Creatine + phosphocreatine (PCr) form the high-energy phosphate buffer for cells with rapid ATP turnover (skeletal muscle, brain). Creatine kinase reversibly transfers a phosphate between ATP/ADP and PCr/Cr — under high-energy demand PCr → ATP within milliseconds (faster than glycolysis/oxidative phosphorylation can ramp). Endogenous creatine synthesis: glycine + arginine → guanidinoacetate (AGAT in kidney) → creatine (GAMT in liver, methyl group from SAM — cross-link: methionine_sam_cycle). Daily ~1-2 g endogenous + dietary turnover. Supplemental creatine monohydrate ~3-5 g/d saturates muscle PCr stores in ~30 days (slow-load) or 5-7 days (loading 20 g/d × 5d then maintenance). Documented benefits: anaerobic performance, muscle mass, possibly cognitive function under stress. Phosphocreatine system limits acidosis-driven fatigue at sprint-duration efforts. Cross-link: carnitine + carnitine_shuttle complements creatine for energy systems.
Organ Systems
musculoskeletal
nervous
Pathway Steps
glycine-and-arginine → guanidinoacetate — via AGAT (kidney + pancreas). AGAT (kidney/pancreas) transfers arginine’s amidino group to glycine — the committed, rate-limiting step of creatine synthesis, feedback-inhibited by creatine.
guanidinoacetate → creatine — via GAMT (liver) — SAM methyl donor. GAMT (liver) methylates guanidinoacetate using SAM; creatine synthesis is one of the body’s largest consumers of SAM methyl groups, so dietary creatine spares methylation capacity and lowers homocysteine generation.
creatine → phosphocreatine — via creatine kinase (mitochondrial + cytosolic isoforms). Creatine kinase reversibly stores high-energy phosphate as phosphocreatine, rapidly regenerating ATP during bursts of demand (the phosphagen system). Isoenzymes (CK-MM muscle, CK-MB heart, CK-BB brain) are clinical markers; creatine slowly cyclizes to creatinine for renal excretion.
Known Modulators
creatine (substrate) — PCr pool (skeletal muscle + CNS). creatine monohydrate — best-studied form; 3-5 g/d maintenance; ~30 days to saturation without loading
d ribose (substrate) — ATP/AMP regeneration (purine salvage). pentose; chronic-fatigue + CHF claims; biochemical rationale solid but clinical signal weak
peak atp (substrate) — oral ATP supplement (CFM-branded). oral ATP supplement; bioavailability problem since ATP doesn't cross cell membranes — claimed peripheral signaling effects