Metabolism of Arginine
- Arginine is a semi-essential amino acid.
- Adults synthesize some via the urea cycle, but growing children need more from diet.
- Major sources of Arginine in the body:
- Dietary proteins
- Endogenous synthesis from Ornithine and Citrulline (urea cycle)
- Main metabolic roles of Arginine:
- Protein synthesis
- Precursor of Nitric Oxide (NO)
- Precursor of Creatine
- Precursor of Polyamines
- Short-term substrate for urea formation (removal of ammonia)
Synthesis of Nitric Oxide (NO) from Arginine
- Reaction:
- Arginine → Citrulline + NO
- Enzyme: Nitric Oxide Synthase (NOS)
Types:
- eNOS (endothelial, vasodilation)
- nNOS (neuronal, neurotransmission)
- iNOS (immune cells, strong NO burst for killing pathogens)
- Cofactors: NADPH, FAD, FMN, BH4.
- Function of NO:
- Vasodilation by activating cGMP in vascular smooth muscle.
- Neurotransmission in brain.
- Macrophage-mediated microbe killing (iNOS).
- Clinical association:
- Nitroglycerin donates NO → treats angina by increasing coronary blood flow.
- Hypertension and endothelial dysfunction → reduced NO.
Synthesis of Creatine
Creatine is used to store high-energy phosphate in muscle and brain.
- Pathway:
- Arginine + Glycine → Guanidinoacetate (in kidney)
- Guanidinoacetate → Creatine (in liver) using SAM (S-adenosylmethionine)
- Creatine → Creatine phosphate (Phosphocreatine) in muscle
- Acts as rapid ATP buffer during intense activity (first seconds of sprint).
- Spontaneous non-enzymatic breakdown:
- Creatine → Creatinine (excreted in urine)
- Creatinine clearance is a clinical indicator of kidney function.