Biochemistry · Topic
Creatine, phosphocreatine and creatinine !
Creatine is made from three amino acids and stores quick energy in muscle as phosphocreatine. Its waste product, creatinine, shows how well the kidneys filter.
Updated 2026-11-01
Key facts
- Three amino acids: arginine and glycine form guanidinoacetate (AGAT, mainly kidney); SAM methylates it to creatine (GAMT, mainly liver).
- Creatine travels in blood and enters muscle and brain through the creatine transporter (SLC6A8); 95 % of the body's creatine is in skeletal muscle.
- Creatine kinase: creatine + ATP ⇌ phosphocreatine + ADP; at rest it stores energy, and in the first seconds of effort it regenerates ATP.
- About 2 % of creatine and phosphocreatine turns into creatinine each day by a non-enzymatic cyclisation; creatinine output is proportional to muscle mass.
- Creatinine is filtered freely by the glomerulus (with a little tubular secretion) and not reabsorbed, so serum creatinine is used to estimate GFR.
In detail
- 1. Kidney: L-arginine:glycine amidinotransferase (AGAT, gene GATM) moves the amidino group of arginine to glycine → guanidinoacetate + ornithine.
- 2. Liver: guanidinoacetate methyltransferase (GAMT) adds a methyl from SAM → creatine + S-adenosylhomocysteine; this is one of the biggest consumers of methyl groups.
- 3. Creatine kinase isoenzymes: CK-MM (skeletal muscle), CK-MB (heart), CK-BB (brain) and a mitochondrial form that links ATP made in mitochondria to phosphocreatine (the phosphocreatine shuttle).
- 4. Phosphocreatine lasts about 10 seconds of maximal effort, bridging the gap until glycolysis speeds up.
- 5. Creatinine is formed at a steady rate, so a 24-hour urine creatinine checks that a collection is complete.
- 6. Dietary creatine (meat, fish) and supplements reduce the body's own synthesis (AGAT is repressed by creatine).
- Also called
- Creatine synthesis, Creatine kinase shuttle
Clinical notes
- Serum creatinine rises when GFR falls, but only after about half of kidney function is lost; it also depends on muscle mass, age and sex.
- Creatine deficiency syndromes (AGAT, GAMT, transporter) cause intellectual disability and seizures; brain MR spectroscopy shows a missing creatine peak.
- CK in blood rises with muscle damage (rhabdomyolysis, myositis, muscular dystrophy); CK-MB was used for myocardial infarction.
Related conditions
- Guanidinoacetate methyltransferase (GAMT) deficiency
- Chronic kidney disease
- Acute kidney injury
- Duchenne muscular dystrophy
Related
- Creatine
- Creatinine
- S-adenosylmethionine (SAM)
- Molecules derived from amino acids
- ATP (adenosine triphosphate)
- Isoenzymes
- Urea cycle
- Creatinine and estimated glomerular filtration rate (eGFR)
- Creatine kinase (CK) and CK-MB as lab tests
Test yourself
Think of the answer, then tap the question to see it.
Which three amino acids are needed to make creatine?
Arginine and glycine (forming guanidinoacetate) and methionine, as SAM, which gives the methyl group.
Where are the two steps of creatine synthesis mainly carried out?
AGAT acts mainly in the kidney and GAMT mainly in the liver.
Why does serum creatinine depend on muscle mass?
Creatinine forms non-enzymatically from muscle creatine and phosphocreatine at a steady rate, so more muscle means more creatinine.
What reaction does creatine kinase catalyse?
Creatine + ATP ⇌ phosphocreatine + ADP; during intense effort it runs backward to regenerate ATP.
What does brain MR spectroscopy show in creatine deficiency syndromes?
A missing or very low creatine peak.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Guanidinoacetate methyltransferase deficiency: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); GATM: Glycine amidinotransferase, mitochondrial (human) (UniProt, 2026); GAMT: Guanidinoacetate N-methyltransferase (human) (UniProt, 2026); Creatinine blood test: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.