Histidine ammonia-lyase (EC4.3.1.3, histidase, histidinase) is an enzyme that in humans is encoded by the HALgene.[5][6] It converts histidine into ammonia and urocanic acid. Its systematic name is L-histidine ammonia-lyase (urocanate-forming).
Histidine ammonia-lyase is a cytosolic enzyme catalyzing the first reaction in histidine catabolism, the nonoxidative deamination of L-histidine to trans-urocanic acid.[5] The reaction is catalyzed by 3,5-dihydro-5-methyldiene-4H-imidazol-4-one (MIO), an electrophilic cofactor which is formed autocatalytically by cyclization of the protein backbone of the enzyme.[7]
Proposed autocatalytic formation of MIO cofactor in another enzyme, phenylalanine ammonia-lyase, from the tripeptide Ala-Ser-Gly by two water elimination steps.
^Suchi M, Sano H, Mizuno H, Wada Y (September 1995). "Molecular cloning and structural characterization of the human histidase gene (HAL)". Genomics. 29 (1): 98–104. doi:10.1006/geno.1995.1219. PMID8530107.
^Schwede T, Rétey J, Schulz G (Apr 27, 1999). "Crystal structure of histidine ammonia-lyase revealing a novel polypeptide modification as the catalytic electrophile". Biochemistry. 38 (17): 5355–5361. doi:10.1021/bi982929q. PMID10220322.
Suchi M, Harada N, Wada Y, Takagi Y (Nov 1993). "Molecular cloning of a cDNA encoding human histidase". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1216 (2): 293–295. doi:10.1016/0167-4781(93)90157-9. PMID7916645.
Davila S, Froeling FE, Tan A, Bonnard C, Boland GJ, Snippe H, et al. (Apr 2010). "New genetic associations detected in a host response study to hepatitis B vaccine". Genes and Immunity. 11 (3): 232–238. doi:10.1038/gene.2010.1. PMID20237496. S2CID11183658.
Eckhart L, Schmidt M, Mildner M, Mlitz V, Abtin A, Ballaun C, et al. (Jun 2008). "Histidase expression in human epidermal keratinocytes: regulation by differentiation status and all-trans retinoic acid". Journal of Dermatological Science. 50 (3): 209–215. doi:10.1016/j.jdermsci.2007.12.009. PMID18280705.
Kawai Y, Moriyama A, Asai K, Coleman-Campbell CM, Sumi S, Morishita H, et al. (Apr 2005). "Molecular characterization of histidinemia: identification of four missense mutations in the histidase gene". Human Genetics. 116 (5): 340–346. doi:10.1007/s00439-004-1232-5. PMID15806399. S2CID33960184.
Taylor RG, Garcia-Heras J, Sadler SJ, Lafreniere RG, Willard HF, Ledbetter DH, et al. (1991). "Localization of histidase to human chromosome region 12q22→q24.1 and mouse chromosome region 10C2→D1". Cytogenetics and Cell Genetics. 56 (3–4): 178–181. doi:10.1159/000133082. PMID2055114.
Aleman G, Ortiz V, Langley E, Tovar AR, Torres N (Jul 2005). "Regulation by glucagon of the rat histidase gene promoter in cultured rat hepatocytes and human hepatoblastoma cells". American Journal of Physiology. Endocrinology and Metabolism. 289 (1): E172 –E179. doi:10.1152/ajpendo.00584.2004. PMID15741241.
