Learn / Metabolism
Metabolic pathways
Every FMK pathway as a clickable map. Pick one pathway to hammer it — next step, enzyme, regulator, cofactor, and the facts that get tested (NADPH and who needs it, rate-limiting steps, deficiencies) — or set it to all pathways for a mixed drill. Every answer says which enzyme and which pathway.
Glycolysis · Cytosol (all cells). Enzymes sit beside the arrows; a ★ marks the rate-limiting step. The map scrolls inside its panel.
Zoom
Glycolysis
Glucose → 2 pyruvate. Net 2 ATP + 2 NADH per glucose. Three irreversible steps (hexokinase/glucokinase, PFK-1 ★, pyruvate kinase); PFK-1 is rate-limiting. RBCs depend on it entirely — no mitochondria.
Click any metabolite on the map for its reactions. Source: FMK-02.1 Glycolysis & TCA.
Reactions
| Step | Enzyme | Cofactors | Regulation |
|---|---|---|---|
| Glucose → Glucose-6-phosphate | Hexokinase / Glucokinase Hexokinase deficiency — rare hemolytic anemia (RBCs lose their only ATP source) Hexokinase deficiency → |
ATP → ADP | − Glucose-6-phosphate (hexokinase only) |
| Glucose-6-phosphate → Fructose-6-phosphate | Phosphoglucose isomerase | — | |
| Fructose-6-phosphate → Fructose-1,6-bisphosphate | Phosphofructokinase-1 (PFK-1) ★ PFK-1 deficiency (Tarui disease) — exercise cramps/myopathy, hemolytic anemia, hyperuricemia PFK-1 deficiency (Tarui disease, GSD VII) → |
ATP → ADP | + AMP; ADP; Fructose-2,6-bisphosphate (most potent; made by PFK-2) − ATP; Citrate |
| Fructose-1,6-bisphosphate → DHAP | Aldolase A | — | |
| Fructose-1,6-bisphosphate → Glyceraldehyde-3-phosphate | Aldolase A | — | |
| DHAP → Glyceraldehyde-3-phosphate | Triose phosphate isomerase | — | |
| Glyceraldehyde-3-phosphate → 1,3-Bisphosphoglycerate | Glyceraldehyde-3-phosphate dehydrogenase | NAD⁺ → NADH, Pi | |
| 1,3-Bisphosphoglycerate → 3-Phosphoglycerate | Phosphoglycerate kinase | ADP → ATP (substrate-level) | |
| 1,3-Bisphosphoglycerate → 2,3-BPG (RBC) | Bisphosphoglycerate mutase (RBC) | — | |
| 3-Phosphoglycerate → 2-Phosphoglycerate | Phosphoglycerate mutase | — | |
| 2-Phosphoglycerate → Phosphoenolpyruvate | Enolase | — | − Fluoride |
| Phosphoenolpyruvate → Pyruvate | Pyruvate kinase Pyruvate kinase deficiency — most common glycolytic enzyme defect; chronic hemolytic anemia with echinocytes (burr cells), splenomegaly, ↑ reticulocytes; heterozygotes resist P. falciparum Pyruvate kinase (PK) deficiency → |
ADP → ATP (substrate-level) | + Fructose-1,6-bisphosphate (feed-forward) − ATP; Alanine; Glucagon (phosphorylation via PKA, liver isoform) |
| Pyruvate → Lactate | Lactate dehydrogenaseWarburg effect (cancer aerobic glycolysis) → | NADH → NAD⁺ | |
| Pyruvate → Acetyl-CoA (→ TCA) | Pyruvate dehydrogenase complex | TPP (B₁), Lipoic acid, CoA (B₅), FAD (B₂), NAD⁺ (B₃) |
Conditions that live on this map
Arsenic poisoningFanconi-Bickel syndrome (GLUT2 deficiency)GLUT1 deficiency (epileptic disorder)Hexokinase deficiencyPFK-1 deficiency (Tarui disease, GSD VII)Pyruvate kinase (PK) deficiencySGLT-2 inhibitors (gliflozins: empagliflozin, dapagliflozin)Type 2 diabetes / insulin resistanceWarburg effect (cancer aerobic glycolysis)
Blue pills sit on one specific arrow; grey ones are whole-pathway problems. Each opens the full condition card, which links back here with the arrow lit.
Facts worth knowing
Yield
- Net ATP per glucose from glycolysis alone (anaerobic) — 2 ATP (4 made − 2 spent)
- NADH produced per glucose in glycolysis — 2 NADH (at the GAPDH step)
- Total aerobic ATP per glucose (glycolysis + PDH + TCA + OXPHOS) — ~30–32 ATP (2.5 per NADH, 1.5 per FADH₂; shuttle-dependent)
Transporter
- Insulin-dependent glucose transporter (muscle & adipose) — GLUT-4 (Fails to translocate in T2DM / insulin deficiency → glucose stays in blood.)
- Bidirectional, low-affinity (Km 15–20 mM) transporter of liver, kidney & β-cells — GLUT-2 (Lets the liver and β-cell 'sense' glucose only when it's high.)
- Basal uptake transporter of most tissues and the blood-brain barrier — GLUT-1 (GLUT-1 deficiency: low CSF glucose with normal blood glucose, infantile seizures; treat with ketogenic diet.)
- High-affinity neuronal glucose transporter — GLUT-3
- Fructose transporter of the small intestine — GLUT-5
- Na⁺-coupled renal transporter blocked by gliflozins — SGLT-2 (Reabsorbs ~90% of filtered glucose; blocking it → glucosuria, weight loss, cardioprotection.)
Toxin
- Arsenite (As³⁺) inactivates which cofactor? — Lipoic acid (→ PDH, α-KG DH and branched-chain α-keto acid DH fail)
- Arsenate (As⁵⁺) competes with which substrate? — Inorganic phosphate at the GAPDH step (uncouples glycolysis from ATP synthesis)
Enzyme deficiency
- Deficiency of Hexokinase / Glucokinase causes… — Hexokinase deficiency — rare hemolytic anemia (RBCs lose their only ATP source) (Hexokinase (HK I–III): all tissues, high affinity (Km ~0.1 mM), low Vmax, feedback-inhibited by G6P. Glucokinase (HK IV): liver & β-cells, low affinity (Km ~10 mM), high Vmax, induced by insulin — a glucose sensor that only works after a meal.)
- Deficiency of Phosphofructokinase-1 (PFK-1) causes… — PFK-1 deficiency (Tarui disease) — exercise cramps/myopathy, hemolytic anemia, hyperuricemia (The committed, rate-limiting step. Fed state: insulin → PFK-2 dephosphorylated & active → ↑F2,6-BP → PFK-1 on. Fasting: glucagon → PKA phosphorylates the bifunctional enzyme → FBPase-2 active → ↓F2,6-BP → PFK-1 off (liver).)
- Deficiency of Pyruvate kinase causes… — Pyruvate kinase deficiency — most common glycolytic enzyme defect; chronic hemolytic anemia with echinocytes (burr cells), splenomegaly, ↑ reticulocytes; heterozygotes resist P. falciparum (Second substrate-level phosphorylation. Hepatic isoform is switched off by glucagon so PEP is diverted to gluconeogenesis.)
Rate-limiting step
- Rate-limiting enzyme of glycolysis — Phosphofructokinase-1 (PFK-1) (The committed, rate-limiting step. Fed state: insulin → PFK-2 dephosphorylated & active → ↑F2,6-BP → PFK-1 on. Fasting: glucagon → PKA phosphorylates the bifunctional enzyme → FBPase-2 active → ↓F2,6-BP → PFK-1 off (liver).)