Biochemistry Exam 3 Study Guide
Chapter 12: Membrane Structure and Function
Membranes are sheetlike structures only two molecules thick that consist mainly of lipids and proteins along with carbohydrates. Membrane lipids are amphiphilic and form spontaneously through noncovalent interactions. Proteins mediate specific functions of membranes as pumps, channels, receptors and enzymes. Membranes are asymmetric with different compositions on the inside and outside, are fluid structures and their components diffuse rapidly within each side of the membrane. Most cell membranes are electrically polarized for transport, energy conversion and excitability. Na+ K+ ATPase is an ATPdriven pump where the Na+ gradient controls cell volume, electric excitation of neurons and muscle cells and active transport of sugars and amino acids. Secondary transporters use concentration gradients in one chemical to establish gradients of another. An example of an ion channel is the potassium ion channel which transports K+ across the membrane.
Chapter 14: Digestion
Metabolism is the chemical pathways that allows a cell to extract energy to use for biosynthetic purposes. Catabolism produces energy and anabolism requires energy. Zymogens are inactive substances that are converted into enzymes when activated by another enzyme. Different enzymes are active depending on the position in the digestive system whether in the mouth, stomach, or intestine. Polypeptide fragments from the stomach stimulate release of CCK to which the pancreas responds by releasing digestive enzymes into the intestine. Most lipids are ingested in the form of triacylglycerols and must be degraded to fatty acids for absorption. After transport into the SER, the triacylglycerols associate with specific proteins and a small amount of phospholipid and cholesterol to form lipoprotein transport particles chylomicrons.
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Chapter 15: Metabolism
Free energy is sued for performance of mechanical work in muscle contraction and cellular movements, active transport of molecules and ions, and synthesis of macromolecules and other biomolecules from simple precursors. The regulated, irreversible reactions in metabolic pathways are almost always distinct from each other. ATP in what provides free energy in biochemistry where energy is stored in the phosphoanhydride bonds. ATP stores energy because it has a 4 charge, ADP has greater resonance than ATP, splitting ATP causes increase in entropy, and ADP has a more stable hydration compared to ATP. Activated carriers include ATP/ADP, NAD+/NADH, FAD/FADH2, NADP+/NADPH and acetyl CoA. Metabolism is regulated by controlling the amount of enzymes, controlling substrate accessibility and regulating catalytic activity. Energy charge and phosphorylation are used to determine the energy status of the cell. If you want to learn more check out What is the outermost region of the sun’s atmosphere?
Chapter 16: Glycolysis
Glycolysis is an energyconversion pathway that breaks down glucose to produce ATP, pyruvate and NADH. In the preparatory phase, glucose is converted to glucose6phosphate to fructuose6phosphate to fructose1,6bisphosphate to 2 glyceraldehyde 3phosphates. During this phase, 2 ATPs are invested. In the payoff phase, glyceraldehyde 3 phosphate is converted into 1,3bisphosphoglycerate to 3phosphoglycerate to 2phosphoglycerate to phosphoenolpyruvate to pyruvate. This all happens twice because there were 2 glyceraldehydes 3phosphates. This phase produces 4 total ATP molecules and 2 NADH, making the total net gain of glycolysis 2 ATP and 2 NADH. Each step in glycolysis is regulated by an enzyme. Kinase is an enzyme that catalyzes the transfer of a phosphoryl group from ATP to an acceptor. Glycolysis is regulated at irreversible reactions by three allosteric enzymes: PFK, hexokinase and pyruvate kinase. These enzymes can be up or downregulated in response to different stimuli.
Chapter 17: Gluconeogenesis
Gluconeogenesis is essentially the reverse reaction of glycolysis where glycolysis converted glucose into pyruvate and gluconeogenesis converts pyruvate into glucose. Pathways for gluconeogenesis share steps 2 and 49 with glycolysis but not the exact reversal process. The crucial steps 1, 3 and 10 are catalyzed by different enzymes. The first step pyruvate is converted
into oxaloacetate by pyruvate carboxylase before being converted into PEP by PEP carboxykinase. Fructose 1,6bisphosphate is converted into fructose 6phosphate by fructose 1,6 bisphosphatase. Glucose 6phosphate is converted to glucose by glucose 6phosphatase. 4 ATP and 2 GTP are put into gluconeogenesis to produce glucose. Gluconeogenesis and glycolysis are reciprocally regulated. The liver is the main site of gluconeogenesis and one function of the liver is to keep bloodglucose levels stable. The hormones insulin and glucagon are used to signal bloodglucose levels. We also discuss several other topics like Define conformity.
Chapter 12: Membrane Structure and Function
1. What are membranes?
a. Membranes are selective barriers that only allow certain compounds to pass b. They define the inside from the outside of cells themselves and intracellular organelles
2. What are basic features of membranes?
a. Sheetlike structure only two molecules thick Don't forget about the age old question of What are some benefits of orienting employees?
b. Consist mainly of lipids and proteins along with carbohydrates
c. Membrane lipids are amphiphilic and form spontaneously through noncovalent interactions
d. Proteins mediate specific functions of membranes as pumps, channels, receptors, and enzymes
e. Membranes are asymmetric with different compositions on the inside and outside f. Membranes are fluid structures and their components diffuse rapidly within each side of the membrane
g. Most cell membranes are electrically polarized for transport, energy conversion and excitability
3. How do membranes form?
a. Membranes selfassemble as a result of the inherent structure of their constituent lipid molecules
b. Phospholipid and glycolipid components are amphiphilic having hydrophobic and hydrophilic components
4. What is the hydrophobic effect?
a. The hydrophobic effect causes the hydrophobic tails to point inwards, away from the water, while hydrophobic regions interface with water
b. Van der Waals forces between the hydrocarbons inside reinforce the membrane c. Polar head groups interact through electrostatic and hydrogen bonds with the surrounding water
5. How permeable are membranes? Don't forget about the age old question of Who is mr. doughty?
a. Membranes have a very low permeability for ions (Na+, K+, Cl) and most polar molecules
b. The permeability of small molecules is correlated with their relative solubilities in water and nonpolar solvents
6. What state do membranes exist in?
a. Membranes can exist in an ordered, rigid state or in a relatively disordered, fluid state as determined by the melting temperature Tm
b. Tm is dependent on the length of fatty acid chains and their degree of saturation c. Lateral diffusion, within one side of a membrane, is rapid
d. Transverse diffusion, or flipflopping is very rare
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a. Cholesterol within the lipid bilayer disrupts the ordering of the hydrophobic tails, increasing membrane fluidity
b. Hydroxyl group of cholesterol forms a hydrogen bond with the phospholipid head group
8. What are lipid rafts?
a. Dynamic 10200 nm complexes formed by cholesterol, phospholipids and proteins in the cell membrane
b. Concentrate proteins required for signaltransduction pathways and facilitate interactions between extracellular matrix and the cytoskeleton
9. What do proteins in membranes do?
a. Proteins are responsible for most of the dynamic processes carried out by membranes
b. Membranes performing different functions contain different kinds and amounts of proteins
10. What are integral membrane proteins?
a. Embedded in the hydrocarbon chains of membrane lipids
11. What are peripheral membrane proteins?
a. Bounds to head groups of lipids or exposed portions of integral proteins through electrostatic or H bonds
12. What types of proteins are in membranes?
a. Membranespanning alpha helices are the most common structural motif in integral membrane proteins
b. Nonpolar B sheets can also be used to interface with membrane interior 13. What are bacteriorhodopsin?
a. Use light energy to pump protons from inside to outside
14. What are bacterial porin?
a. Hollow cylinder that forms a channel for transport across membrane 15. What are transporter proteins?
a. Some molecules can pass through membranes via simple diffusion b. Transporter proteins enable specific, impermeable molecules to be transported across the membrane
16. What is facilitated diffusion (passive transport)?
a. Energy driving movement arises from the ion gradient itself
17. What is active transport?
a. Employ an energy source to move a molecule up a concentration gradient 18. How does the ATPdriven pump work?
a. Animal cells contain a high concentration of K+ and a low concentration of Na+ relative to the extracellular fluid
19. What are the functions of Na+ gradient?
a. Controls cell volume (through osmolarity)
b. Electric excitation of neurons and muscle cells
c. Active transport of sugars and amino acids
20. What are different types of Ptype ATPases?
c. P4ATPase (lipid flippases)
21. What are secondary transporters (cotransporters)?
a. Use concentration gradients in one chemical to establish gradients of another 22. What is a sodiumglucose linked transporter (SGLT)?
a. A symporter for glucose powered by simultaneous entry of Na+
b. Generates a 66fold concentration gradient of glucose in the cell from ~10fold of Na+
23. What are ion channels?
a. Ion channels enable specific transport of ions across the membrane b. Can transport with extraordinary speed, up to 1000fold faster than active transporters and close to freely diffusing species
c. Can respond to chemical and physical changes in the environment (voltagegated and ligandgated channels)
d. Nerve impulses, or action potentials, make use of ion channels for rapid transport of Na+ and K+
24. What is a potassium ion channel?
a. An example of an ion channel, which specifically transports K+ across the membrane
b. A large diameter region on the cytoplasmic side accepts K+ and a narrower diameter portion selections K+ ions specifically
25. What is a selectivity filter?
a. A precise arrangement of carbonyl groups in this filter region enable water interactions around K+ to be replaced with carbonyl interactions
26. Why don’t Na+ ions flow through the potassium ion channel very frequently? a. Potassium ion channels are 100fold more permeable to K+ then to Na+ b. Sodium ions are too small to react with the selectivity filter
c. Carbonyl groups are not positioned well enough to enable energetically replacement of water solvation shell when Na+ is in the channel
d. Fast transport of K+ due to four energetically equivalent binding sites in selectivity filter and electrostatic repulsion
Chapter 14: Digestion
1. What is metabolism?
a. The highly integrated network of chemical pathways that enables a cell to extract energy from the environment and use this energy for biosynthetic purposes 2. What are two categories of metabolism?
a. Catabolism: the set of metabolic reactions that transform fuels into cellular energy
b. Anabolism: the set of metabolic reactions that require energy to synthesize molecules from simpler precursors
3. What are requirements for digestion?
a. The food we consume must be broken down into simpler precursors that the body can use for its metabolism
b. Different enzymatic processes are employed for digesting the four major types of biomolecules
c. All the digestive enzymes are hydrolyases
4. How do we control where digestion occurs?
a. Through the use of zymogens
5. What are zymogens?
a. Apart from alphaamylase, all digestive enzymes are secreted as inactive forms known as zymogens or proenzymes
b. Zymogens are activated by subsequent proteolytic cleavage
6. What is the zymogen in the stomach?
a. Pepsin(ogen) cleaves itself for activation
7. What are the zymogens in the pancreas?
a. Chymotrypsinogen, trypsinogen, procarboxypeptidase and proelastase b. Enteropeptidase activates trypsin(ogen); trypsin then activates remaining pancreatic zymogens
8. What are the stages of digestion?
i. Saliva contains ions (Na+, K+, Cl, HCO3), mucoproteins, alphaamylase, and salivary lipase to assist with swallowing and begin digestion
i. Low pH levels in the stomach (pH 12) denature proteins and enable proteolytic breakdown by pepsin
ii. pH levels established by K+/H+ ATPase
i. the intestine neutralizes stomach acids by secreting sodium bicarbonate in response to the hormone secretin
ii. a series of enzymes continues breakdown of proteins and begins the main process of breaking down lipids and carbohydrates
9. How does digestion in the intestine work?
a. Polypeptide fragments from stomach stimulate release of the hormone cholecystokinin (CCK)
b. The pancreas responds to CCK by releasing digestive enzymes into the intestine c. Oligopeptides (smaller polypeptides) are further digested by peptidases on the surface of intestinal cells and transported into the cells
10. What is glycogen?
a. A polysaccharide that is the most abundant homopolymer in animal’s cells and is the storage form of glucose
b. It features two types of glycosidic bonds:
i. Alpha1,4glycosidic bonds for linear regions
ii. Alpha1,6glycosidic bonds for branching every ~10 units
11. What is amylopectin?
a. Branched starch consisting of glucose with alpha1,4glycosidic linkages and branching alpha1,6glycosidic linkages every ~30 units
12. What is amylose?
a. Unbranched starch consisting of glucose in alpha1,4glycosidic linkages 13. What is the primary source of dietary carbohydrates?
b. Alphaamylase breaks down alpha1,4 bonds of starch but not the alpha1,6 bonds 14. What are disaccharides?
a. Formed by Oglycosidic bonds between two monosaccharides
b. Glycosidic bonds can be named according to the anomer and number of the carbon in the other sugar
15. How are monosaccharides imported and exported from cells?
a. Using transporters
16. How are lipids digested?
i. Lipids are converted into an emulsion via the grinding and mixing of the stomach
b. Bile salts
i. Amphiphilic cholesterol relatives released from the Gall bladder in response to CCK that make triacylglycerols more readily digested
i. Lipases released by the pancreas as zymogens degrade triacylglycerols into fatty acids and monoacylglycerol
17. What happens to the free fatty acids?
a. Free fatty acids and monoacylglycerol are carried in micelles to the plasma membrane of the intestinal epithelial cells for absorption
b. Fattyacidbinding proteins (FABP) bring lipid products into the cell
c. Fattyacidtransport proteins (FATP) transport them to the SER where they are further processed
d. Chylomicrons consisting of triacylglycerols enclosed within a
phospholipid/cholesterol/protein membrane for transport in the blood to adipose and muscle cells
Chapter 15: Metabolism
1. What are the three main purposes of free energy input?
a. Performance of mechanical work in muscle contraction and cellular movements b. Active transport of molecules and ions
c. Synthesis of macromolecules and other biomolecules from simple precursors 2. How do cells obtain energy from the environment?
a. Phototrophs: trap the sun’s energy in chemical form
b. Chemotrophs: oxidation of carbon fuels
3. What are principles of energy flow in life?
a. Fuels are degraded and large molecules are constructed step by step in a series of linked reactions called metabolic pathways
b. ATP is an energy currency common to all life forms. It links energyreleasing pathways with energyrequiring pathways
c. The oxidation of carbon fuels powers the formation of ATP
d. A limited number of types of reactions and particular intermediates are common to many pathways
e. Metabolic pathways are highly regulated to allow the efficient use of fuels and to coordinate biosynthetic processes
4. What is a metabolic pathway?
a. Process or a biomolecule from a starting point to an end point without the generation of wasteful or harmful side products
5. What are the two classes of metabolic pathways?
a. Catabolic reactions (catabolism)
i. Fuel CO2 + H2O + useful energy
b. Anabolic reactions (anabolism)
i. Useful energy + simple precursors complex molecules
6. How do you make a reaction favorable?
a. Not all reactions are thermodynamically favorable
b. An unfavorable reaction can be coupled to a favorable reaction
7. What is ATP?
a. ATP is the free energy provider of biochemistry
b. ATPADP cycle is the fundamental mode of energy exchange in biological systems
c. Considerable energy is stored within ATPs phosphoanhydride bonds 8. Why does ATP hold so much energy?
a. Electrostatic repulsion
i. At pH 7, ATP has 4 charge
ii. This is a considerable amount of repulsion in a confined space
b. Resonance stabilization
i. The products of ATP hydrolysis have greater resonance stabilization than ATP itself
c. Increase in entropy
i. Entropy increases as the number of molecules increases
ii. Hydrolysis of ATP yields one more molecule and thus increases entropy d. Stabilization due to hydration
i. Water bonds to ADP and Pi more effectively than to ATP alone
ii. This effect makes ATP hydrolysis more thermodynamically favorable 9. What is phosphoryltransfer potential?
a. A lot of compounds actually release more energy than ATP when their phosphoanhydride bonds are hydrolyzed
b. Standard free energy of hydrolysis: amount of energy released when a phosphorylated compound transfers its phosphoryl group to water under standard conditions
c. A molecule with a more negative standard free energy of hydrolysis can donate its phosphoryl group to one with a less negative value
10. Why does ATP have an intermediate phosphoryltransfer potential? a. So that it can donate and receive phosphoryl groups
11. Why are there phosphates on ATP?
a. Phosphate and its esters are thermodynamically unstable and kinetically stable 12. Why is kinetic stability a good thing?
a. Can be manipulated via enzymes
b. Negative charge makes them resistant to hydrolysis
c. Can be used for regulation
13. How does ATP consumption and production work?
a. A resting human uses about 88 lbs. of ATP per day
b. There is about 100 g of ATP in the human body at a given time. Each molecule is consumed within a minute of its formation
c. ATP must be continually produced to keep up with energy needs
d. Oxidation of carbon fuels provides the energy for ATP generation
14. What is the oxidation of carbon fuels?
a. Carbon fuels are oxidized to generate the final product CO2
15. What are oxidationreduction reactions?
a. Coupled reactions in which a molecule loses electrons and another molecule gains electrons
b. Carbon fuels that are more reduced will release more energy when they are oxidized
16. What are the three main functions of activated carriers?
a. Electron carriers for fuel oxidation
i. NAD+/NADH, FAD/FADH2
b. Electron carriers for biosynthesis
c. Carbon carrying
i. Acetyl CoA
17. What are electron carriers for fuel oxidation?
a. These carriers accept electrons from fuel molecules
b. The electrons are then transferred to O2
c. O2 is a more stable state for the electrons compared to the activated form of the electron carriers
d. Most biosyntheses have reactants that are more oxidized than products e. High potential electrons are also used for anabolic reactions
18. What are common properties of carriers?
a. Generally derived from vitamins and nucleotides
b. The activated forms are thermodynamically unstable and kinetically stable c. NADH, NADPH, and FADH2 react very slowly with O2
d. ATP and acetyl CoA require hours or days to be hydrolyzed
19. How is metabolism regulated?
a. Homeostasis, a stable biochemical environment, requires tight control of metabolism
b. Need to maintain balance between energy usage and chemical inputs c. Flexibility is required because the environment of the cells is constantly changing 20. What are the three general ways in which metabolism is regulated? a. Controlling the amount of enzyme
b. Controlling substrate accessibility
c. Regulating catalytic activity
21. How are amounts of enzymes controlled?
i. The cell can adjust the rate of transcription to produce the correct amount of enzyme for the pathway
22. How is substrate accessibility controlled?
a. Compartmentalization: eukaryotes employ organelles to control exactly where substrates are present inside the cell
i. Fatty acid synthesis: cytoplasm
ii. Fatty acid oxidation: mitochondria
b. Regulating substrate import
i. Insulin promotes glucose entry
ii. Permease promotes lactose entry in E. coli
23. How is catalytic activity regulated?
a. Feedback inhibition: the first step in many biosynthetic pathways is allosterically inhibited by the ultimate product of the pathway
b. Reversible covalent modification can be used to rapidly activate and deactivate catalytic activity
c. Hormones coordinate metabolic relations between different tissues
Chapter 16: Glycolysis (Part 1)
1. What is glycolysis?
a. Glycolysis is an energyconversion pathway that breaks down glucose to produce ATP, pyruvate, and NADH
b. Glucose is the most prominent monosaccharide fuel:
i. Potential for prebiotic synthesis
ii. The most stable hexose
iii. Low tendency to glycosylate proteins
c. Glycolysis is an ancient metabolic pathway common to nearly all eukaryotes and prokaryotes
2. What are the two stages of glycolysis?
a. Stage 1: preparatory phase
b. Stage 2: payoff phase (ATP production)
3. What is the net reaction of glycolysis?
a. 6carbon glucose is converted to two molecules of 3carbon pyruvate
b. Reactions are used to generate compounds with high phosphoryltransfer potential 4. What are the steps of stage 1?
a. Add phosphate #1
b. Convert to fructose (ketose)
c. Add phosphate #2
d. Evenly divide up carbons
e. Produce 2x glyceraldehyde 3phosphates
5. What are the steps of stage 2?
a. Create high energy phosphate using Pi, NAD+
b. Extract phosphate to make ATP
c. Mutate phosphate to middle carbon
d. Convert to enol form
e. Extract final phosphate to make ATP
6. What is the net reaction?
a. Glucose + 2 Pi + 2 ADP + 2 NAD+ 2 pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O
7. What is kinase?
a. An enzyme that catalyzes the transfer of a phosphoryl group from ATP to an acceptor
8. What does hexokinase do?
a. Transfers phosphoryl group from ATP to a variety of hexoses
b. This reaction is irreversible is most organisms
9. What purposes does phosphorylation of glucose serve?
a. Keeps glucose 6phosphate from leaving cell (no longer a substrate for transporters)
b. Addition of phosphate group is essential to downstream glycolytic reactions 10. What does phosphoglucose isomerase do?
a. Converts an aldose into a ketose
b. Glucose 6phosphate and fructose 6phosphate are isomers of one another 11. What does phosphofructokinase (PFK) do?
a. Acts on the phosphofructose to add the second phosphate group
b. This reaction is irreversible under cellular conditions
c. PFK is a key regulatory enzyme for glycolysis
12. What does aldose do?
a. It does a reversible reaction
b. Cleaves 6C fructose 1,6bisphosphate into 2x 3C molecules: dihydroxyacetone (DHAP) and glyceraldehyde 3phosphate
13. What does triose phosphate isomerase do?
a. Triose phosphate isomerase (TPI or TIM) catalyzes the reversible conversion between DHAP and GAP
b. At equilibrium, 96% of the triose phosphate is in the DHAP form c. Consumption of GAP in glycolysis drives production of more GAP 14. What are the details of stage 1 of glycolysis?
ii. 2 ATP
i. 2 GAP
ii. 2 H+
iii. 2 ADP
c. Irreversible steps
i. Hexokinase and phosphofructokinase (PFK) reactions
d. Reaction steps
i. Phosphate, swap, phosphate, cut, swap
15. What does GAPDH do?
a. GAPDH converts GAP into 1,3BPG
b. Also produces NADH employed in other reactions
c. Reaction occurs in two stages
i. Exergonic stage: oxidation of aldehyde to make carboxylic acid
ii. Endergonic stage: joining of carboxylate acid orthophosphate
16. What does phosphoglycerate kinase do?
a. Phosphoglycerate kinase transfers high energy phosphate of 1,3BPG to ADP to form ATP
b. Formation of ATP in this manner is called substratelevel phosphorylation c. Since two GAP molecules are input into stage 2 of glycolysis, two ATPs are produced replacing those consumed in stage 1
17. How is ATP output?
a. Phosphoglycerate mutase shifts the position of the phosphoryl group b. Enolase carries out a condensation reaction to produce the unstable PEP
c. PEP has the highest phosphate transfer potential of any molecule found in living cells
d. Pyruvate kinase then irreversibly transfers the phosphoryl group to ATP and forms pyruvate
e. Since two PEP molecules are produced for each glucose, this step produces a gain of two ATPS
18. What drives formation of unstable PEP?
a. Enolase forms PEP in a reaction that is powered by oxidation of 2 phosphoglycerate
b. Part of this energy is used to power the formation of ATP from ADP 19. What two main functions does glycolysis accomplish?
a. ATP generation
b. Building block for biosynthesis reactions
20. Glycolysis is regulated at irreversible reactions by what three allosteric enzymes? a. PFK
c. Pyruvate kinase
21. How does regulation work in muscles?
a. Muscles require ATP to power contraction
b. Glycolysis is stimulated when the energy charge falls
c. Phosphofructokinase: the most important control site
i. PFK has an ATP binding site away from the catalytic site
ii. ATP binding lowers affinity for fructose 6phosphate
iii. AMP competes for binding site with ATP, but does not inhibit fructose 6 phosphate binding
iv. PFK is more inhibited as ATP/AMP ratio increases
v. Low pH (e.g. from lactic acid fermentation) also inhibits PFK
22. How does hexokinase regulation in muscles work?
a. Inhibited by its own product glucose 6phosphate
b. If PFK is inhibited, glucose 6phosphate also builds up to inhibit hexokinase 23. How does pyruvate kinase regulation in muscle work?
a. Inhibited by ATP
b. Activated by fructose 1,6bisphosphate so that it can respond to high PFK turnover
c. An example of feedforward stimulation
24. What are the functions of the liver?
a. Maintaining bloodglucose levels through glycogen storage and glucose release b. Uses glucose to generate reducing power for biosynthesis
c. Building blocks for biosynthesis
d. The liver regulated glycolysis in a more complicated way than skeletal muscle
e. The liver waits its turn before activating glycolysis pathways to make sure that the brain and muscles have enough energy
25. How does PFK in the liver work?
a. PFK can still be inhibited by ATP and pH in the liver, but these compounds are more stable in the liver
b. PFK in the liver is inhibited by citrate, an early intermediate in the citric acid cycle
c. Fructose 2,6bisphosphate: signaling molecule used to regulate bloodglucose level
d. [F2,6BP] increases when [F6P] increases
e. F2,6BP increases PFK affinity for F6P and reduces the inhibitory effect of ATP
f. An example of feedforward stimulation
26. How does glucokinase in the liver work?
a. In the liver, glucokinase replaces most of the hexokinase
b. Glucokinase is an isozyme or isoenzyme for hexokinase
c. Isozymes: enzymes encoded by different genes with different amino acid sequences, yet catalyze the same reaction
d. Glucokinase has a KM 50x higher than that of hexokinase, which ensures that the liver only begins processing glucose at very high concentrations
27. How does pyruvate kinase in liver?
a. Pyruvate kinase has two isozymes: L for liver and M for muscle (and brain) b. The L form has additional regulatory behavior compared to the M form c. High concentrations of alanine inhibit the L form
d. pyruvate is used to synthesize alanine
e. The L form can be inactivated via phosphorylation, which is used to respond to low bloodglucose levels
28. What are glucose transporters?
a. Glycolysis is also regulated by transport of glucose into the cell
b. We can define a KM for transporters that defines the substrate concentration at which transport is at half its maximum rate
c. In the body, [glucose] = 4 mM to 8 mM
29. How do glucose transporters and cancer?
a. Cancer cells reproduce rapidly and thus are very metabolically active b. Many tumors will show enhanced rates of glucose uptake and glycolysis
c. Tumors also convert pyruvate to lactate, lowering the pH and possibly preventing immune system detection
d. Using a glucose analogue with a radioactive tracer, it is possible to visualize glucose uptake at tumors (T) in a PET scan
30. What are glycoconjugates?
a. Trojan horse strategy
b. Conjugate a drug to glucose to deliver chemotherapy directly to cancer cells 31. What are antisense oligonucleotides?
a. Transition blocking
b. Use a sequence antisense to GLUT1 mRNA to stop it from being translated
Chapter 16: Glycolysis (Part 2)
1. How is NAD+ regenerated?
a. During glycolysis, 2 NAD+ are consumed in GAPDH reaction (GAP to 1,3BPG) b. NAD+ is derived from the vitamin niacin and thus it cannot be synthesized by humans
c. NAD+ is regenerated through the metabolism of pyruvate
2. What are fermentations?
a. ATPgenerating processes in which organic compounds act as both donors and acceptors of electrons
b. Energy releasing metabolic process that is anaerobic (no oxygen)
c. Ethanol is formed from pyruvate in yeast and other microorganisms
3. How is ethanol fermented?
a. Glucose is converted into ethanol, CO2, water and ATP during ethanol fermentation
b. Alcoholic fermentation is a key component in brewing and winemaking c. There is not net oxidationreduction converting glucose to ethanol
4. How is lactic acid fermented?
a. A variety of microorganisms carry out lactic acid fermentation
b. Reaction also has not net oxidationreduction
5. Are other sugars besides glucose involved in glycolysis?
a. Sugars other than glucose can be diverted into glycolysis
b. Galactoseglucose interconversion pathway converts galactose into glucose 6 phosphate
6. What are the steps of galactose into glucose?
a. Stage 1: add a phosphate to galactose
b. Stage 2: produce glucose 1phosphate via UDPglucose
c. Stage 3: glucose 1phosphate is isomerized to glucose 6phosphate
d. Glucose 6phosphate can then be used in the 2nd step of glycolysis
7. How is fructose added into glycolysis?
a. Much fructose is converted in the liver
b. Fructokinase converts fructose to fructose 1phosphate
c. An aldolase splits F1P into glyceraldehyde and DHAP
d. Glyceraldehyde is then converted into GAP via triose kinase
8. How is fructose related to diet?
a. Overconsumption of sugar is a common problem in modern diets
b. Excessive fructose consumption has been implicated in obesity, fatty liver and insulin insensitivity
c. These effects are undergoing further study, but we do know that fructose is metabolized differently than glucose
d. In the liver, fructose can skip crucial PFK regulatory step of glycolysis e. Fructose is preferentially metabolized to fatty acid in the liver
Chapter 17: Gluconeogenesis
1. What is gluconeogenesis?
a. The synthesis of glucose from noncarbohydrate precursors
2. What is the main source of energy for the brain?
a. Glucose is the main source of energy for the brain and the sole source for red blood cells
b. The whole body needs about 160 g of glucose each day and 75% is used by the brain
c. Glucose/glycogen stores cover only ~1 day of use
d. The liver is the main site of gluconeogenesis with a small amount occurring in the kidney
3. What is the delta G of glycolysis?
a. The 10 chemical reactions provide ΔG = 90 kj/mol under physiological conditions
4. What is the most drastically different component of gluconeogenesis? a. Reverting pyruvate to PEP
b. The crucial intermediate in this process is oxaloacetate
5. How is pyruvate converted to oxaloacetate?
a. Pyruvate carboxylase employs biotin as a covalently attached prosthetic group
b. Biotin effectively carries CO2 from from one active site to another in the pyruvate carboxylase
c. Conversion takes place in the mitochondria
6. What is pyruvate carboxylase?
a. A multifunctional enzyme composed of four identical subunits
b. Each subunit has four different domains
c. Biotin attaches to a lysine in the biotin carboxyl carrier protein (BCCP) domain
d. CO2 attaches to the biotin the active site of biotin carboxylase
e. Acetyl CoA must be bound to the enzyme for reaction to occur
7. How does BCCP swing biotin?
a. The carboxylated biotin on the BCCP then swings 75 A across enzyme to reach the pyruvate carboxylase domain
b. Pyruvate carboxylase transfers the biotin CO2 to pyruvate
8. How is oxaloacetate exported to the cytoplasm?
a. Oxaloacetate is reduced to malate by malate dehydrogenase in the mitochondrion b. The malate is transported across mitochondrial membrane
c. Malate is reoxidized to oxaloacetate by an NAD+ linked malate dehydrogenase in the cytoplasm
9. How does oxaloacetate go to PEP?
a. Oxaloacetate is simultaneously decarboxylated and phosphorylated to generate PEP by phosphoenolpyruvate carboxykinase (PEPCK)
b. A GTP is consumed in the reaction
10. How does pyruvate go to PEP free energy?
a. Conversion of pyruvate to PEP is a highly endergonic reaction
b. Oxaloacetate is used as a carboxylated intermediate to make the full reaction thermodynamically favorable
c. Coupling decarboxylation of oxaloacetate to phosphorylation provides sufficient free energy to enable formation of unstable PEP
d. Decarboxylations often drive reactions that are otherwise highly endergonic
e. Once PEP is made, reactions can proceed in reverse direction through until dephosphorylation of F1,6BP — the next irreversible reaction in the pathway.
11. How does F1,6BP go to F6P?
a. Fructose 1,6bisphosphatase carries out a hydrolysis reaction to generate fructose 6phosphate
b. Fructose 6phosphate is readily converted glucose 6 phosphate
c. Glucose 6phosphate is the end point compound in most tissues
12. How is free glucose generated?
a. Generation of free glucose occurs mainly in the liver Glucose 6phosphatase in the ER carries out reaction
b. Transporters transport reactants and products in and out of ER lumen
13. How is gluconeogenesis regulated?
a. Gluconeogenesis and glycolysis are reciprocally regulated
b. They are understandably not active at the same time
14. How are things regulated in the liver?
a. Most compounds have opposing effects on the two pathways
b. Reciprocal regulation only occurs at two main points:
d. Pyr. Kinase/Pyr. CarbPEPCK High energy charge = High ATP
e. Low energy charge = High AMP, High ADP
f. High citric acid cycle = High citrate, High Acetyl CoA
g. F2,6BP regulates gluconeogenesis but F1,6BP does not
15. How is blood glucose regulated?
a. One function of the liver is to keep bloodglucose levels stable
b. The hormones insulin and glucagon are used to signal bloodglucose levels
c. PFK2 and FBPase2 are actually two domains of the same multifunctional enzyme PFK2/FBPase2
d. A third domain on the Nterminus is a regulatory domain that can be phosphorylated reversibly
e. PFK2/FBPase2: If phosphorylated, then will remove phosphates (FBPase2) If dephosphorylated, then will add phosphates (PFK2)
16. How are products used elsewhere?
a. Fast twitch skeletal muscles that lack oxygen will generate ATP by converting pyruvate to lactate
b. This lactate is used in other cells in two ways:
i. cardiac muscle and slowtwitch skeletal muscles will convert lactate back to pyruvate to generate ATP
ii. Cori Cycle: The liver converts the lactate produced by these muscle cells back into glucose via gluconeogenesis