I now have everything I need to build a complete, exam-ready glycolysis revision. Here it is:
Glycolysis & Carbohydrate Metabolism - MBBS Revision
PART 1 - Concise Notes
What is Glycolysis?
Glycolysis is the universal 10-step pathway in the cytosol that converts 1 glucose (6C) → 2 pyruvate (3C). It is the hub of carbohydrate metabolism - virtually all dietary sugars (fructose, galactose) are fed into it.
- Aerobic glycolysis: Pyruvate → Acetyl-CoA → TCA cycle (requires O2)
- Anaerobic glycolysis: Pyruvate → Lactate (no O2 needed - used by RBCs, cornea, exercising muscle)
PART 2 - The 10 Steps (Exam Table)
Phase 1 - ENERGY INVESTMENT (Steps 1-5) - costs 2 ATP
| Step | Reaction | Enzyme | Notes |
|---|
| 1 | Glucose → Glucose-6-P | Hexokinase (or Glucokinase in liver) | Irreversible; traps glucose in cell |
| 2 | G-6-P → Fructose-6-P | Phosphoglucose isomerase | Reversible |
| 3 | F-6-P → Fructose-1,6-bisP | Phosphofructokinase-1 (PFK-1) | Rate-limiting step; irreversible |
| 4 | F-1,6-bisP → DHAP + G-3-P | Aldolase | Splits 6C → two 3C |
| 5 | DHAP ⇌ G-3-P | Triose phosphate isomerase | Only G-3-P proceeds |
Phase 2 - ENERGY GENERATION (Steps 6-10) - produces 4 ATP + 2 NADH
| Step | Reaction | Enzyme | Notes |
|---|
| 6 | G-3-P + NAD⁺ → 1,3-bisphosphoglycerate | G-3-P dehydrogenase | Produces NADH; inhibited by arsenic |
| 7 | 1,3-BPG → 3-phosphoglycerate | Phosphoglycerate kinase | 1st substrate-level phosphorylation; makes ATP |
| 8 | 3-PG → 2-PG | Phosphoglycerate mutase | |
| 9 | 2-PG → Phosphoenolpyruvate (PEP) | Enolase | Inhibited by fluoride |
| 10 | PEP → Pyruvate | Pyruvate kinase | 2nd substrate-level phosphorylation; irreversible |
Net yield per glucose: 2 ATP + 2 NADH + 2 Pyruvate
PART 3 - The 3 Regulatory Enzymes (Most Exam-Favourite!)
1. Hexokinase vs Glucokinase
| Feature | Hexokinase (I-III) | Glucokinase (IV) |
|---|
| Location | All tissues | Liver, pancreatic β-cells |
| Km for glucose | Low (high affinity) | High (low affinity) |
| Inhibited by G-6-P? | Yes (product inhibition) | No |
| Induced by insulin? | No | Yes |
| Function | Works at low glucose | Works only when glucose is high (after meals) |
2. PFK-1 - The Rate-Limiting Enzyme
| Activated by | Inhibited by |
|---|
| AMP, ADP | ATP, Citrate |
| Fructose-2,6-bisphosphate (most potent activator) | Glucagon (via lowering F-2,6-bisP) |
| Low pH activates... | ...actually inhibits (protective in ischemia) |
Insulin raises F-2,6-bisP → activates PFK-1 → promotes glycolysis
Glucagon lowers F-2,6-bisP → inhibits PFK-1 → promotes gluconeogenesis
3. Pyruvate Kinase
- Activated by: F-1,6-bisP (feedforward activation)
- Inhibited by: ATP, Acetyl-CoA, glucagon (via phosphorylation)
- Deficiency: Hemolytic anemia (RBCs can't maintain ATP for Na/K pump)
PART 4 - ATP Yield Summary
| Condition | ATP per glucose |
|---|
| Anaerobic glycolysis | 2 ATP |
| Aerobic glycolysis (full oxidation) | ~30-32 ATP (older textbooks say 36-38) |
- Steps 1 & 3 consume 1 ATP each = 2 ATP used
- Steps 7 & 10 produce 1 ATP each × 2 (two 3C units) = 4 ATP made
- Net = 2 ATP (substrate-level phosphorylation)
PART 5 - Glucose Transporters (GLUTs) - High Yield!
| GLUT | Location | Special Feature |
|---|
| GLUT-1 | RBCs, brain, most tissues | Basal uptake; always present |
| GLUT-2 | Liver, kidney, pancreatic β-cells, small intestine | High Km - glucose sensor |
| GLUT-3 | Brain (neurons) | High affinity - brain gets glucose first |
| GLUT-4 | Muscle, adipose | Insulin-stimulated - most clinically important |
| GLUT-5 | Small intestine | Transports fructose |
PART 6 - Fates of Pyruvate
┌─→ Acetyl-CoA (aerobic) → TCA cycle
Glucose → Pyruvate ─┤
├─→ Lactate (anaerobic)
├─→ Alanine (transamination)
├─→ Oxaloacetate (gluconeogenesis via pyruvate carboxylase)
└─→ Ethanol (yeast/microorganisms)
PART 7 - High-Yield Bullet Points
- Fluoride inhibits enolase (step 9) - used in blood collection tubes to prevent glycolysis
- Arsenic inhibits G-3-P dehydrogenase (step 6) - uncouples substrate-level phosphorylation
- RBCs have no mitochondria - depend entirely on anaerobic glycolysis
- 2,3-BPG (made from 1,3-BPG via Luebering-Rapoport shunt) decreases Hb O2 affinity - important in RBCs
- Pasteur effect: O2 inhibits anaerobic glycolysis (O2 presence → less lactate production)
- Warburg effect: Cancer cells prefer glycolysis even in presence of O2 (aerobic glycolysis)
- Lactic acidosis: occurs when pyruvate → lactate accumulates (shock, thiamine deficiency, metformin OD)
PART 8 - Quick Q&A Drill
Q1. Which enzyme is the main regulatory/rate-limiting enzyme of glycolysis?
PFK-1 (phosphofructokinase-1)
Q2. Why can RBCs only do anaerobic glycolysis?
No mitochondria - cannot do oxidative phosphorylation or TCA
Q3. What is the most potent activator of PFK-1?
Fructose-2,6-bisphosphate (produced by PFK-2, activated by insulin)
Q4. Glucokinase vs Hexokinase - which works after a big carbohydrate meal?
Glucokinase - it has high Km so only fires when glucose is high
Q5. What happens to NADH produced in glycolysis if there is no O2?
It is reoxidized to NAD⁺ when pyruvate is reduced to lactate by lactate dehydrogenase (LDH) - this regenerates NAD⁺ to keep glycolysis running
Q6. Name the 3 irreversible steps of glycolysis.
Steps 1, 3, 10 - catalyzed by Hexokinase, PFK-1, Pyruvate kinase
Q7. A patient with pyruvate kinase deficiency presents with hemolytic anemia. Why?
RBCs need ATP from PK for the Na⁺/K⁺-ATPase pump to maintain cell shape. Without PK, ATP falls → cell swells → hemolysis
Sources: Lippincott Illustrated Reviews: Biochemistry 8e | Harper's Illustrated Biochemistry 32e | Basic Medical Biochemistry: A Clinical Approach 6e
What next? We can:
- Go deeper into the TCA cycle (follows glycolysis directly)
- Move to glycogen metabolism (glycogenesis + glycogenolysis)
- Do gluconeogenesis (the reverse pathway - bypasses the 3 irreversible steps)
- Quiz you more on glycolysis before moving on
What would you like?