leucines

Leucines are essential amino acids of the branched-chain family. In proteins, the naturally occurring form is L-leucine; D-leucine is rare and not used in ribosomal protein synthesis. Leucine is a nonpolar, aliphatic amino acid with an isobutyl side chain and is one of the most abundant branched-chain amino acids in dietary proteins.

Chemically, leucine is known as 2-amino-4-methylpentanoic acid. It is predominantly found as the L-enantiomer in proteins. Leucine’s hydrophobic side chain contributes to protein structure and folding and makes it relatively resistant to enzymatic degradation unless processed by specific catabolic enzymes.

Biologically, leucine is essential for humans, meaning it must be obtained through the diet. It plays a central role in protein synthesis, partly by activating the mTORC1 signaling pathway, which promotes translation and muscle protein synthesis, especially after exercise. Leucine also serves as an energy source during prolonged fasting or energy stress through its catabolism.

Metabolism and biosynthesis: In humans, leucine is degraded via the branched-chain amino acid catabolic pathway. It undergoes transamination by branched-chain aminotransferase to form α-ketoisocaproate, which is further processed by branched-chain α-keto acid dehydrogenase. The final products are acetyl-CoA and acetoacetate, making leucine strictly ketogenic (not glucogenic). In microorganisms and plants, leucine can be synthesized from pyruvate through a dedicated set of enzymes in the isopropylmalate pathway.

Dietary sources and clinical notes: Leucine is abundant in animal proteins and in many plant proteins. Deficiency is rare but can occur with severe protein malnutrition. A metabolic disorder, maple syrup urine disease, results from defects in BCAA catabolism, leading to elevated leucine levels and neurotoxicity if untreated.