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.
Glycogen synthesis & breakdown · Cytosol — liver (blood glucose) and muscle (own fuel). Enzymes sit beside the arrows; a ★ marks the rate-limiting step. The map scrolls inside its panel.
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Glycogen synthesis & breakdown
Synthesis: G6P → G1P → UDP-glucose → α(1→4) chains by glycogen synthase, α(1→6) branches by branching enzyme. Breakdown: glycogen phosphorylase (rate-limiting) releases G1P to the limit dextrin, then debranching enzyme. Liver has glucose-6-phosphatase and exports glucose; muscle doesn't. Glucagon/epinephrine → cAMP → PKA flips phosphorylase ON and synthase OFF; insulin does the opposite via PP1.
Click any metabolite on the map for its reactions. Source: FMK-03.6 Glycogen metabolism.
Reactions
| Step | Enzyme | Cofactors | Regulation |
|---|---|---|---|
| Glucose → Glucose-6-phosphate | Hexokinase (muscle) / Glucokinase (liver) | ATP → ADP | |
| Glucose-6-phosphate → Glucose-1-phosphate | Phosphoglucomutase | — | |
| Glucose-1-phosphate → UDP-glucose | UDP-glucose pyrophosphorylase | UTP → PPi | |
| UDP-glucose → α(1→4) chain (glycogenin primer) | Glycogen synthase ★ | — | + Insulin (PP1 dephosphorylation → synthase a); Glucose-6-phosphate (allosteric, even the b form) − Glucagon / epinephrine (PKA phosphorylation → synthase b) |
| α(1→4) chain (glycogenin primer) → Branched glycogen | Branching enzyme (4:6 transferase) Andersen disease (GSD IV) — abnormal, poorly branched glycogen; cirrhosis and early hepatic failure Andersen disease (GSD Type IV) → |
— | |
| Branched glycogen → Limit dextrin (4 residues from branch) | Glycogen phosphorylase ★ McArdle (GSD V, muscle isoform): exercise cramps, myoglobinuria, 'second wind', normal blood glucose. Hers (GSD VI, liver isoform): mild hypoglycemia, hepatomegaly, benign McArdle disease (glycogen storage disease type V) →Hers disease (GSD Type VI) → |
PLP (B₆), Pi | + Glucagon (liver) & epinephrine (via cAMP → PKA → phosphorylase kinase → phosphorylase a); AMP (muscle b form); Ca²⁺-calmodulin (muscle, via phosphorylase kinase) − Insulin (PP1 → phosphorylase b); ATP; Glucose-6-phosphate; Free glucose (liver only) |
| Branched glycogen → Glucose-1-phosphate (released) | Glycogen phosphorylaseMcArdle disease (glycogen storage disease type V) →Hers disease (GSD Type VI) → | PLP (B₆), Pi | |
| Limit dextrin (4 residues from branch) → Free glucose (from α1→6 bond) | Debranching enzyme — α(1→6) glucosidase activity Cori disease (GSD III) — milder fasting hypoglycemia, hepatomegaly, limit dextrin accumulates; gluconeogenesis intact Cori disease (GSD Type III) → |
— | |
| Limit dextrin (4 residues from branch) → Glucose-1-phosphate (released) | Debranching enzyme — 4:4 transferase activity | — | |
| Glucose-1-phosphate (released) → Glucose-6-phosphate (from breakdown) | Phosphoglucomutase | — | |
| Glucose-6-phosphate (from breakdown) → Blood glucose (liver only) | Glucose-6-phosphatase (liver, ER) Von Gierke disease (GSD I) — severe fasting hypoglycemia, lactic acidosis, hyperuricemia, hyperlipidemia; blocks glycogenolysis AND gluconeogenesis Von Gierke disease (GSD type I; secondary hyperuricemia) → |
— | |
| Glucose-6-phosphate (from breakdown) → Glycolysis (muscle) | Glycolysis (muscle keeps its G6P) | — |
Conditions that live on this map
Andersen disease (GSD Type IV)Cori disease (GSD Type III)Hers disease (GSD Type VI)Hypoglycemia in counter-regulatory hormone deficiency (glucagon, epinephrine/adrenal insufficiency, cortisol)McArdle disease (glycogen storage disease type V)Pompe disease (GSD Type II)Von Gierke disease (GSD type I; secondary hyperuricemia)
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
Regulation
- Insulin turns glycogen synthesis on by — Activating phosphodiesterase (↓cAMP) and protein phosphatase-1 → dephosphorylates synthase (ON) and phosphorylase (OFF)
- Glucagon/epinephrine turn glycogenolysis on by — GPCR → adenylyl cyclase → cAMP → PKA → phosphorylase kinase → phosphorylase a; PKA also phosphorylates synthase (OFF) and inhibitor-1 (locks PP1 out)
- Muscle glycogenolysis starts within seconds of contraction because — Ca²⁺ binds the calmodulin subunit of phosphorylase kinase b — no cAMP needed; AMP also activates phosphorylase b directly
- Liver-only allosteric inhibitor of glycogen phosphorylase — Free glucose — the liver stops releasing glucose once blood glucose is adequate
- Why liver glycogen raises blood glucose but muscle glycogen doesn't — Liver has glucose-6-phosphatase; muscle lacks it, so G6P is trapped and used in glycolysis
Yield
- Energy cost per glucose added to glycogen — 1 ATP (hexokinase) + 1 UTP (UDP-glucose) ≈ 2 ATP equivalents
- How long hepatic glycogen lasts in a fast — Roughly 12–24 hours; after that gluconeogenesis (and ketones) take over
Enzyme deficiency
- The only glycogen storage disease that is a lysosomal storage disease — Pompe (GSD II) — acid α-glucosidase/acid maltase; cardiomegaly, hypotonia, early death; cytosolic glycogen metabolism is normal
- GSD with normal blood glucose but exercise cramps and myoglobinuria — McArdle (GSD V, muscle glycogen phosphorylase) — 'second wind' when blood glucose and fatty acids arrive
- GSD with mild hypoglycemia because gluconeogenesis is intact — Hers (GSD VI, liver phosphorylase) and Cori (GSD III, debranching enzyme)
- GSD with the worst hypoglycemia, plus lactic acidosis, hyperuricemia, hyperlipidemia — Von Gierke (GSD I, glucose-6-phosphatase) — both glucose-releasing pathways are blocked
- Deficiency of Branching enzyme (4:6 transferase) causes… — Andersen disease (GSD IV) — abnormal, poorly branched glycogen; cirrhosis and early hepatic failure (Moves 6–8 residues to make an α(1→6) branch. Branches ↑ solubility and ↑ non-reducing ends for fast release.)
- Deficiency of Glycogen phosphorylase causes… — McArdle (GSD V, muscle isoform): exercise cramps, myoglobinuria, 'second wind', normal blood glucose. Hers (GSD VI, liver isoform): mild hypoglycemia, hepatomegaly, benign (Rate-limiting step of breakdown. Cleaves α(1→4) bonds phosphorolytically (no ATP needed) and stops 4 residues from a branch.)
- Deficiency of Debranching enzyme — α(1→6) glucosidase activity causes… — Cori disease (GSD III) — milder fasting hypoglycemia, hepatomegaly, limit dextrin accumulates; gluconeogenesis intact (After the 4:4 transferase moves three residues, the last α(1→6) glucose is hydrolysed as FREE glucose (~10% of output).)
- Deficiency of Glucose-6-phosphatase (liver, ER) causes… — Von Gierke disease (GSD I) — severe fasting hypoglycemia, lactic acidosis, hyperuricemia, hyperlipidemia; blocks glycogenolysis AND gluconeogenesis
Rate-limiting step
- Rate-limiting enzyme of glycogen synthesis & breakdown — Glycogen synthase (Rate-limiting step of synthesis. Adds α(1→4) glucose to a non-reducing end; needs glycogenin as the primer.)
- Rate-limiting enzyme of glycogen synthesis & breakdown — Glycogen phosphorylase (Rate-limiting step of breakdown. Cleaves α(1→4) bonds phosphorolytically (no ATP needed) and stops 4 residues from a branch.)