Which organs are involved in the successive stages of creatine synthesis

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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.)

Creatine synthesis pathway showing kidney and liver steps

Summary Table

StageOrganEnzymeReaction
1KidneyAmidinotransferaseArginine + Glycine → Guanidinoacetate + Ornithine
2LiverGuanidinoacetate methyltransferaseGuanidinoacetate + SAM → Creatine + SAH
Use/storageMuscle, heart, brainCreatine kinase (CK)Creatine + ATP → Creatine phosphate + ADP

Key points:
  • Three amino acids contribute atoms to creatine: arginine (guanidino group), glycine (the carbon backbone), and methionine (via SAM, the methyl group)
  • 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
  • Creatine synthesis accounts for a large portion of SAM consumption in the body, making it relevant to one-carbon metabolism and homocysteine levels
  • Basic Medical Biochemistry: A Clinical Approach, 6e, p. 1610
  • Lippincott's Illustrated Reviews: Biochemistry, 8th ed., p. 812-813
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