BB17 Glycolysis Flashcards

0
Q

Glycolysis is an

A

energy conservation pathway

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1
Q

Glycolysis

A
  • sequence of reactions that converts glucose into pyruvate

* relatively small amount of ATP produced

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2
Q

The chemical intermediates in glycolysis are either

A

six-carbon units
• derivatives of glucose or fructose

three-carbon units
• derivatives of glyceraldehydes, dihydroxyacetone, glycerate, pyruvate

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3
Q

All intermediates are phosphorylated with the phosphoryl groups linked as either

A

esters
anhydrides
••phosphorylation activates these intermediates

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4
Q

Stages of glycolysis

A

Stage 1 – trapping of glucose and its destabilization

Stage 2 – breakdown of a six-carbon unit to create 2 three-carbon units

Stage 3 – generates ATP

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5
Q

Stage 1

A

• traps glucose, forms a compound easily broken down into phosphorylated 3-C units

  1. add phosphate to trap and destabilize (glucose-6-phosphate)
  2. isomerization
    (fructose-6-phosphate)
  3. further phosphorylation (fructose-1,6-bisphosphate)
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6
Q

… adds phosphate to glucose to make glucose-6-phosphate

A

Hexokinase

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7
Q

Isomerization of
glucose-6-phosphate to
fructose-6-phosphate
catalyzed by

A
phosphoglucose isomerise
• opens 6-membered ring
• catalyzes the isomerisation
• promotes the formation of a 5-membered ring
* still 6 carbons – 1 is a side group
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8
Q

Second phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate catalyzed by

A

phosphofructokinase

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9
Q

Fructose-1,6-bisphosphate

A

molecule that’s easily cleaved into two 3-carbon units

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10
Q

Stage 2

A

produces two different 3-carbon units that are interconvertible

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11
Q

… cleaves
fructose-1,6-bisphosphate
into two 3-carbon units

A

aldolase

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12
Q

Fructose-1,6-bisphosphate is cleaved into

A
  • glyceraldehydes 3-phosphate (on glycolytic pathway)

* dihydroxyacetone phosphate (not on glycolytic pathway)

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13
Q

Glyceraldehyde 3-phosphate and dihydroxyacetone phosphate

A

• can be interconverted in an isomerisation process
• catalyzed by triose phosphate isomerise
(Tim-barrel)

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14
Q

Product of stage 2

A

2 x glyceraldehyde 3-phosphate

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15
Q

Stage 3

A

produces ATP
2x
4 ATP – 2ATP from stage 1
= 2 ATP gained

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16
Q

Stage 3

A
• 5 steps
1. glyaldehyde 3-phosphate
    =>1,3-bisphosphoglycerate 
     (1,3-BPG)
2. 1,3-BPG      
    =>  3-phosphoglycerate
3. 3-phosphoglycerate     
    => 2-phosphoglycerate
4. 2-phosphoglycerate      
    => phosphoenolpyruvate
5. phosphoenolpyruvate   
     =>   pyruvate   +   ATP

forms 2 ATP but repeated = 4 ATP

17
Q

Oxidation of glyceraldehyde 3-phosphate to

A

1,3-bisphosphoglycerate
• catalyzed by glyceraldehyde 3-phosphate dehydrogenase
• requires reduction of NAD+ to NADH

18
Q

1,3-BPG is a

A

high-potential phosphorylated product

• more energy released when losing phosphoryl group than in creating bond to make ATP from ADP

19
Q

A phosphoryl group is transferred from 1,3-BPG to ADP, forming

A

3-phosphoglycerate and ATP

• catalyzed by phosphoglycerate kinase

20
Q

A phosphoryl shift occurs in the conversion of 3-phosphoglycerate to

A

2-phosphoglycerate
• catalyzed by phosphoglycerate mutase
• 2-phosphoglycerate is less stable

21
Q

A dehydration converts

2-phosphoglycerate to

A

phosphoenolpyruvate
• catalyzed by enolase
• phosphoenolpyruvate is another high-potential phosphorylated compound

22
Q

A phosphoryl group is transferred from phosphoenolpyruvate to ADP, forming

A
pyruvate and ATP
• losing phosphoryl = pyruvate in unstable enol form
• rearranges to pyruvate
• catalyzed by pyruvate kinase
• virtually irreversible reaction
23
Q

The net reaction in the transformation of glucose into pyruvate is

A
• Glucose
• 2Pi
• 2 ADP
• 2 NAD+
=
• 2 Pyruvate
• 2 ATP
• 2 NADH
• 2H+
• 2 H2O
24
Q

One glucose molecule generates

A

2 molecules of ATP

2 molecules of pyruvate

25
Q

The reactions of glycolysis

A

(energetically favourable) are coupled to
the synthesis of ATP (energetically unfavourable)
via shared chemical intermediate

26
Q

There are 2 positions where ATP is formed

A

1) 1,3-Bisphosphoglycerate to 3-phosphoglycerate
• 1,3-BPG passes phosphate to ADP
= substrate level phosphorylation

2) the phosphoenolpyruvate to pyruvate
• loss of phosphate makes pyruvate in an unstable enol form
• free energy released on the arrangement of pyruvate into its more stable ketone form is more than is needed to produce ATP

27
Q

Glycolysis regulation reflects its dual role in

A
  • degrading glucose to make ATP

* providing building blocks for biosynthetic reactions (ie formation of long chain fatty acids)

28
Q

In metabolic pathways, enzymes catalyzing… are potential sites of control/regulation

A

essentially irreversible reactions

29
Q

Reactions catalyzed by…are virtually irreversible

A
  • Phosphofructokinase
  • Hexokinase
  • Pyruvate kinase
30
Q

Activities of control sites are regulated by

A
  • reversible allosteric control (ie feedback inhibition) – in milliseconds
  • reversible covalent modifaction (ie phosphorylation) – in seconds
  • transcriptional control – in hours
31
Q

The most important controlling element in the glycolytic pathway of mammals is

A

Phosphofructokinase

32
Q

2 features of the phosphofructokinase enzyme

A

1) regulation of ATP production

2) regulation to provision of building blocks

33
Q

Phosphofructokinase regulation of ATP production

A

• allosteric inhibition by high levels of ATP
• allosteric activation by high levels of AMP
(glycolysis is stimulated as the energy charge falls)
• to prevent excess formation of lactate the enzyme is also inhibited by H+ (low pH)

34
Q

Phosphofructokinase is stimulated by

A

fructose 2,6-bisphosphate

• a molecule produced only when glucose is abundant

35
Q

Phosphofructokinase regulation of provision of building blocks

A

the enzyme is inhibited by citrate, an early intermediate in the citric acid cycle

36
Q

Other enzymes that regulate glycolysis

A
  • hexokinase

* pyruvate kinase

37
Q

Hexokinase

A

inhibited by increased levels of glucose 6-phosphate
fructokinase 6-phosphate
• ie when phosphofructokinase is inactive

38
Q

Fructose 1,6-bisphosphate

A

activates pyruvate kinase

39
Q

ATP

A

allosterically inhibits pyruvate kinase

feed-forward activation