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Glycolysis Flashcards

(45 cards)

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1
Q

Describe what glycolysis is

A
  • Glycolysis: Catabolism (breakdown) of glucose to pyruvate under aerobic conditions converting from C6 glucose into 2 C3 pyruvates.
  • Free energy released from this process is harvested to synthesize ATP from ADP & Pi
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2
Q

Glycolysis can be divide into 2 stages

A

Stage 1: Energy Investment

  • C6 glucose (hexose) is phosphorylated and cleaved to yield 2 molecules of (triose) C3 glyceraldehydes-3-phosphate (GAP)
  • Consume 2 ATPs

Stage 2: Energy recovery

  • The 2 molecules of GAP are converted to pyruvate
  • Generate 4 ATPs
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3
Q

Summary of glucose metabolism

A

Overall rxn: Glucose + 2NAD+ + 2ADP + Pi → 2 pyruvates + 2ATP + 2NADH + 2H2O + 2H+

  • Glucose metabolism can be separated into 2 parts: Glycolysis and pyruvate metabolism
  • Glycolysis involve 10 reactions where C6 glucose is converted into 2 pyruvates
  • Then the pyruvate will undergo either aerobic or anaerobic metabolism
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4
Q

Explain reaction 1 involved in glycolysis

A

Hexokinase: 1st ATP utilization
(Glucose→G6P)
conversion of glucose to form glucose-6-phosphate (G6P)
- HK catalyzed the transfer of one phosphoryl group from ATP to glucose to form G6P
- The reaction requires Mg2+ or Mn2+ (bond to ATP’s phosphate oxygen atoms and shield their -ve charges for it to be more favorable of nucleophilic attack of C6-OH group of glucose)

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5
Q

Explain reaction 2 involved in glycolysis

A 
Phosphoglucose Isomerase (PGI)
(G6P→F6P)
Isomerization of G6P (aldose) to form F6P (ketose)
  • Involve ring opening and ring closure between C1 & O
  • Reaction is catalyzed by phosphoglucose isomerase
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6
Q

Explain reaction 3 involved in glycolysis

A

Phosphofructokinase (PFK): 2nd ATP Utilization
(F6P→FBP)
Conversion of F6P to form FBP (fructose-1,6-biphosphate)
- PFK catalyzing the nucleophilic attack of C1-OH group of F6P on the electrophilic phosphorus atom of Mg2+-ATP complex
- Biphosphate since the phosphoryl groups are not linked
- Non-equilibrium reaction

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7
Q

Explain reaction 4 involved in glycolysis

A

Aldolase (aldol cleavage)
(FBP → GAP + DHAP)
Cleavage of FBP to form two trioses, GAP and DHAP

  • Aldolase catalyze the aldol cleavage between C3 and C4 which require carbonyl at C2 and hydroxyl at C4.
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8
Q

Explain reaction 5 involved in glycolysis

A
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9
Q

Explain reaction 6 involved in glycolysis

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10
Q

Explain reaction 7 involved in glycolysis

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11
Q

Explain reaction 8 involved in glycolysis

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12
Q

Explain reaction 9 involved in glycolysis

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13
Q

Explain reaction 10 involved in glycolysis

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14
Q

What is the overall reaction of glycolysis?

A

Glucose+2NAD+2ADP+Pi —-> 2NADH+2Pyruvate+2ATP+ 2HO2 + 4H

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15
Q

Which reactions are non-equilibrium?

A

Reaction 1 : Glucose to G6P by HK
Reaction 3 : F6P to FBP by PFK
Reaction 10 : PEP to pyruvate by PK

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16
Q

List the three products of glycolysis

A

1) ATP
2) NADH
3) Pyruvate

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17
Q

ATP

A
  • 2 ATP per molecule of glucose were invested and subsequently 4ATP were
    generated, giving a net yield of 2ATP per glucose
  • ATP produced satisfies most of the cell’s energy needs.
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18
Q

NADH

A
  • 2 NAD+ are reduced to 2 NADH
  • Reduced NADH represent a source of free energy that can be recovered by
    subsequent oxidation
  • Under aerobic condition, electron pass from reduced coenzymes thru’ a series
    of electron carriers to the final oxidizing agent, O2, in a process known as
    electron transport
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19
Q

Pyruvate

Study These Flashcards
A
  • 2 pyruvate molecules are produced
  • Under aerobic condition, pyruvate will be completely oxidized to CO2 and H2O via citric acid cycle and oxidative phosphorylation, where ATP is
    generated
  • Under anaerobic metabolism, pyruvate is metabolized to a lesser extent to
    regenerate NAD+, via a process known as fermentation
20
Q

In Glycolysis, the reactions catalyzed by the following enzymes are candidates for flux control points:

Study These Flashcards
A
  • hexokinase (Reaction 1)
  • phosphofructokinase (Reaction 3)
  • pyruvate kinase (Reaction 10)
21
Q

Why are they the candidates for flux control points?

Study These Flashcards
A
  • They function far from equilibrium
  • The reactions are metabolically irreversible
  • They function with large negative free energy changes
22
Q

Which one is the primary flux control point for glycolysis?

23
Q

PFK control the flux via 2 mechanisms

Study These Flashcards
A
  1. Allosteric control

2. Substrate cycles

24
Q

Explain how PFK control the flux via allosteric control

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A
  • PFK is a tetrameric enzyme
  • Each PFK subunit has two binding sites for ATP: a substrate site and an inhibitor site
  • ATP is both a substrate as well as an allosteric inhibitor of this enzyme
  • At high ATP concentration, it become an allosteric inhibitor of PFK
  • ATP regulate PFK, thus control the glycolytic flux
  • ADP and AMP (including F2,6BP) reverse the inhibitory effect of enzyme, therefore they are activators
  • Concentration of ATP is high because of low metabolic demand, PFK is inhibited and the flux thru’ glycolysis is low
  • Concentration of ATP is low, the flux through pathway is high; and ATP is synthesised to replenish the pool
25
Define substrate cycle
Substrate cycling is a set of opposing, non equilibrium reactions catalyzed by different enzymes which act simultaneously, with at least one of the reactions driven by ATP hydrolysis.
26
What are the results of the substrate cycle?
The results of the cycle are that ATP is depleted, heat is produced, and no net substrate-to-product conversion is achieved.
27
Explain substrate cycling in the regulation of PFK
- In resting muscle, both enzymes in the F6P/FBP substrate cycle are active, and glycolytic flux is low - In active muscle, PFK activity increases while FBPase activity decreases. This dramatically increases the flux through PFK and therefore results in high glycolytic flux
28
Explain pyruvate metabolism
- Under aerobic conditions, pyruvate is oxidized by the citric acid cycle and oxidative phosphorylation to produce CO2 and H2O - Under anaerobic conditions, pyruvate undergo fermentation, to produce reduced end products
29
What happens in the muscle, for pyruvate metabolism?
Pyruvate is reduced to lactate to regenerate NAD* in a process known as homolactic fermentation
30
What happens in yeast, for pyruvate metabolism?
Pyruvate is decarboxylated to yield CO2 and acetyldehyde, which is then reduced by NADH to yield NAD* and ethanol. This process is known as alcoholic fermentation.
31
Explain homolactic fermentation
- In muscle, under anaerobic condition e.g., during vigorous activity when the demand for ATP is high and O2 is in short supply: - NADH is oxidised by pyruvate to generate NAD+ and lactate by lactate dehydrogenase (LDH) - The reaction is reversible, so pyruvate and lactate level are readily equilibrated - The overall process of an anaerobic glycolysis in muscle can be represented as: Glucose + 2 ADP + 2Pi ---> 2 Lactate + 2 ATP The lactate may be: - Exported out of the cell by blood to the liver where it is used to synthesise glucose, OR - Converted back to pyruvate, to enter the pathway for further degradation
32
Explain alcoholic fermentation
In yeast, under anaerobic condition, pyruvate is converted to ethanol and CO2 while regenerating NAD+ - Yeast produces ethanol and CO2 via 2 consecutive reactions: - The carboxylation of pyruvate to form acetaldehyde and CO2 as catalyzed by pyruvate decarboxylase (enzyme not present in animals), then - The reduction of acetaldehyde to ethanol by NADH as catalysed by alcohol dehydrogenase, thereby generating NAD+
33
What is the overall reaction in alcoholic fermentation?
Glucose + 2Pi +2ADP ---> 2 Ethanol + 2CO2 + 2ATP
34
What is the overall reaction in homolactic fermentation
Glucose + 2Pi +2ADP ---> 2 Lactate + 2ATP
35
What is pentose phosphate pathway?
- An alternative mode of glucose oxidation where G6P is converted to R5P or hexoses to pentoses, - R5P and its derivatives are required for the synthesis of RNA, DNA, etc. - The pathway produced NADPH
36
Which tissues are rich in the PPP enzymes
Tissues that are most heavily involved in lipid biosynthesis | - liver, mammary gland, adipose tissue, adrenal cortex
37
What is the overall reaction of the pentose phosphate pathway?
3G6P + 6 NADP+ + 3H2O ----> 6NADPH + 6 H+ + 3CO2 + 2F6P + GAP
38
Pentose Phosphate pathway occurs in 3 stages. Explain stage 1
Stage 1: Oxidative reaction (Rxn 1-3) which yield NADPH and ribulose-5-phosphate (Ru5P) 3G6P + 6NADP+ + 3H2O ---> 6NADPH + 6H+ + 3CO2 + 3Ru5P - G6P generated from hexokinase on glucose (glycolysis) or glycogen breakdown - Only Rxn 1-3 of pathway are involved in the production of NADPH - 2 molecules of NADPH are generated per 1 molecule of G6P that enter pathway
39
Explain the stage 2 of PPP
Isomerization and epimerization reaction (Rxn 4 and 5) which transform Ru5P either to ribose-5-phosphate (R5P) or xylose-5-phosphate (Xu5P) 3 Ru5P ---> R5P + 2Xu5P
40
Explain stage 3 for PPP
A series of C-C bond cleavage and formation rxn (Rxn 6-8) that convert 2 molecules of Xu5P and one molecule of R5P to 2 molecules of F6P and one molecule of GAP Includes transketolase and transaldolase
41
What are the principal products of PPP?
NADH and R5P
42
The flux through the PPP and thus the rate of NADPH production is controlled by?
The rate of the G6PD reaction
43
The activity of G6PD which catalyzes the pathway's first committed step is regulated by?
The concentration of NADP+
44
What happens when the cell consumes NADPH for PPP?
NADP+ concentration rises, increasing the rate of G6PD reaction and thereby stimulating NADPH regeneration
45
A genetic deficiency in G6PD leads to?
Hemolytic anemia on administration of the antimalarial drug primaquine

Biochemistry (10 decks)

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