Glycolysis Flashcards

1
Q

What is the molecule that forms the starting point for glycolysis?

A

glucose

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2
Q

What molecule is produced from the first step in stage 1 of glycolysis?

A

glucose 6-phosphate

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3
Q

What are the two main purposes of the production of glucose 6-phosphate from glucose during the first step of glycolysis?

A
  1. glucose 6-phosphate cannot pass through the cell membrane so is trapped in the cell
  2. the phosphory group addition destabilises glucose, facilitating its further metabolism
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4
Q

What enzyme catalyses the conversion of glucose to glucose 6-phosphate during the first step of glycolysis?

A

hexokinase

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5
Q

What molecule is produced from glucose 6-phosphate during the second step os stage 1 of glycolysis?

A

fructose 6-phosphate

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6
Q

What is the importance of the conversion of glucose 6-phosphate into fructose 6-phosphate for the later stages of glycolysis?

A

Unlike glucose 6-phosphate, fructose 6-phosphate is readily split into two three-carbon fragments. This is important as in the later stages of glycolysis only three-carbon molecules are metabolised.

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7
Q

What enzyme catalyses the conversion of glucose 6-phosephate to fructose 6-phosphate during the second step of glycolysis?

A

phosphoglucose isomerase

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8
Q

What is produced from fructose 6-phosphate during the third step of stage 1 of glycolysis?

A

fructose 1,6-bisphosphate

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9
Q

What enzyme catalyses the conversion of fructose 6-phosphate to fructose 1,6-bisphosphate during the third step of stage 1 of glycolysis?

A

phosphofructokinase

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10
Q

What is the key regulatory step that sets the pace in glygolysis? What enzyme is involved? What are two reasons that this step is important?

A

Phosphofructokinase (PFK) catalyses the phosphorylation of fructose 6-phosphate by ATP to fructose 1,6-bisphosphate.

  1. stabilizes the fructose isomer
  2. prepares the way for the generation of two phosphorylated three-carbon fragments (the actual substrates for the ATP-generation phase of glycolysis)
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11
Q

In the second stage of glycolysis, fructose 1,6-bisphosphate is split into two triose phosphates. What are their names and which of them is on the direct pathway of glycolysis?

A
  • glyceraldehyde 3-phosphate (GAP)
  • dihydroxyacetone phosphate (DHAP)

Glyceraldahyde 3-phosphate is on the direct pathway of glycolysis.

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12
Q

What enzyme catalyses the cleaving of fructose 1,6-bisphosphate into two three-carbon units during the second stage of glycolysis?

A

aldolase

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13
Q

Only glyceraldehyde 3-phosphate is on the direct pathway of glycolysis. What is the enzyme that catylyses the interconversion between dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP)?

Why is this interconversion important?

A
  • triose phosphate isomerase
  • so that the three-carbon fragment that would be lost if dihydroxyacetone remained in this form, unusable, is not wasted
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14
Q

How many molecules of ATP are invested in stage 1 of glycolysis?

How many are generated during the final stage 3?

Net ATP yield per glucose?

A

2 are invested initially.

Stage 3 runs through twice so 4 are generated.

Net yield = 2

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15
Q

What product is generated from glyceraldehyde 3-phosphate after the first step of stage 3 of glycolysis?

A

1,3-bisphosphaglycerate

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16
Q

What enzyme catalyses the conversion of glyceraldehyde 3-phosphate into 1,3-bisphosphoglycerate in the first step of stage 3 of gluconeogenesis?

A

glyceraldehyde 3-phosphate dehydrogenase

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17
Q

What makes 1,3-bisphosphoglygerate so important during this stage of glycolosis?

A

Energy-rich molecule with greater phosphorylation potential than ATP - can be used for ATP synthesis.

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18
Q

What is the term used to describe the process of ATP synthesis from ADP and orthophosphate?

A

Substrate-level phosphorylation.

This occurs when ATP or GTP is generated by the transfer of a phosphate group from a substrate directly to ADP or GDP. Transferring from a higher energy (whether phosphate group attached or not) into a lower energy product (*wiki)

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19
Q

Why is substrate level phosphorylation called this?

A

Because the phosphate donor, 1,3-bisphosphoglycerate is a kinase substrate with high phosphoryl-transfer potential

20
Q

What product is produced (and enters the next step) during the third stage of glycolysis when 1,3-bisphosphoglycerate synthesises ATP from ADP and orthophosphate?

A

3-phosphoglycerate

21
Q

What enzyme catalyses the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate during the third stage of glycolysis?

A

Phosphoglycerate kinase

22
Q

In summary, what has occured during stage 3 of glycolysis leading up to the production of 3-phosphoglycerate?

A

“In essence, the energy released in the oxidation of glyceraldehyde 3-phosphate to 3-phosphoglycerate is temporarily trapped as 1,3-bisphosphoglycerate. This energy powers the transfer of a phosphoryl group from 1,3 bisphosphoglycerate to ADP to yield ATP.”

(Biochemistry: A Short Course, p.232)

23
Q

What product is produced from 3-phosphoglycerate in stage 3 of glycolysis?

A

2-phoshoglycerate

24
Q

What enzyme catalyses the conversion of 3-phosphoglycerate to 2-phosphoglycerate during stage three of glycolysis?

A

phosphoglycerate mutase

25
Q

What product is produced during glycolysis stage 3 from 2-phosphoglycerate?

A

Phosphenolpyruvate

26
Q

What enzyme catalyses the production of phosphoelolpyruvate from 2-phosphoglycerate during stage 3 of glycolysis?

A

enolase

27
Q

Enolase catalyzes the formation of the enol phosphate phosphoenolpyruvate (PEP) from 2-phosphoglycerate. This dehydration markedly elevates the transfer potential of the phosphoryl group.

Why does phosphoenolpyruvate have such a high phosphoryl-transfer potential?

A

“The phosphoryl group traps the molecule in its unstable enol form.When the phosphoryl group has been donated to ATP, the enol is able to undergo a conversion into the more stable ketone—namely, pyruvate.”

(B:ASC p 233)

28
Q

What final product of glycolysis is produced from phosphoenolpyruvate?

A

pyruvate

29
Q

What is concomitantly generated during the conversion of phosphoenolpyruvate to pyruvate?

A

ATP

30
Q

What enzyme catalyses the final step in glycolysis that produces pyruvate?

A

pyruvate kinase

31
Q

Why is the further metabolism of pyruvate needed after glycolysis has produced this molecule (two reasons)?

A
  1. to maintain redox balance - in the process of glycolysis, the activity of glyceraldehyde 3-phosphate dehydrogenase leads to the reduction of NAD+ to NADH when glyceraldehyde 3-phosphate is oxidized. NAD+ is limited in the cell, so must be regenerated for glycolysis to proceed
  2. Further energy extraction - anaerobic metabolism or production of Acetyl CoA that can enter oxidative metabolic pathways
32
Q

What are the three possible metabolic fates of pyruvate after glycolysis? Which of these are aerobic and which are anaerobic?

A
  1. (anaerobic) conversion into ethanol (alcoholic fermentation: yeast and other microorganisms)
  2. (anaerobic) conversion into lactate (lactic acid fermentation: variety of microorganisms, and other animals when oxygen is limited)
  3. (aerobic) conversion into carbon dioxide and water through the citric acid cycle and the electron transport chain
33
Q

How is NAD+ regenerated in alcoholic fermentation?

A

Pyruvate is first decarboxylated (enzyme: pyruvate decarboxylase; coenzyme: thiamine pyrophosphate, from vit B1) into acetaldehyde. This is then reduced to ethanol by NADH in a reaction catalysed by alcohol dehydrogenase. This is the reaction that regenerates NAD+.

34
Q

How does lactic acid fermentation regenerate NAD+? Why is this limited in animals?

A

Pyruvate accepts electrons from NADH to form lactate in a reaction catalysed by lactate dehydrogenase. This regenerates NADH to NAD+ under anaerobic conditions.

However, it also produces lactate (lactic acid) build-up, excess of which can be a problem for skeletal muscles, causing fatigue and a burning sensation.

35
Q
A
36
Q

Far more energy can be released from glucose under aerobic conditions. What is the molecule formed from pyruvate that that becomes the point of entry into oxidative metaboic pathways and how is it formed from pyruvate inside mitochondria?

A

Acetyl CoA.

Pyruvate + NAD+ + CoA –> acetyl CoA + CO2 + NADH

In this pathway, the NAD+ used earlier and in this reaction is regenerated in the electron transport chain.

37
Q

What are the two main roles of glycolysis?

A
  1. degrades glucose to generate ATP
  2. provides building blocks for synthetic reactions (e.g. formation of fatty acids and amino acids)
38
Q

What enzymes catalyse which three essentially irreversible steps in glycolysis, thereby forming the primary sites for regulation of glycolysis?

A
  1. hexokinase: stage 1: the phosphorylation of glucose by ATP to form glucose 6-phosphate
  2. phosphofuctokinase: stage 1: the phosphorylation by ATP of fructose 6-phosphate to fructose 1,6-bisphosphate
  3. pyruvate kinase: stage 3: the transfer of a phosphoryl group from the unstable enol phosphoenolpyruvate to ADP to produce ATP and the more stable ketone, pyruvate
39
Q

What is the “committed step” of glycolysis?

A

The phosphorylation of fructose 6-
phosphate to fructose 1,6-bisphosphate by PFK

40
Q

Phosphofructokinase is the most important control site in the mammalian glycolytic pathway. As glycolysis is active when the body needs to generate ATP, when there is plenty of ATP around, glycolysis can be inhibited. How is phosphofructokinase regulation achieved by this at the muscle tissue?

A
  • High levels of ATP allosterically inhibit the phosphofructokinase enzyme.
  • The binding of ATP to the regulatory site lowers the enzyme’s affinity for fructose 6-phosphate, inhibiting the progression of glycolysis
41
Q

When ATP levels are low, phosphofructokinase activity at the muscle needs to be higher so that glycolysis can proceed. How does the altered ATP:AMP ratio achieve this?

A
  • When ATP is low and has been dephosphorylated twice to AMP, the AMP outcompetes ATP for the same allosteric site on phosphofrutcokinase because there is more of it around.
  • However, when AMP binds to the site, it does NOT inhibit phosphofrutcokinase activity
  • As such, phosphofrutcokinase activity increases in the presence of high quantities of AMP over ATP (so when more glucose needs to be metabolised for energy)
42
Q

What does the effect of lower pH (higher acidity) have on phosphofructokinase activity at the muscle? What is the purpose of this?

A
  • Lower pH inhibits phosphofructokinase activity by augmenting the inhibitory effect of ATP
  • When metabolism at the muscle is working anaerobially (such as during extreme exercise) it will produce excessive lactic acid from pyruvate after glycolysis, which can damage the muscle. The inhibition of glycolysis reduces pyruvate production and therefor reduces lactic acid production, protecting the muscle.
43
Q

What is hexokinase inhibited by and why?

A
  • Hexokinase is the enzyme catalysing the first step of glycolysis. It is inhibited by its product, glucose 6-phosphate.
  • This signals that no more glucose needs to be broken down
  • When PFK is inactive, fructose 6-phosphate rises and therefore so does glucose 6-phosphate which it is in equilibium with. The inhibition of phosphofructokinase therefore leads to the inhibition of hexokinase
44
Q

What (list two molecules) inhibits pyruvate kinase in the third stage of glycolysis at the muscle tissue?

A
  1. ATP, when the engery charge of the cell is high.
  2. Alanine - this is synthesised in one step from pyruvate ad signals that building blocks, for things like muscle protein, are abundant.
45
Q

How does the regulation of phosphofructokinase differ in the liver from in the muscle?

A
  • The regulation by the ATP:AMP ratio is not as important because ATP levels in the liver don’t fluctuate like they do in the muscles
  • Lactate is not usually produced in the liver (in fact it is converted to glucose there) so low pH is not a metabolic signal there in the same way
  • PFK here inhibited by citrate (early intermediate in TCA cycle) as this means biosynthetic precursors are abundant so no need to degrade additional glucose
  • fructose 2,6-bisphosphate (F-2,6-BP) is stimulated by fructose 6-phosphate an activator of phosphofructokinase - stimulates glycolysis by increasing phosphofructokinase’s affinity for fructose 6-phosphate and diminishing the inhibitory effect of ATP (feedforward stimulation)
46
Q

How does the regulation of glycolysis by hexokinase differ in the liver from in the muscle?

A
  • The hexokinase reaction in the liver is controlled as in the muscle
  • However, glucose phorylation in the liver is largely done by glucokinase (hexokinase B)
  • This phosphorylates glucose only when glucose is abundant (like after a large meal) and has a fifty-fold lower affinity for glucose than does hexokinase so it only uses up the excess. This means the muscles and brain first call on glucose but ensures in the liver that excess is not wasted.
  • Glucokinase is not inhibited by its product, glucose 6-phosphate, as hexokinase
    is
  • role of glucokinase is to synthesise glycogen & fatty acids
47
Q

How does regulation of the liver (L) form of pyruvate kinase differ from regulation of the muscle (M) form?

A
  • The catalytic properties of the L form—but not of the M form are controlled by reversible phosphorylation
  • “When the blood-glucose level is low, the glucagon-triggered cyclic AMP cascade leads to the phosphorylation of pyruvate kinase, which diminishes its activity. This hormone-triggered phosphorylation prevents the liver from consuming glucose when it is more urgently needed by brain and muscle” (p. 244)