Carbohydrate Metabolism I

Question 1

Metabolic pathway utilized by cells to oxidize glucose to provide energy as atp

Answer 1

Glycolysis

Question 2

Why is the glycolytic pathway central to carb metabolism

Answer 2

b/c sugars whether obtained from the diet or from the breakdown of other substrates in the body, can eventually be chemically converted to glucose

Question 3

end product of glycolysis and where does it occur

Answer 3

end product is pyruvate and occurs in cells with mitochondria and aerobic glycolysis

Question 4

anaerobic glycolysis describe

Answer 4

pyruvate reduced to lactate and allows the production of ATP in tissues deprived of mitochondria (RBC, lens of eye) or in cells that lack sufficient 0xygen

Question 5

Preparatory phase (reactions of glycolysis) provide overview

Answer 5

conversion of glucose to pyruvate occurs in two phases. The first five reactions of glycolysis correspond to an energy investment phase in which the phosphrylated forms of intermediates are synthesized at the expense of atp

Question 6

phosphorylation of glucose - what happens

Answer 6

glucose is irreversibly phosphrylated in the cytosol as glucose 6 phosphate by the enzyme, hexokinase. this reaction effectively traps glucose P04 in the cytosol, committing it to further metabolism in the cell

Question 7

describe hexokinase 1-3

Answer 7

decrease km increase affinity for glucose , broad substratespecificity.
can phosphorylate other hexoses aside from glucose (broad substrate specificity)
have a low km and therefore high affinity for glucose. These properties allow efficient phosphorylation of glucose even when tissue conc of glucose are low

Question 8

describe hexokinase 4 (glucokinase)

Answer 8

Glucokinase. predominant enzyme present in liver parenchymal cells and beta cells of the pancreas, responsible for the phosphorylation of glucose. this isoenzyme has a higher km, requiring a higher glucose conc for half saturation. Therefore, it becomes functional only during period of elevated glucose conc in the hepatocytes such as after a car-rich meal

Question 9

glucokinase vs hexokinase: tissue distribution

Answer 9

H: all tissues
G: liver beta pancreatic cells

Question 10

glucokinase vs hexokinase: km

Answer 10

h: low, phosphorylates glucose even when tissue conc is low
G: high, prevents entry of large amounts of glucose in the circulation and minimizing hyperglycemia during the absorptive period.

Question 11

glucokinase vs hexokinase: vmax

Answer 11

h: low
g: high

Question 12

substrate

Answer 12

H: d glucose and other hexoses
g: d glucose only

Question 13

inhibition by cpu-6-p04

Answer 13

h: yes
g: no

Question 14

describe isomerization of glucose 6- phosphate

Answer 14

the isomerizatioin of glucose 6- phosphate to fructose 6-phosphate is catalyzed by phosphoglucose isomerase. rxn is readily reversible and is not a rate limiting nor regulated step

Question 15

most important control point in glycolysis

Answer 15

phosphorylation of fructose 6-phosphate - rate limiting and committed step in glycolysis

Question 16

phosphofructokinase-1 role

Answer 16

catalyzes the irreversible phosphorylation of fructose 6-phosphate

Question 17

activity of rate limiting enzyme pfk-1 controlled by energy level within the cell elaborate

Answer 17

energy level within the cell - high levels of tap in the cell allosterically inhibits pfk-1 activity. increased atp conc acts as an energy rich signal representing abundant levels of high energy compounds. conversely, high concentrations of amp, signaling depletion of the cells energy stores, allosterically activates pfk1 activity
regulatory substrates

Question 18

activity of rate limiting enzyme pfk-1 controlled by regulatory substrates: inhibits pfk 1

Answer 18

citrate intermediate of TCA - inhibits pfk-1.

Question 19

activity of rate limiting enzyme pfk-1 controlled by regulatory substrates: fructose 2,6 biphosphate

Answer 19

fructose 2,6 biphosphate most potent allosteric activator of pfk-1 that can oppose inhibition by high tap levels. it is formed by phosphorylation of fructose 6 p04 by pfk-2.
PFK 2

Question 20

activity of rate limiting enzyme pfk-1 controlled by regulatory substrates: pfk 2

Answer 20

a bifunctional protein that has both the kinase activity that produces fructose 2,6 biphosphatase activity that depphosphorylates fructose 2,6 biphosphate back to fructose 6 phosphate. In the liver the kinase domain is active if dephosphorylated and inactive if phosphorylated

Question 21

activity of rate limiting enzyme pfk-1 controlled by regulatory substrates: what happens after a car-rich meal (well fed state)

Answer 21

decreased levels of glucagon and elevated levels of insulin. cause an increase in fructose 2,6 biphosphate. and subsequently, increase in the rate of glycolysis in the liver.. so fructose 2,6 biphosphate acts as an intracellular signal, indicating that glucose is abundant.

Question 22

activity of rate limiting enzyme pfk-1 controlled by regulatory substrates: fasted state

Answer 22

elevated levels of glucagon and low levels of insulin, decrease the intracellular conc of hepatic fructose 2,6 biphosphate. the kinase domain of pfk2 is phosphorylated and is rendered inactive. this results in inhibition of glycolysis and activation of the reversal pathway, gluconeogenesis

Question 23

Cleavage of fructose 1,6 biphosphate

Answer 23

aldolase cleaves fructose 1,6 biphosphate to DHAP (dihydroxyacetone phosphate) and glyceraldehyde 3-phosphate. rxn is reversible and not regulated.

Question 24

isomerization of dihydroxyacetone phosphate - describe

Answer 24

triose phosphate isomerase interconverts dihydroxyacetone phosphate and glyceraldehyde 3 - phosphate. DHAP must be isomerized to glyceraldehyde 3-phosphate for further metabolism by the glycolyitic pathway. this isomerization results in the net production of 2 molecules of glyceraldehyde 3-phosphate

Question 25

isomerization of dihydroxyacetone phosphate: payoff phase

Answer 25

payoff phase includes the energy conserving phosphorylation steps in which some of the chemical energy of the glucose molecule is conserved in the form of ATP and nadh. it involves the subsequent reactions of glycolysis in which a net of 2 molecules of tap are formed by substrate - level phosphorylation per glucose molecule metabolized

Question 26

oxidation of glyceraldehyde 3-phosphate: first redox rxn of glycolysis

Answer 26

where glyceraldehyde 3-phopshate converted to 1,3 bpg (biphosphoglycerate) by glyceraldehyde 3 phosphate dehydrogenase

Question 27

oxidation of glyceraldehyde 3-phosphate: coupled to the attachment of pi to the carboxyl group? step

Answer 27

oxidation of the aldehyde group c1 of glyceraldehyde 3 phosphate to a carboxyl group is coupled to the attachment of pi to carboxyl group. The high energy phosphate group at c1 of 1,3 bog conserves much of the free energy produced by the oxidation of glyceraldehyde 3-phosphate. the energy of this high energy phosphate drives the synthesis of tap in the next rxn of glycolysis

Question 28

oxidation of glyceraldehyde 3-phosphate: 2 major mechanism oxidizing nadh

Answer 28

the nadh produced from this reaction must be deoxidized back to nad+ to replenish its limited supply in the cell. the 2 major mechanisms of oxidizing nadh are: conversion of pyruvate to lactate via lactate dehydrogenase (anaerobic glycolysis) oxidation of nadh via the ETC (aerobic glycolysis) b/c the innder mitochondrial membrane is impermeable to nadh, the reducing equivalents (2 electrons) of nadh are the transported into the mitochondrial matrix through the 2 substrate shuttles: glycerophosphate and maltase aspartate shuttle systems

Question 29

oxidation of glyceraldehyde 3-phosphate: Glycerophosphate shuttle

Answer 29

two electrons are transferred from NADH to dihydroxyacetone phosphate by cytosolic glycerol 3-phosphate dehydrogenase. The glycerol 3-phosphate produced is oxidized by the glycerol 3 phosphate dehydrogenase as FAD is reduced to fadh2. In the etc, fadh2 is oxidized back to fad. The glycerol phosphate shuttle therefore results in the synthesis of 2 taps for each cytosolic nadh oxidized. In short glycerophosphate shuttle for transfer of reducing equivalents from the cytosol into the mitochondrion

Question 30

oxidation of glyceraldehyde 3-phosphate: maltase aspartame shuttle

Answer 30

two electrons are transferred from nadh to oxaloacetate by cytosolic malate dehydrogenase. the malate produced is oxidized by mitochondrial malate dehydrogenase as NAD+ is reduced to nadh + H+. in the etc, nadh+ H+ is oxidized back to NAD+. the malate aspartate shuttle, therefore, results in the synthesis of three taps for each cytosolic nadh oxidized . In short, the malate aspartate shuttle for transfer of reducing equivalents from the cytosol into the mitochondrion

Question 31

oxidation of glyceraldehyde 3-phosphate: synthesis of 2,3 bisphosphoglycerate pathway in RBC

Answer 31

in the rbi, some of the 1,3 bog is converted to 2,3 bog by the action go bisphospoglycerate mutase. 2,3 bog formed in a shunt reaction in rbi glycolysis serves to increase oxygen delivery to the tissues . 2,3 bpg is hydrolyzed by a phosphatase to 3-phospoglycerate - also an intermediate in glycolysis

Question 32

Synthesis of 3-phosphoglycerate, producing ATP: reversible reaction

Answer 32

catalyzed by phosphoglycerate kinase. when 1,3 bog is converted to 3-phosphoglycerate, the high energy phosphate group of 1,2-bog is used to synthesize ATP from adp

Question 33

Synthesis of 3-phosphoglycerate, producing ATP: kinase rxn

Answer 33

b/c two molecules of 1,3 bpg are formed from each glucose molecule , this kinase reaction replaces the 2 tap molecules consumed by the earlier formation f glucose 6-p04 and fructose 1,6 bisphosphate during the energy investment phase of glycolysis

Question 34

Synthesis of 3-phosphoglycerate, producing ATP: formation of ATP

Answer 34

via substrate level phosphorylation , in which energy needed for the production of a high energy phosphate comes from a substrate rather than from the ETC

Question 35

shift of the phosphate group

Answer 35

reaction freely reversible and is catalyzed by phosphoglycerate mutase

Question 36

dehydration of 2-phosphoglycerate: formation of PEP

Answer 36

dehydration of 2-phosphoglycerate by enolase redistributes the energy within the substrate, resulting in the formation of PEP, which contains a high energy enol phosphate. reaction is reversible despite the high energy nature of the product

Question 37

formation of pyruvate, producing atp

Answer 37

conversion of pep to pyruvate is catalyzed by pyruvate kinase (pk). the third irreversible reaction of glycolysis. the high energy enol phosphate in PEP is used to synthesize ATP from ADP and is another example of substrate level phosphorylation

Question 38

dehydration of 2-phosphoglycerate: feedforward by fructose 1,6bisp04 regulation of PK activity

Answer 38

pk is activated by fructose 1,6bisphosphate the product of pfk-1 reaction . this feedforward regulation has the effect of linking the 2 kinase activities: increased pfk activity results in elevated levels of fructose 1,6 bisphosphate, which activates pk

Question 39

dehydration of 2-phosphoglycerate: covalent modification regulation of pk activity

Answer 39

phosphorylation by camp dependent protein kinase leads to inactivation of the hepatic isozyme of PK. when blood glucose levels are low (fasting state), elevated glucagon increases the intracellular cAMP, which causes the phosphorylation and inactivation of PK in the liver only. Therefore, pep is unable to continue in glycolysis and instead enters the gluconeogenesis pathway. this in part explains the observed inhibition of hepatic glycolysis and stimulation of gluconeogenesis by glucagon. dephospho rylation of pk by a phosphatase results in reactivation of the enzyme, leading to completion of glycolysis

Question 40

reduction of pyruvate to lactate: what is lactate

Answer 40

lactate formed by the action of lactate dehydrogenase is the final product of anaerobic glycolysis in eukaryotic cells. lactate formation is the major fate for pyruvate in the lens and cornea of the eye, kidney medulla, testes, leukocytes, and tbs bc there are all poorly vascularized and or lack mitochondria

Question 41

reduction of pyruvate to lactate: exercising muscle

Answer 41

nadh production by glyceraldehyde 3phosphate dehydrogenase exceeds the oxidative pathway of etc this results in an elevated nadh/nad+ ratio, favoring reduction of pyruvate to lactate

Question 42

reduction of pyruvate to lactate: elevated plasma concentrations of lactate - lactic acidosis

Answer 42

occurs during conditions of decreased organ perfusion (shock, MI) resulting in lactic acid failure of oxygen delivery to the tissues results in impaired oxidative phosphorylationand ATP synthesis. to survive, the cells rely on anaerobic glycolysis for generating tap, producing lactic acid as end product

Question 43

energy yield from glycolysis: anaerobic vs aerobic: direct product

Answer 43

an: 2 atp a: 2 nadh + h+ 2 ATP

Question 44

energy yield from glycolysis: anaerobic vs aerobic: final atp

Answer 44

an: 2 atp a: 4 or 6 atp. the number depends on which shuttle system transfers reducing equivalents to the etc. 4 bc 2 nadh.

Question 45

energy yield from glycolysis: anaerobic vs aerobic: total atp

Answer 45

an: 2 a: 6 or 8

Question 46

hormonal regulation of glycolysis: carried out by alloesteric activation or inhibition of covalent phosphorylation/dephosphorylation of rate limiting enzymes

Answer 46

short term regulation of glycolysis

Question 47

hormonal regulation of glycolysis: insulin and glucagon

Answer 47

more profound hormonal effects both are superimposed on the short term regulation. these effects can bring about 10-20 fold increases in enzyme activity typically occurring over hours to days. when plasma glucagon level is high and insulin is low (seen during fasting) or when plasma glucagon level is high and insulin is low as seen during uncontrolled diabetes. synthesis of glucokinase, phosphofructokinase and pk is decreased.

Question 48

effects of insulin on synthesis of key enzymes in liver: glucokinase, pfk1, and pyruvate kinasee

Answer 48

all +

Question 49

effects of glucagon on synthesis of key enzymes in liver: glucokinase, pfk1, and pyruvate kinase

Answer 49

all -

Question 50

alternate fate of pyruvate: oxidative decarboxylation of pyruvate by pyruvate dehydrogenase complex (PDH)

Answer 50

pyruvate dehydrogenase irreversibly converts pyruvate, the end product of glycolysis into acetyl cow, a major fuel for the tea cycle and the principal substrate for fatty acid synthesis

Question 51

alternate fate of pyruvate: this biotin dependent rxn is considered anapldrotic bc it replenishes the tca cycle intermediates and provides substrate for gluconeogenesis

Answer 51

carboxylation of pyruvate to oxaloacetate by pyruvate carboxylase

Question 52

alternate fate of pyruvate: the enzyme involved is alanine aminotransferase which requires pyrodizal phosphate as coenzyme

Answer 52

conversion of pyruvate to alanine via transamination

Question 53

what is the citric acid cycle or krebs

Answer 53

final common pathway for the oxidation of the major macromolecules, carbs, fats and proteins their metal results in the formation of acetyl cow or other intermediates of the cycle

Question 54

citric acid cycle - oxidative decarboxylation of pyruvate: by pdh (supplies substrate for cycle but not really part of tea cycle):

Answer 54

irreversibly converts pyruvate, the end product of glycolysis, into acetyl cow, a major fuel for the tea cycle and the principal substrate for fatty acid

Question 55

3 components enzymes of the pdh complex:

Answer 55

pyruvate decarboxylase, dihydrolipoyl transacetylase, dihydrolipoyl dehydrogenase. in addition two tightly bound regulatory enzymes: pdh kinase and pdh phosphatase