Alcohol Metabolism/Integration of Pathways
Alcohol Metabolism/Integration of Pathways HUN3224
Popular in Intermediary Metabolism
Popular in Nutrition and Food Sciences
This 16 page Bundle was uploaded by Channelle Brown on Saturday April 23, 2016. The Bundle belongs to HUN3224 at Florida State University taught by Dr. Farrell in Spring 2016. Since its upload, it has received 24 views. For similar materials see Intermediary Metabolism in Nutrition and Food Sciences at Florida State University.
Reviews for Alcohol Metabolism/Integration of Pathways
Report this Material
What is Karma?
Karma is the currency of StudySoup.
You can buy or earn more Karma at anytime and redeem it for class notes, study guides, flashcards, and more!
Date Created: 04/23/16
Alcohol Metabolism Commonly associated with vitamin/mineral deficiency Not a macronutrient because it is a toxin Still has calories Dietary guidelines o If you choose to drink, guidelines (moderate): Equal to or less than 2 drinks/day – men Equal to or less than 1 drink/day – women o 1 drink provides ½ oz. of ethanol 12 oz. beer 10 oz. wine cooler 1.5 oz. liquor (80 proof) 1 oz. liquor (100 proof) 5 oz. wine o Flavored alcohol – more flavoring/calories, less alcohol o Ethanol: combo of carbs and alcohol Carbs are fermentedyeast gives off alcohol o Alcohol = 7kcal/g TopHat: Per gram, does alcohol provide more calories than fat? o Answer: fewer than fat (9kcal/g), more than carbs (4kcal/g) How many calories of EtOH in a 12 oz. beer is 5% ABV (alcohol by volume)? o 0.8 g/mL x ABV% x volume of beverage (mL) = g of alcohol o E.g. – 0.8 g/mL x 0.05 x (12 oz. x 30 mL) = 14.4 g EtOH o 1 oz.=30 mL o Budweiser 5%, 145 calories o Budlight 4.2%, 110 calories (lower caloriesless ethanol) Alcohol Metabolism o 3 systems Alcohol dehydrogenase (ADH) Located in gastric mucosal cells in : o Gut (stomach) o Hepatocytes (liver) ADH levels: o Men > women (why women die of alcoholism more than men) o Asian, natives, etc. < Europeans (why Asians get ‘Asian flush’ when drinking too much; not an allergy, just an intolerance) o Without ADH, it’s harder to break down alcohol Function: o Converts an –OH into an aldehyde o Requires NAD Men/Europeans: can consume more alcohol since they break them down faster o Reactions: Ethanolacetaldehyde (still toxic) Increases inflammation in GI tract those with IBS, problems with tract, etc. should avoid alcohol Retinolretinal (vitamin A) Can affect vision More retinol used to metabolize alcohol so not as much goes to vision/eyes o *amount of enzymes produced varies o When we don’t have enough NAD to break down all EtOH(in blood) intoxication TopHat: Where does alcohol metabolism begin? o Answer: stomach Acetalydehyde Dehydrogenase Located in liver Function o Acetaldehydeacetate o Requires NAD Makes energy o Goes into Krebs cycle Problems: o Saturation of enzymesgoes to brain (we use all ADH and cannot break acetaldehyde downgoes to bloodintoxication/inflammation) o Depletion of NAD= decreased B vitamins Deficiency found commonly in alcoholism Microsomal ethanol oxidizing system (MEOS) Location: smooth endoplasmic reticulum in hepatocytes (liver) o This is why you cannot get rid of intoxication at whatever time you want; liver metabolism is timed SERworks like ETC o Utilizes riboflavin (FAD and FADH) and niacin (NADPH) o Cytochrome p450 (protein) End products: o Water, NADP o Acetaldehyde Inducible o We can change it if we drink more alcohol o Increased SER funtioning o Increased P450 Metabolizes xenobiotics o Why we don’t take medications and alcohol together Medications can change the metabolism of other drugs DrugsMEOS pathway Especially prescription painkillers It can double the effects and make it work faster/worse MEOS pathway is smaller for people who don’t drink as often Large MEOS when people consume a lot regularly (alcohol is metabolized faster) o MEOS=contributes a lot to tolerance o This pathway is very sensitive o “spillover pathway” o Dependent on ADH o Large personlarge blood volumethey can consume more (EtOH is more spread out throughout body) Amount of fat free mass and fat mass doesn’t seems to make a difference since this pathway deals with hepatocytes in the liver o In alcoholics and those who regularly drink, MEOS will be induced before ADH is completely saturated; the body knows more drinks are coming Catalase Utilizes hydrogen peroxide <2% EtOH oxidation Acetate About 20-30% stays in the liver o Acetateacetyl CoA o De novo fatty acid synthesis o Fatty acids: stay in liver, enter blood via VLDL About 70-80% enters blood stream o Signals decreased fatty acids from adipose o Fatty acids that are released travel to liver Enters muscle tissue o Acetateacetyl CoA o Oxidized to energy o Other Metabolic Changes in Response to Ethanol Body slows other metabolic processes to metabolize alcohol Gluconeogenesis decreases (hypoglycemia) Protein synthesis decreases Krebs cycle slowsfatty acid synthesis Fatty acid synthesis increases Ketone formation increases NADH: NAD ratio increases Running out of NADcannot metabolize alcohol Why we make lactate from pyruvate to make more There is a lot of disregulation when we consume alcohol Organ specific GI tract o Stomach increases HCl secretions o Acetaldehydetoxic (especially to mucosal cells) Decreases intestinal absorption of almost all vitamins, especially B vitamins o Increases in iron absorption (in liver)where “stop” mechanism is Damaged liverunregulated amount of iron comes intoxicity o Risks of GI tract cancers increases Kidneys o Increased excretion of: Mg, K, Ca, Zn (electrolytes) o Decreases ADH production More fluid loss because of increased urine excretiondiuresis Brain o Decreased oxygen o Can shut down if too loss EtOH, loss of consciousness Protective mechanism so that the body can’t consume anymore Passing out – due to how the body metabolizes Liver o Fatty liver – fat builds up After a day of drinking, you can see fat on the liver It will eventually go away Can be seen with alcoholics or nonalcoholics o Hepatic disease (cirrhosis) Scar tissue builds up on liver o Lactic acidosis o Remember: the liver is the main storage site for vitamins and converts vitamins to metabolically active forms o Vitamin and Mineral Changes with EtOH Fat soluble Vitamin E o Antioxidant – protects cell and organelle membranes o Depleted with chronic EtOH (cell damage) vit. E is used Vitamin A o EtOH consumption=decreased levels of vitamin A o Retinolretinal via retinol dehydrogenase The retinol dehydrogenase is “stolen” by EtOH Low vitamin A, less retinol o Supplementation may lead to toxicity due to decreased liver function (too much of a good thing can be bad) Water soluble – B vitamins When drinking lots of alcohol, the body can’t use B vitamins so they go through the urine and leave the body B1 = Wernicke-Korsakoff syndrome o Psychosis o Can be seen in those even after the quit drinking alcohol o ‘leftover alcoholism’ o Thymine deficiency = effects of drunkenness, ataxia, shifting eyes, short-term memory loss Folate (B9) o Responsible for cell division/differentiation Niacin and Riboflavin Biotin (B7) and Pantothenic Acid (B5) o Decreased intestinal transporter Vitamin C Antioxidant, carnitine Why? o Intestinal transport? Cellular transport? Decreased conversion of vitamin to active form (liver)? Increased utilization of vitamin? Iron Increases iron absorption Liver usually puts a stop on iron absorption (regulates it), but if the liver is damaged, iron comes in unregulatedtoxicity o Toxicity can be seen in alcoholics who continue to eat heavily o Can also lead to hemochromatosis (iron overload) o Hangover Dehydration Increased fluid output with more EtOH consumption Low blood sugar Body metabolizesglucose into liver Treatment/prevention? CHO containing food? B. vitamin before drinking? o Not really effective unless you already have a deficiency in B vitamins o If you don’t have a deficiency, you will just urinate them out OTC analgesics? o Can help the symptoms (e.g. – headache, sore muscles from increased lactate, etc.) o They are metabolized through the liver so just be careful about the amount taken Antioxidants? o Won’t really hurt TopHat: Why might alcoholics have iron toxicity? Answer: Decline in liver function results in increased iron absorption. TopHat: Chronic alcoholics have what kind of malnutrition? Answer: Kwashiorkor – with alcohol, there are plenty of calories but there’s low protein and distended fatty livers Integration of Cycles (*the Energy Expenditure lecture part of the slides is already all up on Blackboard) Krebs cycle o Amphibolic pathway o Central to metabolism o Involved in both catabolism and biosynthesis of carbs, fats, and protein Acetyl CoA o Pyruvate dehydrogenase reaction is not reversible Reaction: pyruvateacetyl CoA o Must be used for energy, fatty acid synthesis, cholesterol synthesis, ketogenesis Fed vs. Fasting o Occurs in shifts o Not clear cut o Fed Primary hormone: insulin o Fasting In stages and depends on the individual Glucose-dependent tissues – erythrocytes, brain/central nervous system We have to eat in order to get glucose; it is limited Initially: Glucose levels drop (below 60=BAD) Glycogen stores are broken down o GlycogenG6P (only in liver) Circulating amino acids are used for gluconeogenesis We have lots of fat stored o Fatty acid are released in higher quantities Few days: Glucogenic amino acidskeep glucose levels up Glycerol can also be turned into glucose Fatty acids in other parts of body, metabolized into ketones Early weeks: Body conserves energy Lowers body temperature, blood pressure, and kidney function Minimal gluconeogenesis, spares body protein About 10 daysbrain/CNS have to adapt to ketones o Ketone production increases o Some parts of brain only uses glucose Minimal Krebs cycle as well TopHat: What is happening to BMR at this point? Answer: decreases but it depends (no right answer) o Depends on person and how long they’ve been fasting o Too efficient: ketosis o But body is trying to offset ketosis: body functions decline, making our body survive through starvation periods Several Weeks: Immune system declines Fat stores are nearly depleted Body begins to use lean body mass for energyPEM (protein malnutrition) Near death (about 2 months) Organs broken down for energyorgan failure Even if that individual survives, there will be some permanent damage to organs Women can survive longer than men since they have a higher percentage of essential fat It can depends on activity level Refeeding Syndrome (AKA hypophosphatemia=low phosphate levels) o At-risk Severely malnourished Anorexics Morbidly obese after massive weight loss The body still thinks it’s starving o What is it? Abnormal metabolism resulting from an abrupt shift from fat to carbs as a substrate when a person is aggressively fed after a period of starvation; can be deadly (research: concentration camp survivors) o Symptoms/complications Hypotension Edema Respiratory failure (due to the body straining) Myocardial dysfunction (due to body straining) Muscle weakness Tachycardia Dizziness o Why? Starvation Body uses fat for energy Glucagon=main hormone Begin to aggressively refeed Increased insulin to cover CHO influx Decreased glucagon o Decreased gluconeogenesis, fatty acid mobilization Increased insulin levels induce glucose uptake into cells At the same time: Phosphorous in blood – driven into cells/tissues Decreased phosphorous in bloodstreammuscle weakness K, Mg, pulled into cells o Decreased serum electrolytes body begins to retain fluid in extracellular spaceedema o Organ Specific Heart: increased cardiac workload Gut: atrophy with starvation o Treatment Initially: restrict CHO and gradually increase Increase protein to restore lean body mass This won’t cause a big shift to insulin like carbs do Maintain fluid balance (clinically) monitor lab electrolyte values o K, Mg, Na, Phosphorous Metabolic Syndrome o Cluster of symptoms (3 out of 5) Elevated waist circumference Equal to or > 40 in – men Equal to or > 35 in – women Elevated triglycerides Equal to or > 150 mg/dL Low HDL levels <40 mg/dL – men <50 mg/dL – women High blood pressure SBP: equal to or > 130 mmHg DBP: equal to or > 85 mmHg Increased fasting glucose Equal to or > 100 mg/dL o Values vary in different areas of the world. The U.S. has stricter values than others. o TopHat: Diabetes is a diagnostic criteria for metabolic syndrome. Answer: False. It is not linked to this syndrome. o Insulin resistance Hyperinsulinemia More insulin released from pancreas to regulate blood glucose Increased insulin and glucose levels (neither are being used) Tissues Muscle (GLUT4 dependent) – insulin no longer stimulates glucose uptake Adipose tissue – unregulated free fatty acid release Liver (not GLUT4 dependent) – retains insulin sensitivity; picks up all glucose o Insulin stimulates triglyceride synthesisfat (adipose tissue) o Increased VLDL and serum triglycerides stay in liverfatty livernonalcoholic fatty liver disease Kidney – retains insulin sensitivity, tries to take care of glucose o Increases sodium retentionhypertension o Treatment Medications for symptoms: polypharmacy (multiple meds can cause even more problems because of side effects, etc.) Weight loss Diet – low fat is not beneficial if they are high simple carbs Exercise o Physical Traits/Symptoms Acanathosis nigricians – darkening around the neck/other body folds and creases Lipodystrophy and more fat around the neck area Excess adipose tissue that is visceral fatmore dangerous since it is putting pressure on organs o TopHat: How does exercise help with insulin resistance? Answer: helps move glucose into GLUT4 mediated cells Diets o Low fat High CHO and low protein Low protein – cannot maintain lean body mass About 10% fat (normal intake – about 30%) Examples: Dean Ornish (vegetarian), Pritikin (lean meat) Advantages: decreased saturated fat Metabolism: increased CHOincreased insulinstorage o Depending on calories consumed, you can still see weight gain o Low fat foods use sugar to replace the fat o Low CHO diets Tend to be high in protein and fat Some as low as 5% CHO (tricks body into ketosis) Examples: Atkin’s, Southbeach, Sugar Busters Advantages: protein sparing (keep LBM), no calorie counting since ketosis is less efficientweight loss Metabolism: Initially: increased glycogenolysis Over time: lipolysis, beta-oxidation, ketogensis o Paleo diets Different kinds for men, women, and active people High in protein and veggies, low in fruits and fat/oils o All of these diets could have been somewhat healthy if marketing/food companies didn’t catch on o Eat real, whole foods and have a balanced diet *We did not go over muscle/exercise for the exam. Final Exam Info: o 75-80 questions o 27% of grade o Comprehensive from each section o Do not need a calculator o She likes integration of cycles/combined questions Alcohol Metabolism/Integration of Pathways – Diagrams/Charts
Are you sure you want to buy this material for
You're already Subscribed!
Looks like you've already subscribed to StudySoup, you won't need to purchase another subscription to get this material. To access this material simply click 'View Full Document'