Here is a detailed breakdown of the organs involved in the successive stages of creatine synthesis, sourced directly from the textbooks:
Creatine Synthesis: Organs and Stages
Creatine is synthesized in a two-step pathway distributed across two organs: the kidney and the liver.
Stage 1 - Kidney (Step 1)
Organ: Kidneys
Enzyme: Arginine:glycine amidinotransferase (transamidinase)
Substrates: Arginine + Glycine
Products: Guanidinoacetate + Ornithine
In the kidney, the guanidinium group of arginine is transferred to glycine. This produces guanidinoacetate (also called glycocyamine) and releases ornithine as a byproduct. Guanidinoacetate then travels via the bloodstream to the liver.
Stage 2 - Liver (Step 2)
Organ: Liver
Enzyme: Guanidinoacetate methyltransferase (GAMT)
Methyl donor: S-Adenosyl methionine (SAM), which becomes S-adenosylhomocysteine
Substrate: Guanidinoacetate
Product: Creatine
In the liver, guanidinoacetate is methylated by SAM to produce creatine. SAM is converted to S-adenosylhomocysteine in the process.
After Synthesis - Target Tissues
The creatine formed in the liver is released into the bloodstream and taken up by:
- Skeletal muscle (largest reservoir)
- Heart muscle
- Brain
In these tissues, creatine kinase (CK/CPK) phosphorylates creatine using ATP to form creatine phosphate, the high-energy storage form.
Diagram (from Lippincott's Illustrated Reviews - Biochemistry, 8th ed.)
Summary Table
| Stage | Organ | Enzyme | Reaction |
|---|
| 1 | Kidney | Amidinotransferase | Arginine + Glycine → Guanidinoacetate + Ornithine |
| 2 | Liver | Guanidinoacetate methyltransferase | Guanidinoacetate + SAM → Creatine + SAH |
| Use/storage | Muscle, heart, brain | Creatine kinase (CK) | Creatine + ATP → Creatine phosphate + ADP |
Key points:
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Three amino acids contribute atoms to creatine: arginine (guanidino group), glycine (the carbon backbone), and methionine (via SAM, the methyl group)
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Creatine and creatine phosphate spontaneously cyclize to form creatinine, which is excreted in urine and used clinically as a marker of renal function and muscle mass
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Creatine synthesis accounts for a large portion of SAM consumption in the body, making it relevant to one-carbon metabolism and homocysteine levels
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Basic Medical Biochemistry: A Clinical Approach, 6e, p. 1610
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Lippincott's Illustrated Reviews: Biochemistry, 8th ed., p. 812-813