Glycolysis
High-Yield Summary
- Glycolysis: 1 glucose → 2 pyruvate, in the cytoplasm, with or without oxygen. Net yield: 2 ATP, 2 NADH.
- Two phases: energy-investment (spends 2 ATP to form fructose-1,6-bisphosphate, then splits into 2×G3P) and energy-payoff (produces 4 ATP total + 2 NADH from the two G3P).
- Three irreversible/regulated steps: hexokinase/glucokinase (glucose→G6P), PFK-1 (F6P→F1,6BP, rate-limiting), pyruvate kinase (PEP→pyruvate) — these are exactly what gluconeogenesis must bypass.
- PFK-1 inhibited by ATP/citrate, activated by AMP; PFK-2 makes fructose-2,6-bisphosphate, a potent PFK-1 activator (insulin up, glucagon down).
- Without O2, NAD⁺ is regenerated by fermentation: lactate dehydrogenase (mammals, pyruvate→lactate) or alcoholic fermentation (yeast, pyruvate→ethanol).
- Erythrocytes have no mitochondria — glycolysis is their only ATP source, and they divert 1,3-BPG into 2,3-BPG, which right-shifts the oxygen dissociation curve (promotes O2 unloading to tissues).
Key Terms
- Substrate-level phosphorylation
- Direct transfer of a phosphate to ADP by an enzyme (not via the ETC) — occurs twice in glycolysis.
- PFK-1
- Phosphofructokinase-1; rate-limiting enzyme of glycolysis, converts F6P to F1,6BP.
- Feed-forward activation
- An early pathway product activates a later enzyme — F1,6BP activates pyruvate kinase.
- 2,3-BPG
- Side product of glycolysis in RBCs; binds deoxyhemoglobin, lowers O2 affinity, promotes O2 release to tissues.
Glycolysis: 10 Steps
- 1Glucose → glucose-6-phosphate (hexokinase/glucokinase) — investment
- 2Glucose-6-phosphate → fructose-6-phosphate (phosphoglucose isomerase) — investment
- 3Fructose-6-phosphate → fructose-1,6-bisphosphate (PFK-1) — investment, rate-limiting
- 4Fructose-1,6-bisphosphate → G3P + DHAP (aldolase); DHAP → G3P (triose phosphate isomerase) — investment
- 5G3P → 1,3-bisphosphoglycerate + NADH (glyceraldehyde-3-P dehydrogenase) — payoff, ×2
- 61,3-BPG → 3-phosphoglycerate + ATP (3-phosphoglycerate kinase) — payoff, 1st substrate-level phosphorylation, ×2
- 73-phosphoglycerate → 2-phosphoglycerate (phosphoglycerate mutase) → PEP (enolase) — payoff, ×2
- 8PEP → pyruvate + ATP (pyruvate kinase) — payoff, 2nd substrate-level phosphorylation, ×2
Hexokinase vs. Glucokinase
| Feature | Hexokinase vs. Glucokinase |
|---|---|
| Location | Most tissues / Liver, pancreatic beta cells |
| Km / affinity | Low Km, high affinity / High Km, low affinity |
| Regulation | Inhibited by its product G6P / Not product-inhibited |
| Role | Steady glucose supply to brain/muscle / Liver glucose buffer; beta-cell glucose sensor with GLUT2 |
Net Yield Per Glucose
Glucose + 2 ADP + 2 Pi + 2 NAD⁺ → 2 Pyruvate + 2 ATP + 2 NADH
- 2 ATP = Net gain (4 produced in payoff − 2 spent in investment)
- 2 NADH = From oxidizing the two G3P molecules
- 2 Pyruvate = Final product, one per original G3P
- Runs in the cytoplasm, aerobic or anaerobic — the only pathway step that doesn't require oxygen or mitochondria.
Common MCAT Trap
- Facilitated diffusion of glucose in isn't glycolysis — glycolysis starts only after glucose is phosphorylated to G6P (trapped in the cell).
- The three irreversible steps are the SAME three steps gluconeogenesis bypasses with different enzymes — memorize this list once, use it twice.
- 2,3-BPG shifts the oxygen curve RIGHT (less affinity, more unloading) — don't confuse direction with a left shift.
Quick Recall
What is the net ATP and NADH yield of glycolysis per glucose?
Which enzyme is the rate-limiting step of glycolysis?
How do red blood cells generate ATP if they have no mitochondria?
What effect does 2,3-BPG have on hemoglobin's oxygen affinity?