Histidine

Histidine is an essential amino acid used to synthesize proteins. It is one of the 20 standard amino acids and exists in two stereoisomers, with the L-enantiomer incorporated into proteins. The side chain of histidine is an imidazole ring, which has a pKa near 6.0. This makes the imidazole group capable of switching between protonated and unprotonated forms near physiological pH, enabling versatile roles in catalysis and metal binding.

Biological roles of histidine include participation of histidine residues in acid–base reactions, acting as proton donors and acceptors, and coordinating metal ions in enzymes. Its ability to buffer near pH 7.4 and stabilize transition states contributes to catalysis in many proteins. Histidine is considered essential in the human diet, particularly important for growth in infants.

Nutrition and metabolism: Humans cannot synthesize histidine and must obtain it from the diet. Rich sources include meat, fish, eggs, dairy products, legumes, and certain grains. In addition to protein incorporation, histidine is decarboxylated to histamine, a neurotransmitter and inflammatory mediator. Histidine is degraded by histidine ammonia-lyase to urocanate, with subsequent steps feeding into glutamate production and related metabolic pathways.

Clinical and research notes: As an essential amino acid, histidine intake is necessary for health and development. Beyond nutrition, histidine residues are used in protein engineering and purification workflows, where polyhistidine tags aid in affinity purification systems.