GLYCOLYSIS

 

GLYCOLYSIS – Full Process (Embden–Meyerhof–Parnas Pathway)

Glycolysis is a 10-step metabolic pathway occurring in the cytoplasm, where one molecule of glucose (6-C) is converted into two molecules of pyruvate (3-C) with the production of ATP and NADH.


PHASES OF GLYCOLYSIS

Glycolysis has two phases:

  1. Energy Investment Phase (Steps 1–5)
    – 2 ATP are used
    – Glucose is phosphorylated and split into two 3-carbon sugars

  2. Energy Payoff Phase (Steps 6–10)
    – 4 ATP and 2 NADH are produced
    – 2 pyruvate molecules formed


STEPS OF GLYCOLYSIS (10 Steps)

Phase I – Energy Investment


Step 1: Phosphorylation of Glucose

Enzyme: Hexokinase
Reaction: Glucose → Glucose-6-phosphate (G6P)
ATP Used: 1
Purpose: Traps glucose inside the cell.


Step 2: Isomerization

Enzyme: Phosphoglucose isomerase
Reaction: G6P → Fructose-6-phosphate (F6P)
Forms a keto sugar required for next phosphorylation.


Step 3: Second Phosphorylation (Key Regulatory Step)

Enzyme: Phosphofructokinase-1 (PFK-1)
Reaction: F6P → Fructose-1,6-bisphosphate (F1,6BP)
ATP Used: 1
Rate-limiting step of glycolysis.


Step 4: Cleavage of F1,6BP

Enzyme: Aldolase
Reaction: F1,6BP → DHAP + G3P
(DHAP = Dihydroxyacetone phosphate, G3P = Glyceraldehyde-3-phosphate)


Step 5: Isomerization

Enzyme: Triose phosphate isomerase
Reaction: DHAP → G3P
Now 2 molecules of G3P proceed to phase II.


Phase II – Energy Payoff


Step 6: Oxidation and NADH formation

Enzyme: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
Reaction: G3P → 1,3-BPG (1,3-bisphosphoglycerate)
Produces: 2 NADH (one per G3P)


Step 7: ATP Formation (Substrate-Level Phosphorylation)

Enzyme: Phosphoglycerate kinase
Reaction: 1,3-BPG → 3-PG
ATP Produced: 2 ATP (one per G3P)
First ATP-yielding step.


Step 8: Mutase Reaction

Enzyme: Phosphoglycerate mutase
Reaction: 3-PG → 2-PG


Step 9: Dehydration

Enzyme: Enolase
Reaction: 2-PG → PEP (Phosphoenolpyruvate)
Forms a high-energy compound.


Step 10: Second ATP Formation & Pyruvate Formation

Enzyme: Pyruvate kinase
Reaction: PEP → Pyruvate
ATP Produced: 2 ATP
Highly exergonic reaction.


NET GAIN OF GLYCOLYSIS

ItemAmount
ATP used2
ATP produced4
NET ATP2 ATP
NADH produced2 NADH
End Product2 Pyruvate

REGULATION OF GLYCOLYSIS (Important for exams)

Major regulatory enzymes:

  • Hexokinase (Step 1) – inhibited by G6P

  • PFK-1 (Step 3) – main regulatory enzyme; inhibited by ATP and citrate; activated by AMP

  • Pyruvate kinase (Step 10) – inhibited by ATP; activated by fructose-1,6-bisphosphate


FATE OF PYRUVATE

Depending on oxygen availability:

1. Aerobic:

Pyruvate → Acetyl-CoA → enters TCA cycle

2. Anaerobic (animals):

Pyruvate → Lactate

3. Anaerobic (yeast):

Pyruvate → Ethanol + CO₂

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