isn’t that high- muscles need ATP to do work (ex. Heart)

o Works when very little glucose is present

o Gets maxed out really quick, so doesn’t work well when glucose  concentrations are high

o Not induced by insulin

Describe and cite examples of allosteric, covalent modification, and enzyme  induction regulation of carbohydrate metabolism.  

∙ Allosteric enzyme regulation

o Interaction with enzyme that changes affinity for substrate

o Activation/inhibition

o EXAMPLE INSERT HERE- statin drugs

o Fructose 6 phosphate-> fructose 1,6 BP

o cAMP is allosteric modulator of PKA

o active PFK2 turns on glycolysis

o when PFK 2 low (low insulin), favors gluconeogenesis

o Fructose 2,6 BP is positive allosteric modulator of PFK1

o Fructose 2,6 BP is produced by PFK 2

o PFK 2 is activate in dephosphorylated form

∙ Covalent modification

o Adding or removing phosphates via kinases and phosphatases o Ligand binds receptor and causes conformational change in G  protein. cAMP made which activates internal signal that regulates enzyme activity

o Phosphorylation of PFK2 or FBP 2 in hormonal regulation of  carbohydrate metabolism

∙ Enzyme induction

o Increase in protein synthesis to stimulate production of enzyme o Examples:  

Describe and compare the metabolic efects of insulin and glucagon on  carbohydrate metabolism.  

∙ Metabolic efects of insulin on carbohydrate metabolism.  o Increase glycogen synthesis in liver and muscle  

 Favors storage of energy.

o Increase GLUT 4 transporters in muscle and adipose tissue  Glucose brought into cell to make ATP or be stored as  

glycogen

o Inhibit glycogenolysis and gluconeogenesis

 Glycogenolysis = break glycogen down to glucose

 Gluconeogenesis = making glucose

o Inhibit hormone sensitive intracellular lipase (breaks down  triglycerides to free fatty acids so they can be used to make  energy)

o Induces lipoprotein lipase

 Lipoprotein taken from blood and stored in adipose to  

synthesize triglycerides and store them

o Stimulate amino acid uptake and protein synthesis

∙ Metabolic efects of glucagon- breaks down storage energy to incease  availability of glucose

o Stimulates glycogenolysis in liver (breaks down glycogen in liver  to get glucose) NOT IN MUSCLE

o Increases gluconeogenesis in liver (make glucose)

o Activates lipolysis

 Fatty acids are used to make ketones

o Increase amino acid uptake

o Gives carbon skeleton for gluconeogenesis

How do insulin and glucagon function to regulate glycolysis and  gluconeogenesis via fructose 2,6-bisphosphate.  

∙ When insulin is high

o Stimulates conversion of fructose 6 phosphate to fructose 1,6  bisphosphate by PFK 1 (irreversible step)

o Fructose -> Fructose 1,6 BP is rate limiting step (irreversible) o Bifunctional enzyme = can function in two diferent ways  depending on how it’s covalently modified  

 bifunctional enzyme is dephosphorylated , PFK 2 is active  and FBP-2 is inactive

 PFK 2 catalyzes the conversion of fructose 6 phosphate to  fructose 2,6BP

 Fructose 2,6 BP is a positive allosteric modulator of PFK 1  so glycolysis is STIMULATED

∙ When glucagon is high (hypoglycemia)

o cAMP production is stimulated by glucagon

o cAMP positively allosterically modulates protein kinase

o bifunctional enzyme is phosphorylated by the kinase

o PFK 2 is phosphorylated (inactive)

o FBP-2 is active

o Fructose 2,6 BP is not made, so levels are lower

o Less fructose 2,6 BP means fructose bisphosphatase 1 can  convert fructose 1,6 BP back to fructose 6 phosphate and  

increase gluconeogenesis

o Increase rate of gluconeogenesis  

Maillard Reaction and Advanced Glycation End-Products:  

Briefly describe the initial steps in the Maillard reaction (through Amadori  rearrangement).  

∙ Happens in food and in vivo

∙ Before color is formed (early steps), reaction can be reversed ∙ 1. Schif base

∙ 2. Intermediate: double bond switches place

∙ 3. Amadori rearrangement (irreversible) to get an amadori compound  (1 amino-1 deoxy-2 ketone).  

o Shifts where double bond is

o Once amadori step is formed, new amines can react to make new compounds

∙ melanoids= brown pigments that form at the end of maillard reaction

What are Advanced Glycation End-Products (AGE’s)?

∙ compounds formed in you and in food

∙ end products of maillard reaction (not pigments, but other compounds  formed after amadori compound)

∙ associated with aging and chronic disease (type 2 diabetes, CVD,  atherosclerosis)

∙ accumulate them over lifetime

Why are AGE’s of health concern?  

∙ Cause vascular damage

o Sugars bind proteins that result in less elasticity

o Normal turnover of blood vessels slows down

∙ Cause oxidative stress- more reactive oxygen species are produced  when AGE’s react with a cell

∙ Oxidize LDL’s which causes plaque formation and promotes  atherosclerosis

∙ Secrete pro-inflammatory cytokines

∙ Examples: CML(carboxy methyl lysine used to measure how much AGE  is in you), pentosidine, glucosepane= find in highest amount as result  of AGE production.

o Crosslinking of protein occurs which impairs protein function. ∙ Low AGE diet = low temp cooking like poaching or boiling ∙ High AGE diet = high temp cooking like frying

What are the major diferences between the AGE receptors, RAGE and AGE R1?  

∙ RAGE= makes problem worse

o When AGE binds receptor, stimulates changes that result in  accelerated inflammatory response and increase in reactive  oxygen species

o Results in pro-inflammatory gene activation

o Increases pro-inflammatory cytokines

 When AGE binds RAGE, NK-kB is activated and pro

inflammatory cytokines and produced (IL-Ioc)

 Pro-coagulant, vasoconstrict, enhanced adhesion

o Increases ROS (reactive oxygen species)

∙ AGE-R1= makes problem better

o Plays role in removal of advanced glycation end products o AGE’s endocytosed and degraded

o Enhances insulin receptor activity

o Suppresses ROS

High Fructose Corn Syrup:

Describe the basic diferences and similarities between the chemical  compositions of sucrose, HFCS, pure fructose, and pure glucose.  ∙ Sucrose

o Glucose and fructose

o HFCS and sucrose are basically the same

∙ HFCS

o 55% fructose

o 45% glucose

o no diferent than other caloric sweeteners

o doesn’t cause obesity or diabetes more than other sugars o causes small rise in uric acid

 not enough to cause diabetes

∙ pure fructose

o intake causes rise in uric acid

o doesn’t exist in normal nature

o studies where pure fructose were administered to look at HFCS  risks. Pure fructose causes lipogenesis, but HFCS does not

o pure fructose causes problems while sucrose does not

o GLUT 5 transports fructose across apical side and does not work  well when there is no glucose, so GI stress occurs

∙ pure glucose- don’t really need to know

What is the diference between the absorption and metabolism of fructose,  as compared to  

glucose?  

∙ Fructose

o Doesn’t end up in blood

o Processed in liver immediately

o Absorption of fructose results in less glucose output from the  liver which is why glucose goes down when fructose goes up o GLUT 5 transports fructose across the apical side of the cell (as  long as glucose is also present) FRUCTOSE WILL NOT BE  

ABSORBED IF NO GLUCOSE PRESENT

o GLUT 2 transports fructose across the basolateral side of the cell o Fruktokinase metabolizes fructose in liver

∙ Glucose

o GLUT 1 (sodium glucose transporter 1) transports glucose across  the apical side of the cell

o GLUT 1 needs to bind sodium before it can bind glucose  Affinity for glucose to bind increases after sodium binds to  transporter

 Unidirectional import

o GLUT 2 transports glucose across basolateral side of cell

What are the principle issues raised regarding the health efects of HFCS?  ∙ 1. Contains dangerous levels of reactive carbonyls (such as fructose) o As hemoglobin A1C (glycated hemoglobin)levels increase, heart  disease risk increases

o Hemoglobin A1C levels go down as fructose intake increases o Fructose doesn’t end up in the blood, it is processed in the liver  immediately

o Fructose absorption results in less glucose output from the liver  which is why glucose goes down when fructose goes up

∙ 2. Consumption can lead to fructose intolerance

o type 1 fructose intolerance: hereditary fructose intolerance  genetic deficiency in aldolase B which converts fructose 1  phosphate to glyceraldehyde and DHAP

 traps fructose 1 phosphate in the liver and can cause  

hepatic failure and death

o type 2 fructose intolerance: malabsorption of fructose from GI  tract

o GLUT 5 transports fructose across apical side as long as  glucose is present

o Can only occur if consume large amounts of pure fructose  which is not realistic with HFCS because it’s 50/50  

glucose/fructose

∙ 3.stimulates lipogenesis in liver (accumulation of fat in liver)  FRUCTOSE SKIPS PFK 1 STEP IN GLYCOLYSYS

o if PFK1 is bypassed, a lot of NADH is made, ATP increases, NADH  inhibits the krebs cycle and citrate builds up. Citrate positively  allosterically modulates acetyl coA carboxylase (the rate limiting  enzyme in fatty acid synthesis)

o overall idea: the more citrate builds up, the more fatty acids are  synthesized

o when ATP needs are met, you start to store energy in form of  fatty acids

o no significant diference in triglycerides in the blood between  people who consume glucose compared to those that consume  fructose (or sucrose vs. HFCS)

o HFCS has no efect on lipogenesis in obese or lean subjects o Lipogenesis is not stimulated by HFCS, fructose or sucrose o NO SIGNIFICANT DIFFERENCE BETWEEN ANY OF THE TISSUES ∙ 4. Increases uric acid production

o decreases nitric oxide availability needed for normal vascular  function

o nitric oxide stimulates vasodilation

o uric acid inhibits nitric oxides ability to promote vasodilation

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