Chapter 15: Glycolysis

Question 1

Other name for glycolysis?

Answer 1

“Embden-Meyerhof pathway”

“Embden-Meyerhof-Parnas pathway”

Question 2

Overview of Glycolysis?

Answer 2

is a sequence of 10 enzymatic reactions in which one molecule of glucose is converted to two molecules of the three-carbon compound pyruvate with the concomitant generation of 2 ATP. and the reduction of 2 NAD +to 2 NADH.

It plays a key role in energy metabolism by providing a significant portion of the free energy used by most organisms and by preparing glucose and other compounds for further oxidative degradation.
Glycolysis involves the breakdown of glucose to pyruvate while using the free energy released in the process to synthesize ATP from ADP and Pi .

• The 10-reaction sequence of glycolysis is divided into two stages: energy investment and energy recovery.

Question 3

What happens during the two phases of glycolysis?

Answer 3

Stage I

Energy investment (Reactions 1–5). In this preparatory stage, the hexose glucose is phosphorylated and cleaved to yield two molecules of the triose glyceraldehyde-3-phosphate. This process consumes 2 ATP. Stage II Energy recovery (Reactions 6–10). The two molecules of glyceraldehyde-3-phosphate are converted to pyruvate, with concomitant generation of 4 ATP. Glycolysis therefore has a net “profit” of 2 ATP per glucose: Stage I consumes 2 ATP; Stage II produces 4 ATP.

Question 4

How many ATP are invested and how many are recovered from each molecule of glucose that follows the glycolytic pathway?

Answer 4

Stage I invests 2 ATP; Stage II produces 4 ATP.

Question 5

Compare the oxidation states of glucose and pyruvate. Explain why glycolysis generates NADH.

Answer 5

Glycolysis has a lower oxidation state than pyruvate and pyruvate has a higher oxidation state
Some of the glycolytic steps involves a redox reaction in which so NAD+ is reduced. the NADH formed in the process must be continually reoxidized to keep the pathway supplied with its primary oxidizing agent, NAD+

Question 6

What is the first reaction?

Answer 6

Reaction 1 of glycolysis is the transfer of a phosphoryl group from ATP to glucose to form glucose-6-phosphate (G6P) in a reaction catalyzed by hexokinase.
Hexokinase Uses the First ATP

Question 7

What is a kinase? What is indicated by the prefix of the kinase name? What does Hexokinase catalyze based on its prefix?

Answer 7

A kinase is an enzyme that transfers phosphoryl groups between ATP and a metabolite. The metabolite that serves as the phosphoryl group acceptor is indicated in the prefix of the kinase name.

catalyzes the phosphorylation of hexoses such as D-glucose, D-mannose, and D-fructose.

Question 8

Liver cells contain what kinase? Difference between it and hexokinase?

Answer 8

Liver cells also contain the isozyme glucokinase, which catalyzes the same reaction but which is primarily involved in maintaining blood glucose levels

Hexokinase has a high affinity for glucose and is inhibited by G6P

Glucokinase has a low affinity for glucose and is not inhibited by G6P

Question 9

The second substrate for hexokinase, as for other kinases, is an? Function?

Answer 9

Mg2+–ATP complex.

Question 10

What is Reaction 2?

Answer 10

Reaction 2 of glycolysis is the conversion of G6P to fructose-6-phosphate (F6P) isomerize phosphoglucose isomerase (PGI).
This is the isomerization of an aldose to a ketose.

Phosphoglucose Isomerase Converts Glucose-6-Phosphate to Fructose-6-Phosphate

Question 11

How does reaction 2 occur?

Answer 11

Since G6P and F6P both exist predominantly in their cyclic forms, the reaction requires ring opening followed by isomerization and subsequent ring closure

Question 12

What happens in Reaction 3?

Answer 12

Phosphofructokinase Uses the Second ATP

In Reaction 3 of glycolysis, phosphofructokinase (PFK) phosphorylates F6P to yield fructose-1,6-bisphosphate (FBP or F1,6P).
The PFK reaction is similar to the hexokinase reaction.

Question 13

Phosphofructokinase plays a central role in control of glycolysis because it ?

Answer 13

-catalyzes one of the pathway’s rate-determining steps

-plays major role in regulation of glycolysis

Question 14

Why is the product bisphosphate rather than a diphosphate?

Answer 14

The product is a bisphosphate rather than a diphosphate because its two phosphate groups are not attached directly to each other.)

Question 15

What is Reaction 4?

Answer 15

Aldolase Converts a 6-Carbon Compound to Two 3-Carbon Compounds
known as idol cleavage or retro idol condensation
Glucose is cleaved by aldolase to yield the trioses glyceraldehyde-3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP)

aldol cleavage of FBP results in two interconvertible C 3 compounds that can therefore enter a common degradative pathway.

Question 16

What is Reaction 5? What is the intermediate

Answer 16

Triose Phosphate Isomerase Interconverts Dihydroxyacetone Phosphate and Glyceraldehyde-3-Phosphate
They are interconverted by an isomerization reaction with an enediol (or enediolate) intermediate.

a process in which two things are each converted into the other

Question 17

Support for this reaction 5 scheme comes from the use of?

Answer 17

f the transition state analogs phosphoglycohydroxamate and 2-phosphoglycolate, stable compounds whose geometry resembles that of the proposed enediol or enediolate intermediate:
Enzymes catalyze reactions by binding the transition state complex more tightly than the substrate

Question 18

TIM was the first protein found to contain?

Answer 18

an α/ β barrel (also known as a TIM barrel), a cylinder of eight parallel β strands surrounded by eight parallel α helices

Question 19

Triose Phosphate Isomerase Achieved catalytic perfection. What does this mean?

Answer 19

By this it is meant that the rate of the bimolecular reaction between enzyme and substrate is diffusion controlled, so product formation occurs as rapidly as enzyme and substrate can collide in solution.

GAP and DHAP are interconverted so efficiently that the concentrations of the two metabolites are maintained at their equilibrium values

Question 20

Which one of the products (GAP or DHAP) of the aldol cleavage reaction continues along the glycolytic pathway

Answer 20

GAP is consumed in the succeeding reactions of the glycolytic pathway. As GAP is siphoned off in this manner, more DHAP is converted to GAP to maintain the equilibrium ratio. In effect, DHAP follows GAP into the second stage of glycolysis, so a single pathway accounts for the metabolism of both products of the aldolase reaction.

Question 21

Taking Stock of Glycolysis So Far

Answer 21

At this point in the glycolytic pathway, one molecule of glucose has been transformed into two molecules of GAP. This completes the first stage of glycolysis (Fig. 15-7). Note that 2 ATP have been consumed in generating the phosphorylated intermediates. This energy investment has not yet paid off, but with a little chemical artistry, the “low-energy” GAP can be converted to “high-energy” compounds whose free energies of hydrolysis can be coupled to ATP synthesis in the second stage of glycolysis.

Question 22

What is Reaction 6?

Answer 22

Glyceraldehyde-3-Phosphate Dehydrogenase Forms the First “High-Energy” Intermediate

Reaction 6 of glycolysis is the oxidation and phosphorylation of GAP by NAD+ and P i as catalyzed by glyceraldehyde-3-phosphate dehydrogenase (GAPDH; driving the synthesis of 1-3 BOG

GAP is oxidatively phosphorylated by glyceraldehyde-3-phosphate dehydrogenase (GAPDH)

For each glucose, 2 NADH are produced in Step 6.

Question 23

How is 1-3 BPG an acyl phosphate synthesized in Reaction 6?
2 ways

Answer 23

aldehyde oxidation drives its synthesis

A “high-energy” acyl phosphate (a mixed anhydride) is formed using Pi .
In this reaction, aldehyde oxidation, an exergonic reaction, drives the synthesis of the “highenergy” acyl phosphate 1,3-bisphosphoglycerate (1,3-BPG).
Recall that acyl phosphates are compounds with high phosphoryl group-transfer potential

Question 24

What is Reaction 7?

Answer 24

Phosphoglycerate Kinase Generates the First ATP also known as “substrate-level phosphorylation

aka dephosphorylated by phosphoglycerate kinase (PGK) to produce ATP

Reaction 7 of the glycolytic pathway yields ATP together with 3-phosphoglycerate (3PG) in a reaction catalyzed by phosphoglycerate kinase (PGK).

Question 25

Why does The phosphoglycerate kinase reaction “pulls” the glyceraldehyde-3-phosphate dehydrogenase reaction?

Answer 25

Because The GAPDH and PGK Reactions Are Coupled. As described in Section 14-2B, a slightly unfavorable reaction can be coupled to a highly favorable reaction so both reactions proceed in the forward direction. In the case of the sixth and seventh reactions of glycolysis, 1,3-BPG is the common intermediate whose consumption in the PGK reaction “pulls” the GAPDH reaction forward.

Question 26

Although the GAPDH reaction is endergonic, the strongly exergonic nature of the transfer of a phosphoryl group from 1,3-BPG to ADP makes the overall synthesis of NADH and ATP from GAP, Pi , NAD+ , and ADP favorable. This production of ATP, which does not involve O2, is an example of?

Answer 26

substrate-level phosphorylation.

Question 27

What is Reaction 8?

Answer 27

Phosphoglycerate Mutase Interconverts 3-Phosphoglycerate and 2-Phosphoglycerate

In Reaction 8 of glycolysis, 3PG is converted to 2-phosphoglycerate (2PG) by phosphoglycerate mutase (PGM):
isomerization

This more or less energetically neutral reaction is necessary preparation for the next reaction in glycolysis, which generates a “highenergy” phosphoryl compound.

Question 28

What is a mutate

Answer 28

catalyze the group transfer of a functional group from one position to another on a molecule

Question 29

2,3-BPG can dissociate, leaving the enzyme in an inactive (dephosphorylated) form. For reactivation, free 2,3-BPG must

Answer 29

be available.

Question 30

Whats is Reaction 9?

Answer 30

Enolase Forms the Second “High-Energy” Intermediate

In Reaction 9 of glycolysis, 2PG is dehydrated to phosphoenolpyruvate (PEP) in a reaction catalyzed by enolase

dehydrated by enolase

Question 31

What is Reaction 10?

Answer 31

Pyruvate Kinase Generates the Second ATP known as (substrate-level phosphorylation)

In Reaction 10 of glycolysis, its final reaction, pyruvate kinase (PK) couples the free energy of PEP cleavage to the synthesis of ATP during the formation of pyruvate:

dephosphorylated by pyruvate kinase to produce a second ATP and pyruvate.

Question 32

The PK reaction is highly exergonic, supplying more than enough free energy to drive ATP synthesis. The high phosphoryl group-transfer potential of PEP reflects the large release of free energy on converting the product enolpyruvate to its keto tautomer.Where does the energy go?Why such a “waste” of energy??

Answer 32

Where does the energy go? Heat

Why such a “waste” of energy? Drives reaction forward

Question 33

Assessing Stage II of Glycolysis.

Answer 33

This stage produces 4 ATP per glucose for a net yield of 2 ATP per glucose.

The energy investment of the first stage of glycolysis (2 ATP consumed) is doubly repaid in the second stage of glycolysis because two phosphorylated C 3 units are transformed to two pyruvates with the coupled synthesis of 4 ATP.

• 2 ATP/glucose obtained by substrate-level phosphorylation
• 2 NADH generated; under aerobic conditions, 2 electrons generated by re-oxidation of NADH are passed through the electron transport chain to O2 , which drives synthesis of more ATP.
• 2 pyruvate generated

Question 34

What happens to pyruvate (and NADH) under anaerobic conditions?

Answer 34

(A) Under anaerobic conditions in muscle, pyruvate is reduced to lactate to regenerate NAD + in a process known as homolactic fermentation (a fermentation is an anaerobic biological process).

(b) In yeast and certain other microorganisms, pyruvate is decarboxylated to yield CO 2 and acetaldehyde, which is then reduced by NADH to yield NAD + and ethanol. This process is known as alcoholic fermentation.

Question 35

Describe the three possible fates of pyruvate.

Answer 35

1. Under aerobic conditions, the pyruvate is completely oxidized via the citric acid cycle to CO 2 and H2 O.
2. Under anaerobic conditions, pyruvate must be converted to a reduced end product in order to reoxidize the NADH produced by the GAPDH reaction. This occurs in two ways:

(a) Under anaerobic conditions in muscle, pyruvate is reduced to lactate to regenerate NAD + in a process known as homolactic fermentation (a fermentation is an anaerobic biological process).

(b) In yeast and certain other microorganisms, pyruvate is decarboxylated to yield CO 2 and acetaldehyde, which is then reduced by NADH to yield NAD + and ethanol. This process is known as alcoholic fermentation.

Under aerobic conditions, the pyruvate carbons are oxidized to CO 2 by the citric acid cycle and the electrons are eventually transferred to O 2 to yield H2 O in oxidative phosphorylation.

Under anaerobic conditions in muscle, pyruvate is reversibly converted to lactate, whereas in yeast, it is converted to CO 2 and ethanol.

Question 36

How does NADH act in aerobic and anaerobic glycolysis

Answer 36

Thus, in aerobic glycolysis, NADH acts as a “high-energy” compound, whereas in anaerobic glycolysis, its free energy of oxidation is dissipated as heat.

Question 37

NADH, a substrate for the GAPDH reaction must be ____ for glycolysis to continue?

Answer 37

reoxidized

Question 38

What is homolactic fermentation?

Answer 38

The process in which Under anaerobic conditions in muscle, pyruvate is reduced to lactate to regenerate NAD +

Question 39

In muscle, during vigorous activity, when the demand for ATP is high and oxygen is in short supply, ATP is synthesized largely via ?, which rapidly generates ATP, rather than through the slower process of oxidative phosphorylation.
What

Answer 39

anaerobic glycolysis

Question 40

What catalyzes the oxidation of NADH by pyruvate to yield NAD+ and lactate.

Answer 40

lactate dehydrogenase (LDH)

This reaction is often classified as Reaction 11 of glycolysis. The lactate dehydrogenase reaction is freely reversible, so pyruvate and lactate concentrations are readily equilibrated.

Question 41

end result of lactate

Answer 41

Lactate represents a sort of dead end for anaerobic glucose metabolism. The lactate can be either exported from the cell or converted back to pyruvate. Much of the lactate produced in skeletal muscle cells is carried by the blood to the liver, where it is used to synthesize glucose

Question 42

What is Alcoholic Fermentation?

Answer 42

Alcoholic Fermentation Converts Pyruvate to Ethanol and CO2

In yeast and certain other microorganisms, pyruvate is decarboxylated to yield CO 2 and acetaldehyde, which is then reduced by NADH to yield NAD +and ethanol.

the conversion of pyruvate to ethanol and CO2. to regenerate NAD+ FOR glycolysis

Question 43

Yeast produces ethanol and CO 2 via what two consecutive reactions?

Answer 43

1. The decarboxylation of pyruvate to form acetaldehyde and CO 2 as catalyzed by pyruvate decarboxylase (an enzyme not present in animals).
2. The reduction of acetaldehyde to ethanol by NADH as catalyzed by alcohol dehydrogenase (Section 11-1C), thereby regenerating NAD + for use in the GAPDH reaction of glycolysis.

Question 44

which needs a cofactor, Alcoholic Fermentation or Homolactic Fermentation?

Answer 44

Alcoholic Fermentation,
TPP Is an Essential Cofactor of Pyruvate Decarboxylase. Pyruvate decarboxylase contains the coenzyme thiamine
pyrophosphate
pyruvate is decarboxylated by a thiamine pyrophosphate (TPP)–dependent mechanism, and the resulting acetaldehyde is reduced to ethanol.

Question 45

What is TPP synthesized from? Deficiency in it causes?

Answer 45

TPP, which is synthesized from thiamine (vitamin B1 ), binds tightly but noncovalently to pyruvate decarboxylase

Vitamin B 1 Deficiency Causes Beriberi and Wernicke-Korsakoff syndrome.

Question 46

Compare the ATP yields and rates of ATP production for anaerobic and aerobic degradation of glucose.

Answer 46

he rate of ATP production by anaerobic glycolysis can be up to 100 times faster than that of oxidative phosphorylation
But Aerobic yields more ATP 32 per glucose and Fermentation is 2 ATP per glucose
Consequently, when tissues such as muscle are rapidly consuming ATP, they regenerate it almost entirely by anaerobic glycolysis.

Question 47

What makes Enzymes candidates for flux-control points? Name three

Answer 47

Enzymes that function with large negative free energy changes.
hexokinase, phosphofructokinase, and pyruvate kinase

are metabolically irreversible.

Question 48

What is the primary flux control point for glycolysis and why?

Answer 48

Phosphofructokinase.

Because when the G6P source for glycolysis is glycogen, rather than glucose, as is often the case in skeletal muscle, the hexokinase reaction is not required.
Pyruvate kinase catalyzes the last reaction of glycolysis and is therefore unlikely to be the primary point for regulating flux through the entire pathway.
Evidently, PFK, an elaborately regulated enzyme functioning far from equilibrium, is the major control point for glycolysis in muscle under most conditions.

Question 49

Describe the mechanisms that control phosphofructokinase activity. (Inhibitors and Activators)

Answer 49

ATP is both a substrate and an allosteric inhibitor of phosphofructokinase. Other compounds, including ADP, AMP, and fructose-2,6-bisphosphate (F2,6P), reverse the inhibitory effects of ATP and are therefore activators of PFK

inhibited by ATP and activated by AMP and ADP.

Question 50

Describe the mechanisms that control phosphofructokinase, hexokinase, and pyruvate kinase activity. (Inhibitors and Activators)

Answer 50

ATP is both a substrate and an allosteric inhibitor of phosphofructokinase. Other compounds, including ADP, AMP, and fructose-2,6-bisphosphate (F2,6P), reverse the inhibitory effects of ATP and are therefore activators of PFK

inhibited by ATP and activated by AMP and ADP.

hexokinase is inhibited by G6P

pyruvate kinase activity is inhibited by ATP and activated by AMP, PEP

Question 51

describe structure of PFK

Answer 51

Each PFK subunit has two binding sites for ATP: a substrate site/catalytic site and an inhibitor/regulatory site site. The substrate site/catalytic site binds ATP equally well in either conformation, but the inhibitor site/regulatory site binds ATP almost exclusively in the T state. The other substrate of PFK, F6P, preferentially binds to the R state.

Question 52

At high concentrations of ATP, what happens to affinity for F6P?

Answer 52

ATP acts as an allosteric inhibitor of PFK by binding to the T state, thereby shifting the T ⇌ R equilibrium in favor of the T state and thus decreasing PFK’s affinity for F6P

In graphical terms, high concentrations of ATP shift the curve of PFK activity versus [F6P] to the right and make it even more sigmoidal (cooperative)

Question 53

AMP Overcomes the ATP Inhibition of PFK. How?

Answer 53

This results from AMP’s preferential binding to the R state of PFK

AMP binds preferentially to the regulatory site in the R-state.
Like ADP, AMP prevents R → T transition

Question 54

Why is ATP alone not an effective allosteric regulator of enzyme activity?

Answer 54

a little decrease in ATP concentration causes a huge rise in AMP levels,
As a result, AMP becomes the allosteric effector of this key regulating enzyme

Question 55

What besides PF accounts for flux control?

Answer 55

Substrate Cycling

effective means to create large changes in metabolic flux

Question 56

One reason why substrate cycling is important?

Answer 56

important for metabolic regulation and to generate heat in nonshivering thermogenesis, which can be stimulated by thyroid hormones.

Not futile

Question 57

Names of Metabolism of Hexoses Other than Glucose

Answer 57

The commonly available hexoses fructose, galactose, and mannose are converted to glycolytic intermediates for further metabolism.

fructose

In muscle:

mostly from saccharose (sucrose), a disaccharide of glucose and

hexokinase

Fru + ATP →

F6P + ADP

fructose

Question 58

What is the pentose phosphate pathway?
What two things do it generate?

Answer 58

generates nucleotides for DNA synthesis and generates NADPH for biosynthesis of fatty acids and cholesterol

• alternative pathway to glycolysis
• serves to generate NADPH