描述
Histidine is unique in that its biosynthesis is inherently linked to the pathways of nucleotide formation. The biosynthesis of histidine in adults begins with the condensation of ATP and PRPP (phosphoribosyl pyrophosphate) to form N-5-phosphoribosyl 1-pyrophosphate (phosphoribosyl-ATP). It is also worth noting that PRPP is the starting point for purine and pyrimidine biosynthesis. Subsequent histidine biosynthetic steps (from phosphoribosyl-ATP onwards) likely take place in the intestinal microflora. Elimination of the phosphate and the opening of the ring in phosphoribosyl-ATP forms phosphoribosyl-forminino-5-aminoimidazole-4-carboxamide ribonucleotide (phosphoribosyl-formimino-AICAR-phosphate). This is subsequently converted to 5-phosphoribulosyl-forminino-5-aminoimidazole-4-carboxamide ribonucleotide. Cleavage of this intermediate results in the formation of imidazole glyercol phosphate and AICAR (aminoimidazolecarboxamide ribonucleotide) with glutamine playing a role as an amino group donor. AICAR is recycled through the purine pathway while the imidazole glycerol phosphate is converted to imidazole acetal phosphate. Transamination yields histidinol phosphate which is converted to histidinol and finally to histidine. Histidine catabolism begins with release of the α-amino group catalyzed by histidase, leading to the deaminated product, urocanate. Urocanate is converted to 4-imidazolone-5-propionate via the action of urocanate hydratase. The latter product is then converted to N-formiminoglutamte via the action of imidazolone propionase. The enzyme formiminotransferase cyclodeaminase then removes the formimino group to yield glutamate. Because the end product of histidine catabolism is glutamate this makes histidine one of the glucogenic amino acids. Another key feature of histidine catabolism is that it serves as a source of ring nitrogen to combine with tetrahydrofolate (THF), producing the 1-carbon THF intermediate known as N5-formiminoTHF. The latter reaction is one of two routes to N5-formiminoTHF. Decarboxylation of histidine in the intestine by bacteria gives rise to histamine. Similarly, histamine arises in many tissues by the decarboxylation of histidine, which in excess causes constriction or dilation of various blood vessels. Once histamine is generated it can be converted to several breakdown products including N-methylhistamine, imidazole acetaldehyde, methylimidazole acetaldehyde and methylimidazole-acetic acid. Histidine is also a precursor for carnosine biosynthesis (via carnosine synthase), with beta-alanine being the rate limiting precursor. Anserine can be synthesized either from carnosine via carnosine N-methyltransferase or from 1-methylhistidine via carnosine synthase. Inversely, cytosolic non-specific dipeptidase catalyzes the synthesis of 1-methylhistidine from anserine.