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Pathway Description
Histidine Metabolism
Homo sapiens
Metabolic Pathway
Created: 2013-08-01
Last Updated: 2023-10-25
Histidine, an amino acid, plays an important role in the creation of proteins. It is unique as an amino acid as it is needed for 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 beginning compound for purine and pyrimidine creation. Subsequent histidine biosynthetic steps (from phosphoribosyl-ATP onwards) are likely to occur 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-forminino-AICAR-phosphate). This is subsequently converted to 5-phosphoribulosyl-forminino-5-aminoimidazole-4-carboxamide ribonucleotide. Cleavage of this compound creates imidazole glycerol phosphate and AICAR (aminoimidazolecarboxamide ribonucleotide) with glutamine being involved as an amino group donor. AICAR is used again through the purine pathway while the imidazole glycerol phosphate is converted to imidazole acetal phosphate. Transamination yields histidinol phosphate which is then turned into histidinol, and then, finally, to histidine. L-histidine is catalyzed by histidine ammonia-lyase into urocanic acid. This acid is then converted to 4-imidazolone-5-propionic acid by urocanate hydratase. 4-imidazolone-5-propionic acid is then converted to formiminoglutamic acid, using the enzyme probable imidazolonepropionase. One last reaction occurs to allow for glutamate metabolism, as formiminoglutamic acid is converted to l-glutamic acid through the use of formimidoyltransferase-cyclodeaminase. 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.
Histidine is found in meat, seeds, nuts and whole grains. It is a very important amino acid in keeping a pH of 7 in the body, as it acts as a shuttle for protons to maintain a balance of acids and bases in the blood and different tissues.
References
Histidine Metabolism References
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