Exam 4 Biochem

How does the presence of alpha-bonds versus beta-bonds influence digestibility of glucose polymers by humans?

Humans can digest glucose polymers containing alpha-bonds not beta. Therefore, glycogen and starch are digestible, whereas cellulose is not. Also, cellulose is fibrous rather than branched, which makes polymer insoluble in water and inaccessible to digestion in humans

How does increase in ADP/ATP ratio affect activity of isocitrate dehydrogenase?

If more ADP than ATP = cells needs energy = favors rxn of citric acid cycle, activates isocitrate dehydrogenase, stimulates formation of NADH and FADH2 for ETC

How does increase in NADH/NAD+ ratio affect activity of pyruvate dehydrogenase?

If more NADH than NAD+ = cell completed number of energy releasing rxns = less need for citric acid cycle to be active = decrease activity of pyruvate dehydrogenase

What is the metabolic basis for the observation that many adults cannot ingest large quantities of milk without developing gastic difficulties?

In some cases, enzyme that degrade lactose to glucose and glactose is missing. In other cases, the enzyme isomerizes galactose to glucose for further metabolic breakdown

You are a teaching assistant in a genchem lab. next experiment is oxidation-reduction titration involving iodine. You get starch indicator from stockroom. Why?

Iodine is reagent that will be added to reaction mixture in titration. When end point is reached, next drop of iodine will produce a characteristic blue color in presence of indicator

What is the difference between isomerase and mutase?

Isomerase is general term for enzyme that changes form of substrate without changing its empirical formula Mutase is enzyme of isomerase class that moves functional group, such as phosphate to new location in substrate molecule

Why would enzymes be found as isozymes?

Isozymes allow for subtle control of enzyme to respond to different cellular needs Lactate to pyruvate in liver, but reverse in muscle

Define isozymes and give example:

Isozymes are oligomeric enzymes that have slightly different amino acid compositions in different organs Lactate dehydrogenase or phosphofructokinase

In metabolism, glucose-6-phosphate can be used for glycogen synthesis or for glycolysis. What does it cost, in terms of ATP equivalents, to store G6P as glycogen, rather than use it for energy in glycolysis? Hint: branched structure of glycogen leads to 90% of glucose residues being released as glucose-1-phosphate and 10% as glucose

It "costs" one ATP equivalent (UTP to UDP) to add a glucose residue to glycogen. In degradation, about 90% of glucose residues do not require ATP to produce glucose-1-phosphate. Other 10% require ATP to phosphorylate glucose, around .1 ATP. Thus, overall cost is 1.1 ATP, compared with 3 ATP that can be derived from G6P

Several enzymes of glycolysis fall into classes that we will see often in metabolism. What reaction types are catalyzed by each: Kinases, isomerases, aldolases, dehydrogenases

Kinases - using high-energy phosphate to phosphorylate a substrate Isomerases - changing form of molecule without changing its empirical formula (replacing one isomer with another) Aldolases - performing aldol cleavage of sugar to yield two smaller sugars or sugar derivatives Dehydrogenases - changing oxidation state of substrate by removing hydrogens while simultaneously changing oxidation state of coenzyme

Briefly describe dual role of lipoic acid in pyruvate dehydrogenase complex:

Lipoic acid plays role in both redox and acetyl-transfer reactions

Why is acetyl-CoA considered central molecule of metabolism?

Many compounds can form acetyl-CoA, such as fats, carbs, amino acids Acetyl-CoA can also form fats and ketone bodies and feed directly into citric acid cycle

Free-energy change for oxidation of cytochrome aa3 complex by molecular oxygen is 102.3kJ = -24kcal for each mole of electron pairs transferred. What is maximum number of moles of ATP that could be produced in process? How many moles of ATP are actually produced? what is the efficiency of process, expressed as %?

Max yield = 3.35 ATP One ATP is actually produced, so efficiency = 33.3%

What electron acceptors play role in citric acid cycle?

NAD+ and FAD are primary electron acceptors of citric acid cycle

What 3 molecules produced during citric acid cycle are indirect or direct source of high-energy compounds?

NADH and FADH2 and indirect sources of energy produced in TCA cycle. GTP is direct source of energy

Why is citric acid cycle considered part of aerobic metabolism, even though molecular oxygen does not appear in any reaction?

NADH and FADH2 produced by cycle are electron donors in ETC which is linked to oxygen

Which of the enzymes discussed in this chapter are NADH-linked dehydrogenases?

NADH-linked dehydrogenases: Glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, and alcohol dehydrogenase

How does pentose phosphate pathway resond to cell's need for ATP, NADPH, ribose-5-phosphate?

NADPH: all rxns of pathway take place If cell needs ribose-5-phosphate, oxidative portion of pathway can be bypassed, only nonoxidative reshuffling rxns take place Pentose pathway does not have sig effect on cell's supply of ATP

What should be the net ATP yield for glycolysis when fructose, mannose, and galactose are sued as starting compounds?

Net yield of ATP form glycolysis is same when either of three substrates is used. energetics of conversion of hexoses to pyruvate are same, regardless of hexose type

Why is the rxn catalyzed by citrate synthase considered condensation rxn?

New carbon-carbon bond is formed

Electron transport and oxidative phosphorylation same process? Why or why not?

No, electron transport requires respiratory complexes of inner mitochondrial membrane. Oxidative phosphorylation requires ATP synthase. ETC can take place in absence of oxidative phosphorylation

Two sugars are epimers of each other. Is it possible to convert one to the other without breaking covalent bonds?

No; converting sugar to epimer requires inversion of configuration at chiral center

NADH is important coenzyme in catabolic processes, whereas NADPH appears in anabolic processes. Explain how exchange of two can be effected:

Oxaloacetate + NADH + H+ -> Malate + NAD+ Malate + NADP+ -> Pyruvate + CO2 + NADHPH + H+

What is approximate P/O ratio that can be expected if intact mitochondria are incubated in presence of oxygen, along with added succinate?

P/O 1.5 expected because oxidation of succinate passes electrons to coenzyme Q via flavoprotein intermediate, bypassing first complex

Describe multiple ways that PDH is controlled

PDH controlled allosterically Inhibited by ATP, acetyl-CoA, NADH PDH kinase phosphorylates PDH = inactive removing phosphate wit PDH phosphatase = reactivates it

Polysaccaride

Polymer of simple sugars, which are compounds that contain single carbonyl group and several hydroxyl groups

What is metabolic purpose of lactic acid production?

Purpose of step is to reduce pyruvate so that NADH can be oxidized to NAD+ which is needed for step catalyzed by glyceraldehyde-3-phosphate dehydrogenase

What are the possible metabolic fates of pyruvate?

Pyruvate can be converted to lactate, ethanol, or acetyl-CoA

how many enzymes are involved in mammalian pyruvate dehydrogenase? What are their functions?

Pyruvate dehydrogenase transfers a two-carbon unit to TPP and releases CO2 Dihydrolipoyl transacetylase transfers 2-carbon acetyl unit to lipoic acid and then to coenzyme-A Dihydrolipoyl dehydrogenase reoxidizes lipoic acid and reduces NAD+ Pyruvate ehydrogenase kinase phosphorylates PDH PDH phosphatase removes the phosphate

What is advantage of having Q cycle in electron transport in spite of complexity?

Q cycle allows for smooth transition from two-electron carriers (NADH and FADH2) to one-electron carriers (cytochromes)

Is the reaction of 2-phosphoglycerate to phosphoenolpyruvate a redox reaction?

Reaction of 2-phosphogylcerate to phosphoenolpyruvate is a dehydration rather than redox

List rxns of electron transport that liberate enough energy to drive phosphorylation of ADP:

Reactions of Complex I, transfer to coenzyme Q, reactions of complex III, Q cycle reactions, transfer to cytochrome c, reactions of complex IV

Which reaction or reactions that we have met in this chapter require ATP? Which reaction or reactions produce ATP? Enzymes that catalyze reactions that require and produce ATP?

Require: - phosphorylation of glucose to give G-6-P - phosphorylation of F-6-P to give fructose-1,6,-bisphosphate Produce: - transfer of phosphate group from 1,3-bisphosphoglycerate to ADP - transfer of phosphate group form phosphoenolpyruvate to ADP Enzymes for rxn that require: - hexokinase - glucokinase - phophofructokinase Enzymes for rn that produce: - phosphoglycerate kinase - pyruvate kinase

Which rxn in chapter 18 require ATP? Which rxn(s) produce ATP? List enzymes that catalyze rxns that require and that produce ATP:

Require: formation of UDP-glucose from glucose-1-phosphate and UTP, regneration of UTP, carboxylation of pyruvate to oxaloacetate Produce: none Enzymes that catalyze requiring rxn: UDP-glucose phosphorylase, nucleoside phophate kinase, pyruvate carboxylase Enzymes that catalyze producing rxn: none

Concentration of lactate in blood rises sharply during sprint and declines slowly for about hour afterward. What causes rapid rise in lactate concentration? What causes decline in lactate concentration after run?

Sprint is essentially anaerobic and produces lactate from glucose by glycolysis. Lactate is the recycled to glucose by gluconeogenesis

Suggest reason why sugar nucleotides, such as UDPG, play role in glycogen synthesis, rather than sugar phosphates, such as G6P

Sugar nucleotides are diphosphates. Net result is hydrolysis to two phosphate ions, releasing more energy and driving addition of glucose residues to glycogen in direction of polymerization

Reducing sugar

Sugar that has free aldehyde group. Aldehyde is easily oxidized, thus reducing oxidizing agent

Name two control mechanisms that play role in glycogen biosynthesis. Give example of each:

Synthesis is INactivated by phosphorylation and activated by dephosphorylation Allosterically inhibited by ATP and activated by G6P substrate As [ATP] increases, it binds to synthase causes conformational change, so higher concentration of G6P is required. Ensures that there is not only sufficient energy for glycogen storage - but also sufficient glucose

What are some of the main differences between the cell walls of plants and those of bacteria?

The cell wall of plants consist mainly of cellulose Cell walls of bacteria consist mainly of polysaccharides with peptide crosslinks

How does pyruvate from glycolysis get pyruvate dehydrogenase complex?

There is transporter on inner mitochondrial matrix that allows pyruvate from cytosol to pass into mitochondria

Briefly discuss role of thiamine pyrophosphate in enzymatic reactions:

Thiamine pyrophosphate is coenzyme in transfer of two-carbon units. It is required for catalysis by pyruvate decarboxylase in alcohol fermentation

Beriberi is a disease caused by deficiency of vitamin B1 (thiamine) in diet. Thiamine is precursor of thiamine pyrophosphate. Why is it not surprising that alcoholics tend to develop this issue?

Thiamine pyrophosphate is coenzyme required in reaction catalyzed by pyruvate carboxlase. Because rxn is part of metabolism of ethanol, less will be available to serve as coenzyme in reactions of other enzymes that require it

How does the cyclization of sugars introduce a new chiral center?

Two different orientations with respect to the sugar ring are possible for the hydroxyl group at the anomeric carbon. The two possibilities give rise to the new chiral center

What is metabolic advantage of having both hexokinase and glucokinase to phosphorylate glucose?

Two enzymes can have different tissue locations and kinetic parameters. Glucokinase has higher Km for glucose Thus, under low glucose: liver does not convert glucose to G-6-P. Under high glucose, glucokinase helps phosphorylate glucose so it can be stored as glycogen

Why is it essential that the mechanisms that activate glycogen synthesis also deactivate glycogen phosphorylase?

Two pathways occur in same cellular compartment, and if both are on at same time, futile ATP hydrolysis cycle results. Using same mechanism to turn them on/off is highly efficient

At what point in glycolysis are all the reactions considered doubled?

When aldolase splits fructose-1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate

Many soft drinks contain citric acid as sig part of flavor. Is this a good nutrient?

Yes, citric acid completely degraded to CO2 and water but readily absorbed into mitochondria

Would you expect delta G for hydrolysis of thioester be: a. large and negative b. large and positive c. small and negative d. small and positive

a. thioester are "high-energy" compounds

what yield of ATP can be expected form complete oxidation of each of the following substrates by reactions of glycolysis, citric acid cycle, and oxidative phosphorylation? a. Fructose-1,6-bisphosphate b. Glucose c. Phosphoenolpyruvate d. Glyceraldehyde-3-phosphate e. NADH f. Pyruvate

a. 34 b. 32 c. 13.5 d. 17 e. 2.5 f. 12.5

What is effect on gluconeogenesis and glycogen synthesis of (a) increasing level of ATP, (b) decreasing concentration of fructose-1,6-bisphosphate, and (c) increasing concentration of fructose-6-phosphate

a. favors both gluconeogensis and glycogen synthesis b. tend to stimulate glycolysis, rather than gluconeogenesis or glycogen synthesis c. levels of f-6-p do not have marked regulatory effect on these pathways of carbohydrate metabolism

glycosidic bond/linkage

acetal linkage that joins two sugars

How does fructose-2,6-bisphosphate play role as allosteric effector?

activator of phosphofructokinase and inhibitor of fructose-1,6-bisphosphatase

Name which, if any, of the following groups are not aldose-ketose pairs: D-ribose and D-ribulose D-glucose and D-fructose D-glyceraldehyde and dihydroxyacetone

all groups are aldose-ketose pairs

Explain how fructose-2,6-bisphosphate can play role in more than one metabolic pathway:

allosteric activator of phosphofructokinase (glycolytic enzyme) and inhibitor of fuctose-1,6-bisphophatase (enzyme in gluconeogenesis)

What is advantage of having mobile electron carriers in addition to large membrane-bound complexes of carriers?

allows electron transport to use most readily available complex rather than use same one all the time

How many ATPs can be produced from one molecule of glucose anearobically? Aerobically?

anaerobically: 2 ATPs Aerobically: 30-32 depending on tissue

Most hunters know that meat from animals that have been run to death taste sour. Explain why

animal that have been run to death have accumulated large amounts of lactic acid in muscle tissue

Briefly summarize main arguments of chemiosmotic coupling hypothesis:

based on difference in hydrogen ion concentration between intermembrane space and matrix of actively respiring mitochondria; flow of H ions back through channel in ATP synthase directly coupled to phosphorylation of ADP

What is the role of biotin in gluconeogenesis?

biotin is molecule to which CO2 is attached to process of being transferred to pyruvate. rxn produces oxaloacetate

What does the material of this chapter have to do with beer? what does i have to do with tired and aching muscles?

bubbles in beer are CO2, produced by alcoholic fermentation. Tired and aching muscles are caused in part by buildup of lactic acid, product of anaerobic glycolysis

What rxn require biotin

carboxylation of pyruvate to oxaloacetate

In what part of the cell does citric acid cycle take place? Does this differ from part of cell where glycolysis occurs?

citric acid cycle in mitochondrial matrix, glycolysis in cytosol

What are the different names used to describe pathway discussed in chapter 19?

citric acid cycle, Krebs cycle, TCA (Tricarboxylic acid) cycle

Oligosaccharides

compound formed by linking several simple sugars by glycosidic bonds

How can synthesis and breakdown of fructose-2,6-bisphosphate be controlled independently

concentration depends on balance between its synthesis and its breakdown. Separate enzymes that control formation and breakdown are themselves controlled by phosphorylation and dephosphorylation

What is the metabolic advantage in conversion of glucose to lactate, in which there is no net oxidation or reduction?

conversion of glucose to lactate rather than pyruvate recycles NADH

Why are unique reactions of glyoxylate cycle?

conversion of isocitrate to succinate glyoxylate catalyzed by isocitrate lyase conversion of glyoxylate and acetyl-CoA to malate catalyzed by malate synthase

In which steps of aerobic processing of pyruvate are reduced electron carriers produced?

conversion of pyruvate to acetyl-CoA Conversion of isocitrate to alpha-ketoglutarate conversion of alpha-ketoglutarate to succinyl-CoA conversion of succinate to fumarate conversion of malate to oxaloacetate

In which steps of aerobic processing of pyruvate is CO2 produced?

conversion of pyruvate to acetyl-CoA, conversion of isocitrate to alpha-ketoglutarate, and conversion of alpha-ketoglutarate to succinyl-CoA

Furanose

cyclic sugar, five-membered ring

Pyranose

cyclic sugar, six-membered ring

Two biochem students are about to use mitochondria isolated from rat liver for experiment on oxidative phosphorylation. Directions specify addition of purified cytochrome c form any source to reaction mixture. Why is added cytochrome c needed? why does source not have to be same as that of mitochondria?

cytochrome c is not tightly bound to mitochondrial membrane and can easily be lost in course of cell fractionation. Protein is similar in most aerobic organisms that cytochrome c from one source can easily be substituted for that from another source

How do cytochromes differ from hemoglobin and myoglobin in terms of chemical activity?

cytochromes are proteins of electrons transport; heme ion alternates between Fe(II) and Fe(III) states while heme in myoglobin and hemoglobin stays in Fe(II) state

Why is different reducing agent (NADPH) used in anabolic rxns rather than NADH, which plays roe in catabolic ones?

different reducing agents keeps pathways separate metabolically, thus subject to independent control and do not waste energy

Would eating candy bars, high in sucrose rather than complex carbs, help build up glycogen stores?

disaccharides sucrose can be hydrolyzed to glucose and fructose, which can both be readily be converted to glucose-1-phosphate, the immediate precursor of glycogen. Not usual form of "glycogen-loading"

Briefly outline role of UDPG in glycogen biosynthesis

each glucose residue is added to growing glycogen molecule by transfer from UDPG

Why would you expect to see rxn of substrate cycles invovle different enzymes for different directions?

enzymes speed up forward and reverse rxn at same extent. Having different catalysts is only way to ensure independent control over rates of forward and reverse

Why is it reasonable to expect G-6-P will be oxidized to lactone rather than to open-chain compound?

ester bond is more easily broken than any of other bonds that form sugar ring. Hydrolysis of bond is next step in pathway

Why is the formation of fructose-1,6-bisphosphate a step in which control is likely to be exercised in glycolytic pathway?

formation of fructose-1,6-bisphosphate is committed step in glycolytic pathway. It is also one of energy-requiring steps of pathway. Control is exercised here

Define substrate-level phosphorylation and give example:

free energy of hydrolysis of a substrate is energetic driving force in substrate-level phosphorylation glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate

Define P/O ratio and indicate why it is important?

gives number of moles of Pi consumed in reaction ADP + Pi -> ATP for each mole of oxygen atom consumed in 1/2 O2 + 2H+ ->2H2O; measure of coupling of ATP production to electron transport

How does control of glucose-6-phosphatase reaction differ from that of fructose-1,6-bisphosphatase reaction?

glucose-6-phosphatase: concentration of substrate is main determinant of reaction velocity Fructose-1,6-bisphosphatase: allosteric effects are main determinant of reaction velocity

Is glycogen synthase reaction exergonic or endergonic? why

glycogen synthase reaction is exergonic overall because it is coupled to phosphate ester hydrolysis

What role does proton gradient play in chemiosmotic coupling?

gradient is related to ATP production gradient leads to conformational change in number of proteins, releasing tightly bound ATP from synthase

How does glycolysis yield of ATP differ form gross yield of ATP?

gross yield is four ATP per glucose molecule, but reactions of glycolysis require two ATP per glucose

Why is it advantageous for two control mechanisms - allosteric control and covalent modification - to be involved in metabolism of glycogen?

having two control mechanisms allows for fine-tuning of control and for possibility of amplification. Both mechanisms are capable of rapid response to conditions, miliseconds in case of allosteric control and seconds to minutes in case of covalent modification

blood samples for research or medical tests sometimes have heparin added. Why is this done?

heparin is anticoagulant, its presence prevents blood clotting

How do glucokinase and hexokinase differ in function?

hexokinase: add phosphate group to any 6-carbon sugar, usual enzyme for phosphorylating 6-carbon sugars glucokinase: specific for glucose, has lower affinity for glucose, tends to deal with excess of glucose (particularly in liver)

How does hydrolysis of fructose-1,6-bisphosphate bring about reversal of one of physiologically irreversible steps of glycolysis?

hydrolysis of fructose-1,6-bisphosphate is strongly exergonic. Reverse reaction in glycolysis, phosphorylation of fructose-6-phosphate is irreversible because energy supplied by ATP hydrolysis

How does role of G-6-P in gluconeogenesis differ from that in glycolysis?

in gluconeogenesis G-6-P is dephosphorylated to glucose, last step in pathway In glycolysis, it isomerizes to F-6-P, early in pathway

How does phosphorolysis differ from hydrolysis?

in phosphorolysis, bond is cleaved by adding elements of phosphoric acid across bond in hydrolysis, cleavage takes place by adding elements of water across bond

What are the metabolic effects of not being able to produce the M subunit of phosphofructokinase?

individuals who lack the gene that directs the synthesis of M form of enzyme can carry on glycolysis in their livers but experience muscle weakness because they lack the enzyme in muscle

What role does insulin play in glycogen synthesis?

insulin triggers series of events that leads to glycogen synthesis

You are planning to go on strenuous hike and are advised to eat plenty of high-carbohydrate foods for several days beforehand. WHY

intended to build up glycogen stores in body, glycogen will be available to supply required energy

Which enzymes of citric acid cycle are missing from glycooxylate cycle?

isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinyl-CoA synthetase

How does mitochondrial structure contribute to aerobic metabolism, particularly to integration of citric acid cycle and electron transport?

it confines reduced electron carries produced by citric acid cycle to matrix.

Why does Cori cycle take place in liver and in muscle?

muscle tissues use large quantities of glucose, producing lactate. Liver is important site of gluconeogenesis to recycle lactate to glucose

why does ATP production require intact mitochondrial membrane?

necessary for compartmentalization, which is necessary for proton pumping

Does net gain of ATP in glycolysis differ when glycogen, rather than glucose, is starting material? if so, what is change?

net gain of 3, rather than 2, ATP when glycogen, not glucose, is starting material of glycolysis

What is net gain of ATP molecules derived form reactions of glycolysis?

net gain of two molecules ATP molecules per glucose molecule consumed in glycolysis

Avidin, protein found in egg whites, binds to biotin so strongly that it inhibits enzymes that require biotin. What is effect on glycogen formation? on gluconeogenesis? on pentose phosphate pathway?

only gluconeogenesis requires biotin. Pyruvate carboxylase is enzyme in question

Briefly describe role of uncouplers in oxidative phosphorylation:

overcome proton gradient on which oxidative phosphorylation depends

Why type of rxn is catalyzed by isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase

oxidative decarboxylations

Do any of respiratory complexes play role in citric acid cycle? if so, what is role?

part of complex II catalyzes conversion of succinate to fumarate in citric acid cycle

What is Cori cycle?

pathway in which cycling of glucose due to glycolysis in muscle and gluconeogenesis in liver. Blood transports lactate form muscle to liver and glucose form liver to muscle

What is meant by statement that a pathway is amphibolic?

pathway is involved in both catabolism and anabolism

If lactic acid is buildup product of strenuous muscle activity, why is sodium lactate often given to hospital patients intravenously?

problem with lactic acid is that it is an acid. H+ produced from lactic acid formation causes burning muscle sensation. Sodium lactate is conjugate weak base of lactic acid. It is reconverted to glucose by gluconeogenesis in liver. Giving sodium lactate intravenously is good way to supply an indirect source of blood glucose.

Why do electron-transfer reactions of cytochromes differ in standard reduction potential, even though all reactions involve same oxidation-reduction reaction of iron?

protein environment of iron differs in each of cytochromes, causing differences in reduction potentials

Which reactions in glycolysis are coupled reactions?

reactions catalyzed by hexokinase, phophofructokinase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerokinase, pyruvate kinase

Which reactions are the control points in glycolysis?

reactions catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase

Briefly describe "going for the burn" in workout:

refers to sensation that accompanies lactic acid buildup

What does it mean when an enzyme has name synthase?

rxn catalyzed produces product that is part of name and does not require direct input of energy from high-energy phosphate

With respect to stereochemistry, what is unique about rxn catalyzed by aconitase?

rxn involves achiral citrate being converted into chiral isocitrate

What are similarities and differences between rxns catalyzed by pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase?

rxn proceed by same mechanism and use same cofactors difference is initial substrate (pyruvate or alpha-ketoglutarate). During rxn pyruvate dehydrogenase shuttles acetyl unit while alpha-ketoglutarate dehydrogenase shuttles succinyl unit

Which steps of aerobic metabolism of pyruvate through citric acid cycle are control points?

rxns catalyzed by pyruvate dehydrogenase, citrate synthase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase

What role does glucagon and epinephrine play in glycogen breakdown

start chain events leading to glycogen breakdown

What would be the ATP yield per molecule of glucose in muscle if glycogen were source of glucose?

starting with glucose-1-phosphate, net yield is 3 ATP, because one of priming reactions is no longer used. Thus, glycogen is more efficient fuel for glycolysis than free glucose

Which steps in glycolysis are physiologically irreversible?

steps catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase

Earlier biochemists called substrate cycles "futile cycles", why? Why is it misnomer?

substrate cycles are futile because there is not net change except for hydrolysis of ATP. However, cycles allow for increased control over opposing reactions when they are catalyzed by different enzymes

What is the chemical difference between a sugar phosphate and a sugar involved in glycosidic bond?

sugar phosphate: ester bond is formed Glycosidic bond is acetal, which can be hydrolyzed to regenerate the two original sugar hydroxyls

Aldose

sugar that contains aldehyde group

Ketose

sugar that contains ketone group

Many NADH-linked dehydrogenases have similar active sites. Which part of glyceraldehyde-3-phosphate dehydrogenase would be the most conserved between other enzymes?

the part of active site that binds to NADH would be part that is most conserved since, many dehydrogenases use that coenzyme

malate-aspartate shuttle yields about 2.5 moles of ATP for each mole of cytosolic NADH. Why does nature use glycerolphosphate shuttle, which yields only about 1.5 moles of ATP?

transport product of malate-aspartate shuttle is NADH glycerol-phosphate shuttle is FADH2, can go against transmembrane NADH concentration gradient

Researcher claims to have discovered variant form of glycogen. variation is that is has very few branches and that the branches are only three residues long. Is it likely that this discovery will be confirmed by later work?

unlikely. Highly branched structure of glycogen is optimized for release of glucose on demand

Show how rxn of ETC differ when FADH2 is starting point:

when FADH2 is starting point, electrons are passed form FADH2 to coenzyme Q in rxn carried out by complex II that bypasses complex I

Most metabolic pathways are relatively long and appear to be very complex, why

with few exceptions, biochemical rxn typically results in only one chemical modification of substrate. Accordingly, several to many step are needed to reach ultimate goal

Discuss logic of nature of allosteric inhibitors and activators of glycolysis. Why would these molecules be use?

- ATP inhibitor of several steps; high levels of ATP means cell already has sufficient energy - G-6-P inhibits hexokinase (product inhibition), high G-6-P shows sufficient glucose is available form glycogen breakdown - phosphofructokinase inhibited by fructose-2,6-bisphosphate (levels controlled by hormones), citrate (which indicates sufficient energy from citric acid cycle) - pyruvate kinase inhibited by acetyl-CoA, presence indicates fatty acids are being used to generate energy for citiric acid cycle

Describe various purposes of citric acid cycle:

- central metabolic pathway - indirect producer of energy - receives fuel form other pathways and generates reduced electrons for ETC - involved in anabolism

Which steps of glycolysis are irreversible? What bearing does this observation have on reactions in which gluconeogenesis differs form glycolysis?

- production of pyruvate and ATP from phosphoenolpyruvate - production of fructose-1,6-bisphosphate from fructose-6-phosphate -production of glucose-6-phosphate from glucose - reactions are bypassed in gluconeogenesis; different reactions occur using different enzymes

What are two advantages of components of ETC being embedded in inner mitochondrial membrane?

1. if components were in solution, speed would be limited to rate of diffusion 2. componenets are properaly positioned to facilitate transort of protons ffrom matrix to intermembrane space

Do all respiratory complexes generate enough energy to phosphorylate ADP to ATP?

3 of 4 respiratory complexes generate enough energy to phosphorylate ADP to ATP. Complex II is sole exception

How many possible epimers of D-glucose exist?

4 - with inversion of configuration at a single carbon; possible at carbons 2 through 5

How many chiral centers are there in open-chain form of glucose? cyclic form?

4 chiral centers in open-chain cyclization introduces another chiral center in hemiacetal formation = 5 chiral centers in cyclic form

Calculate amount of ATP that ca be produced form one molecule of lactose metabolized aerobically through glycolysis and citric acid cycle:

60-64 ATP There is no energy cost in hydrolysis of bond between two monosaccharides, so essentially there are two hexoses to consider

What is fluoroacetate? why is it used?

A poison that is produced naturally in some plants and used as poison against undesirable pests. It is poisonous because it is used by citrate synthase to make fluorocitrate, which is inhibitor of citric acid cycle

How does action of allosteric effectors differ in reactions catalyzed by phosphorfructokinase and fructose-1,6-bisphosphatase?

AMP and fructose-2,6-bisphosphate are allosteric activators of phosphofructokinase and allosteric inhibitors of fructose-1,6-bisphosphate

What are the two most common inhibitors of steps of citric acid cycle and reaction catalyzed by pyruvate dehydrogenase?

ATP and NADH

How does ATP act as an allosteric effector in mode of action of phosphofurctokinase?

ATP inhibits phosphofructokinase, consistent with the fact that ATP is produced by later reactions of glycolysis

Explain origin of name of enzyme aldolase:

Aldolase catalyzes reverse aldol condensation of fructose-1,6,-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate

What do cytochromes have in common with hemoglobin or myoglobin?

All contain heme group

Name two forms of control enzymatic action. Which of two is more important in control of glycogen breakdown?

Allosteric effects and covalent modification. Covalent modification plays more important role in glycogen breakdown

Which pathways are involved in anaerobic metabolism of glucose? Which pathways are involved in aerobic metabolism of glucose?

Anaerobic glycolysis principal pathway for anaerobic; pentose phosphate pathway aerobic glycolysis and citric acid cycle are aerobic

Glycogen is highly branched. What advantage, if any, does this provide an animal?

Because of branching, the glycogen molecule gives rise to number of available glucose molecules at a time when it is being hydrolyzed to provide energy. A linear molecule could produce only one available glucose at a time

What is the main structural difference between cellulose and starch?

Both polymers of glucose Cellulose: monomers are joined by beta-glycosidic linkage Starch: monomers joined by alpha-glycosidic linkage

Show carbon atom that changes oxidation state during reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase. What is functional group that changes during the reaction?

Carbon-1 of glyceraldehyde is aldehyde group. It changes oxidation state to carboxylic acid, which is phosphorylated simulataneously

How does chitin differ from cellulose in structure and function?

Chitin is polymer of N-acetyl-beta-D-glucosamine, whereas cellulose is polymer of D-glucose. Both polymers play structural role, but chitin occurs in exoskeletons of invertebrates and cellulose primarily in plants

Why is the polysaccharide chitin a suitable material for the exoskeleton of invertebrate such as lobsters? What other sort of material can play similar role?

Chitin is suitable material for exoskeleton of invertebrates because of its mechanical strength. Individual polymer strands are cross-linked by hydrogen bonding, accounting for strength. Cellulose is another polysaccharide cross-linked in same way, and it can play similar role

Which of the following does not play role in respiratory complexes: cytochromes, flavoproteins, iron-sulfur proteins, coenzyme Q?

Coenzyme Q is not bound to any of respiratory complexes, moves freely in membrane

Name which, if any, of the following are epimers of D-glucose: D-mannose, D-galactose, D-ribose

D-mannose and D-galactose are both epimers of D-glucose, with inversion of configuration around carbon atoms 2 and 4, respectively D-ribose has only five carbons

Explain how minor structural differences between alpha and beta glucose is related to differences in structure and function in polymers formed from two monomers.

Differences in structure: cellulose consists of linear fibers, starch has coil form Differences in function: cellulose has structural role, but starch is used for energy storage

No animal can digest cellulose. Reconcile this statement with the fact that many animals are herbivores that depend heavily on cellulose as food source.

Digestive tract of these animals contain bacteria that have enzyme to hydrolyze cellulose

What is the source of the energy needed to incorporate glucose residues into glycogen? how is it used?

Each glucose residue added to growing phosphate chain comes from uridine diphosphate glucose. Cleavage of phosphate ester bond to nucleoside diphosphate moiety supplies the needed energy

Briefly summarize steps in ETC from NADH to oxygen:

Electron passed from NADH -> flavin-containing protein -> coenzyme Q -> cytochrome b -> cytochrome c (via Q cycle) -> cytochrom a and a3 -> oxygen

What is the difference between an enantiomer and diastereomer?

Enantiomers are nonsuperimposable, mirror-image stereoisomers Diastereomers are nonsuperimposable, nonmirrorimage stereoisomers

acetyl-CoA and succinyl-CoA are both high-energy thioesters, but their chemical energy is put to different uses. Why?

Energy released by hydrolysis of acetyl-CoA is needed for condensation rxn that links acetyl moiety to oxaloacetate, yielding citrate. Energy released by hydrolysis of succinyl-CoA drives phosphorylation of GDP to yield GTP

Why is it useful to have primer in glycogen synthesis?

Enzyme that catalyzes addition of glucose residues to growing glycogen chain cannot form bond between isolated glucose residues; need primer

Is it possible to have proton pumping in absence of electron transport?

Experiments with model systems have shown that electron transport and proton pumping can take place separately

Is mitochondrial ATP synthase an integral membrane protein?

F0 portion lies within membrane, but F1 project into matrix

In what sense is mitochondrial ATP synthase a motor protein?

F1 has stationary domain and domain that rotates

Describe role of F1 portion of ATP synthase in oxidative phosphorylation:

F1 portion of mitochondrial ATP synthase, which projects into matrix, is site of ATP synthesis

What is advantage to organization of PDH complex?

Five enzymes are all in close proximity for efficient shuttling of acetyl unit between molecules and efficient control of complex by phosphorylation

glycoprotein

Formed by covalent bonding of sugars to protein

Why is the formation of fructose-1,6-bisphosphate the committed step in glycolysis?

Fructose-1,6-bisphosphate can only undergo the reactions of glycolysis. Components of pathway up to this point can have other metabolic fates

Why are furanoses and pyranoses the most common cyclic forms of sugars?

Furanoses and pyranoses have five-membered and six-membered rings, respectively. It is well known from ochem that rings of this size are most stable and most readily formed

What are 4 possible metabolic fates of G-6-P?

Glucose (gluconeogenesis), glycogen, pentose phosphates (pentose phosphate pathway), pyruvate (glycolysis)

High levels of glucose-6-phosphate inhibited glycolysis. IF concentration of glucose-6-phosphate decreases, activity is restored. Why?

Glucose-6-phosphate inhibits hexokinase, enzyme responsible for its own formation. Because G-6-P is used up by additional reactions of glycolysis, inhibition is relieved

Why is it advantageous that breakdown of glycogen gives rise to glucose-6-phosphate rather than glucose?

Glucose-6-phosphate is already phosphorylated. This saves one ATP equivalent in early stages of glycolysis

How does glycogen differ from starch in structure and function?

Glycogen and starch differ mainly in degree of chain branching. Both polymers serve as vehicles for energy storage, glycogen in animals and starch in plants

How is it advantageous for animals to convert ingested starch to glucose and then incorporate glucose into glycogen?

Glycogen is more extensively branched than starch. It is more useful storage form of glucose for animals because glucose can be mobilized more easily when there is need for energy

What is the main structural difference between glycogen and starch?

Glycogen: highly branched polymer Starch: can have both linear and branched form (but not as branched as glycogen)

What are glycoproteins? What are some of their biochemical roles?

Glycoproteins are ones in which carbohydrates are covalently bonded to proteins. They play role in eukaryotic cell membranes, frequently as recognition sites for external molecules. Antibodies (immunoglobulins) are glycoproteins

Which molecules act as inhibitors of glycolysis? which molecules act as activators?

Hexokinase inhibited by glucose-6-phosphate Phosphofructokinase inhibited by ATP and citrate, stimulated by AMP and fructose-2,6-bisphosphate Pyruvate kinase inhibted by ATP, acetyl-CoA, and alanine, stimulated by AMP and fructose-1,6,-bisphosphate

In what way is the observed mode of action of hexokinase consistent with induced-fit theory of enzyme action?

Hexokinase molecule changes shape drastically on binding to substrate, consistent with induced-fit theory of enzyme adapting itself to its substrate