histidase

Histidase, also known as histidine ammonia-lyase (HAL), is an enzyme that catalyzes the first step in the catabolism of the essential amino acid histidine. It cleaves histidine to produce urocanate and ammonia, a reaction that represents the entry point for histidine degradation in many organisms. In humans and other mammals, histidase activity is primarily found in the liver and to a lesser extent in the kidney and other tissues. The HAL gene encodes the enzyme in humans.

Biochemically, histidase initiates a pathway in which histidine is converted to urocanate, which is then processed by downstream enzymes such as urocanate hydratase and imidazolonepropionase. The pathway continues through intermediates including imidazolonepropionate and formiminoglutamate, ultimately contributing to the formation of glutamate and integration with one‑carbon metabolism. The histidine degradation pathway links amino acid catabolism to energy production and one‑carbon pool utilization.

Clinical significance of histidase relates to histidinemia, a metabolic condition arising from reduced or absent histidase activity. Histidinemia is typically autosomal recessive and is characterized by elevated histidine levels in blood and urine. Most individuals with histidase deficiency are asymptomatic, and the condition is often detected incidentally through newborn screening or laboratory testing.

Diagnosis relies on biochemical assessment of histidine levels in plasma and urine, measurement of HAL activity, or genetic testing for HAL mutations. In the absence of symptoms, management generally involves observation, with no specific dietary therapy required.