Glycolysis Flashcards

1
Q

What is the definition of glycolysis?

A

Glycolysis is a catabolic pathway in which one molecule of glucose is converted into two molecules of pyruvate. This process generates ATP directly and NADH from the oxidation of metabolites

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2
Q

Where do the reactions of glycolysis take place?

A

All 10 enzyme-catalyzed reactions of glycolysis occur in the cytosol

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3
Q

What are the two stages of glycolysis?

A

○ Stage 1: Energy Investment - In this stage, glucose is activated, energy (ATP) is consumed, and reactions involve “hexose” (6 carbon) sugars.
○ Stage 2: Energy Payout - In this stage, energy is harvested in the form of ATP, NADH is also generated, and reactions involve “triose” (3 carbon) sugars.

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4
Q

How many ATP molecules are consumed in the energy investment phase of glycolysis, per glucose molecule?

A

Two ATP molecules are consumed for every glucose molecule in the energy investment phase of glycolysis.

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5
Q

How many ATP molecules are generated in the energy payout phase of glycolysis, per glucose molecule?

A

Four ATP molecules are generated for every glucose molecule in the energy payout phase of glycolysis.

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6
Q

What is the net yield of ATP molecules produced per glucose molecule, after glycolysis is complete?

A

The net yield of ATP from glycolysis is 2 ATP molecules per glucose molecule. This is because 2 ATP are invested in stage 1 and 4 ATP are generated in stage 2

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7
Q

List three characteristics of the reaction catalyzed by hexokinase.

A

The reaction catalyzed by hexokinase is irreversible, exergonic, and has a ΔG &laquo_space;0. It is a coupled reaction in which ATP is used, and is a phosphate transfer reaction.

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8
Q

What type of reaction is the conversion of glucose to glucose-6-phosphate?

A

This reaction is a phosphorylation reaction in which ATP is the phosphate donor.

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9
Q

Is the reaction catalyzed by hexokinase regulated?

A

Yes, the reaction catalyzed by hexokinase is regulated, but it is not the rate limiting step of glycolysis.

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10
Q

What is the difference between an aldose and a ketose?

A

An aldose is a sugar containing an aldehyde group, while a ketose is a sugar containing a ketone group

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11
Q

Provide three descriptors for glucose

A

Glucose is an aldose, a hexose, and an aldohexose, meaning that it is a 6-carbon sugar containing an aldehyde group

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12
Q

What type of reaction is the conversion of glucose-6-phosphate (G6P) to fructose-6-phosphate (F6P)?

A

The conversion of G6P to F6P is an isomerization reaction in which an aldehyde group is converted to a ketone group. It is a reversible reaction with a ΔG of approximately zero

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13
Q

List three characteristics of the reaction catalyzed by phosphofructokinase-1 (PFK-1)

A

The reaction catalyzed by PFK-1 is irreversible, exergonic, and has a ΔG &laquo_space;0. It is a coupled reaction in which ATP is used, and it is a phosphate transfer reaction

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14
Q

Is the reaction catalyzed by PFK-1 regulated?

A

Yes, the reaction catalyzed by PFK-1 is regulated, and it is the rate limiting step of glycolysis.

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15
Q

What type of reaction is the conversion of fructose-6-phosphate (F6P) to fructose-1,6-bisphosphate (F-1,6-BP)?

A

This reaction is a phosphorylation reaction in which ATP is the phosphate donor

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16
Q

What happens during the lysis step of glycolysis?

A

During the lysis step of glycolysis, fructose-1,6-bisphosphate (F-1,6-BP) is cleaved into two 3-carbon molecules: dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP). This is a reversible reaction with a ΔG near zero. DHAP and GAP are isomers of each other.

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17
Q

What is the importance of the isomerization reaction that converts DHAP to GAP?

A

The isomerization of DHAP to GAP ensures that both products of the lysis reaction can continue through the glycolytic pathway. Although the lysis reaction produces two triose phosphates, only GAP can proceed directly through glycolysis. The isomerization of DHAP to GAP allows for the production of two molecules of GAP from one molecule of glucose.

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18
Q

Why do all reactions from GAP to pyruvate happen twice per glucose molecule?

A

All reactions from GAP to pyruvate happen twice per glucose molecule because one glucose molecule is broken down into two molecules of GAP.

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19
Q

What type of reaction is the conversion of glyceraldehyde-3-phosphate (GAP) to 1,3-bisphosphoglycerate (1,3-BPG)?

A

The conversion of GAP to 1,3-BPG is an oxidation reaction in which GAP is oxidized, and NAD+ is reduced to NADH. This is a reversible reaction with a ΔG of approximately zero. Inorganic phosphate is incorporated into 1,3-BPG, and it is considered an “energy capture” step.

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20
Q

Why is 1,3-BPG a “high-energy” intermediate?

A

1,3-BPG is a “high-energy” intermediate because it contains an acyl phosphate, which is a phosphate group attached to a carboxylate. This chemical group has a large, negative ΔG of hydrolysis, making it a good phosphate donor.

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21
Q

List four characteristics of the reaction that produces ATP from 1,3-BPG.

A

The reaction that produces ATP from 1,3-BPG is a coupled reaction, a phosphate-transfer reaction, a substrate-level phosphorylation reaction, and a reversible reaction with a ΔG of approximately zero. It is considered an “energy capture” step, and one ATP is produced per 1,3-BPG molecule, resulting in two ATP produced per glucose molecule

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22
Q

What type of reaction is the conversion of 3-phosphoglycerate to 2-phosphoglycerate?

A

The conversion of 3-phosphoglycerate to 2-phosphoglycerate is an isomerization reaction and a reversible reaction with a ΔG of approximately zero.

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23
Q

What type of reaction is the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PEP)?

A

The conversion of 2-phosphoglycerate to PEP is a dehydration reaction. It is a reversible reaction with a ΔG of approximately zero.

24
Q

Why is PEP considered a high-energy intermediate?

A

PEP is considered a high-energy intermediate because it has a large negative free energy of hydrolysis. This is due to the phosphate group being attached to an enol, which is unstable and readily tautomerizes to a ketone.

25
Q

List five characteristics of the reaction catalyzed by pyruvate kinase.

A

The reaction catalyzed by pyruvate kinase:
○ has a large amount of free energy released during the conversion of enolpyruvate to pyruvate.
○ has a ΔG &laquo_space;0 and is irreversible
○ is coupled to ATP synthesis
○ is a substrate-level phosphorylation reaction (phosphate transfer)
○ is an energy capture step in which 2 ATP are made per glucose

26
Q

Besides catalyzing a reaction in glycolysis, pyruvate kinase is also part of what type of regulation?

A

Pyruvate kinase is part of reciprocal regulation between glycolysis and gluconeogenesis

27
Q

Which three enzymes in glycolysis are regulated?

A

The three regulated enzymes in glycolysis are:
○ Hexokinase
○ Phosphofructokinase-1 (PFK-1)
○ Pyruvate kinase

28
Q

What are the four major mechanisms by which the rate of flux through metabolic pathways is regulated?

A

The four major mechanisms by which the rate of flux through metabolic pathways is regulated are:
○ Substrate availability
○ Alteration of enzyme activity
○ Alteration of amount of enzyme
○ Compartmentation

29
Q

List two mechanisms by which glycolysis is specifically regulated

A

Glycolysis is regulated by:
○ substrate availability, specifically glucose import via transporters.
○ enzyme regulation, specifically the regulation of hexokinase, phosphofructokinase-1, and pyruvate kinase.

30
Q

How is hexokinase regulated?

A

Hexokinase is inhibited by its product, glucose-6-phosphate (G6P), in a process called product inhibition. G6P acts as a negative allosteric effector.

31
Q

What is an allosteric enzyme?

A

An allosteric enzyme is an enzyme that changes its conformation and activity upon binding of an effector molecule at a site other than the active site. Effector molecules can be activators or inhibitors.

32
Q

How is PFK-1 regulated?

A

PFK-1 is allosterically regulated by several molecules:
○ ADP/AMP are allosteric activators of PFK-1, reflecting the cell’s need for ATP.
○ PEP is an allosteric inhibitor of PFK-1, signaling that the products of glycolysis are not being consumed.

33
Q

How is pyruvate kinase regulated?

A

Pyruvate kinase is an allosteric enzyme regulated by:
○ ATP, which is an allosteric inhibitor (product inhibition)
○ fructose-1,6-bisphosphate, which is a heteroallosteric activator (feedforward activation)

34
Q

Which steps in glycolysis are irreversible?

A

The irreversible steps in glycolysis are:
○ Step 1: glucose + ATP → glucose-6-phosphate + ADP + H+ (catalyzed by hexokinase)
○ Step 3: F-6-P + ATP → fructose-1,6-bisphosphate + ADP+ H+ (catalyzed by PFK-1)
○ Step 10: PEP + ADP + H+ → pyruvate + ATP (catalyzed by pyruvate kinase)

35
Q

How does the regulation of irreversible steps in glycolysis help maintain a steady state?

A

The synchronous regulation of irreversible reactions, along with the reversible nature of most enzyme-catalyzed reactions, helps to maintain a steady state for intermediates in glycolysis. This ensures that the pathway can proceed efficiently and that intermediates are available for other metabolic processes.

36
Q

What is glycogen?

A

Glycogen is a branched polymer of glucose that serves as a storage form of glucose in animals

37
Q

How does the breakdown of glycogen affect the net yield of ATP from glycolysis?

A

The breakdown of glycogen increases the net yield of ATP from glycolysis by one ATP per glucose unit. This is because the breakdown of glycogen produces glucose-1-phosphate, which can be converted to glucose-6-phosphate without the use of ATP. In contrast, the phosphorylation of glucose to glucose-6-phosphate in the first step of glycolysis requires ATP

38
Q

What are the possible fates of pyruvate?

A

○ Under anaerobic conditions:
■ Pyruvate can be reduced to lactate, regenerating NAD+ for glycolysis. This occurs in rapidly contracting muscle and erythrocytes.
■ Pyruvate can be converted to ethanol and CO2, regenerating NAD+ for glycolysis. This occurs in yeast.
○ Under aerobic conditions:
■ Pyruvate can be converted to acetyl-CoA, which enters the citric acid cycle. This is the main fate of pyruvate in most cells.

39
Q

Why is an anaerobic fate for pyruvate required?

A

An anaerobic fate for pyruvate is required to regenerate NAD+ for the continued oxidation of glyceraldehyde-3-phosphate in glycolysis under anaerobic conditions

40
Q

What is the myth of lactic acid?

A

The myth is that lactate build-up causes muscle soreness. However, lactate itself is not an acid. Muscle soreness is actually caused by microscopic tears in the muscle fibers. The hydrolysis of ATP by myosin during muscle contraction generates H+ that can cause acidotic damage. The conversion of pyruvate to lactate actually consumes H+, and export of lactate out of the cell can help prevent acidotic damage.

41
Q

What is the function of lactate dehydrogenase (LDH)?

A

LDH catalyzes the interconversion of pyruvate and lactate, using NADH as a cofactor.

42
Q

What is the aerobic fate of pyruvate?

A

The aerobic fate of pyruvate is conversion to acetyl-CoA via the pyruvate dehydrogenase reaction. Acetyl-CoA then enters the citric acid cycle.

43
Q

Where does the conversion of pyruvate to acetyl-CoA occur?

A

This conversion occurs inside mitochondria, in the matrix.

44
Q

How does pyruvate get from the cytosol to the mitochondrial matrix?

A

Pyruvate is transported across the inner mitochondrial membrane by the transporter protein, pyruvate translocase. This is a symporter that also transports a proton with the pyruvate.

45
Q

What is the functional portion of Coenzyme A, and how does it interact with acetyl groups?

A

The functional portion of Coenzyme A is the terminal sulfhydryl group, which forms a thioester bond with acetyl (and other acyl) groups.

46
Q

Why is the formation of acetyl-CoA a key irreversible step in carbohydrate metabolism?

A

The formation of acetyl-CoA is irreversible and commits the pyruvate to either oxidation in the citric acid cycle or fatty acid synthesis. Acetyl-CoA cannot be used to make glucose in mammals.

47
Q

List three descriptors for the pyruvate dehydrogenase reaction.

A

The pyruvate dehydrogenase reaction:
○ is an oxidative decarboxylation.
○ involves a transacetylation.
○ is irreversible.

48
Q

What is the pyruvate dehydrogenase complex (PDH)?

A

The PDH is a multienzyme complex that catalyzes the conversion of pyruvate to acetyl-CoA. It contains multiple copies of three catalytic enzymes and requires 5 cofactors, including NAD+, FAD, and CoA. It is also regulated by kinases and phosphatases.

49
Q

What are the advantages of multienzyme complexes?

A

Multienzyme complexes offer several advantages:
○ They speed up reaction times by bringing the enzymes and substrates into close proximity.
○ They limit the number of side reactions by channeling intermediates directly between enzymes.
○ The enzymes within the complex can be controlled as a single unit.

50
Q

List four factors that regulate the pyruvate dehydrogenase complex.

A

The pyruvate dehydrogenase complex is regulated by:
○ NAD+/NADH ratio
○ Acetyl-CoA concentration
○ Ca++ concentration
○ Reversible phosphorylation

51
Q

What is the effect of NADH on PDH activity?

A

NADH inhibits PDH activity. This is an example of allosteric regulation, as NADH is a product of the PDH reaction.

52
Q

How does phosphorylation affect PDH activity?

A

Phosphorylation of PDH by a kinase switches off the activity of the complex, while dephosphorylation by a phosphatase activates the complex. PDH is switched off when energy levels are high.

53
Q

What is the effect of Ca++ on PDH activity?

A

Ca++ activates PDH activity by activating a phosphatase that dephosphorylates PDH.

54
Q

What is the effect of acetyl-CoA on PDH activity?

A

Acetyl-CoA inhibits PDH activity. This is another example of allosteric regulation, as acetyl-CoA is a product of the PDH reaction.

55
Q

Which molecules activate the PDH complex, and which molecules inhibit it?

A

○ NAD+ and HS-CoA activate the PDH complex.
○ NADH and acetyl-CoA inhibit the PDH complex.