leucine
Summary
Leucine is a branched-chain amino acid (BCAA) that is nutritionally essential and purely ketogenic (does not contribute to gluconeogenesis). It plays a key role in muscle protein synthesis via mTOR pathway activation and is degraded via a distinct enzymatic pathway that, when deficient, causes Maple Syrup Urine Disease (MSUD).
Detail
Leucine, along with valine and isoleucine, is a branched-chain amino acid (BCAA). It is one of the nine essential amino acids and is unique among the BCAAs in being purely ketogenic—its metabolism yields acetoacetate and acetyl-CoA, with no glucogenic carbon skeleton contribution, unlike valine (glucogenic) and isoleucine (both keto- and glucogenic).
Metabolism: BCAAs (leucine, isoleucine, valine) undergo transamination by branched-chain aminotransferase to form their corresponding alpha-keto acids, which are then oxidatively decarboxylated by the branched-chain alpha-ketoacid dehydrogenase complex (BCKDH), a mitochondrial enzyme complex analogous to pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, requiring similar cofactors (thiamine/B1, lipoic acid, CoA, FAD, NAD+).
Clinical significance: Deficiency of BCKDH causes Maple Syrup Urine Disease (MSUD), an autosomal recessive inborn error of metabolism. Buildup of leucine, isoleucine, valine, and their alpha-keto acids leads to CNS toxicity, causing poor feeding, vomiting, lethargy, and a characteristic sweet,
Sources
- First Aid for the USMLE Step 1
- Lippincott Biochemistry
- Harper's Illustrated Biochemistry
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