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Pathway · 2 proteins

Histidine metabolism

Proteins of this group that KEGG places on its “Histidine metabolism” map for Aquifex aeolicus.

How it works

This map shows the ten-step synthesis of histidine from PRPP and ATP. The proteins here run the whole route, from the first enzyme (ATP phosphoribosyltransferase, with its regulatory partner) through ring closure by imidazole glycerol phosphate synthase to histidinol dehydrogenase, which makes histidine.

Grouped by KEGG pathway map. The explanation above is the atlas’s own; the map itself covers more organisms than Aquifex.

Its proteins

ProteinECReaction (UniProt)Metal or clusterAmino acidsCertainty
ATP phosphoribosyltransferase regulatory subunit———383Step named
ATP phosphoribosyltransferase2.4.2.171-(5-phospho-beta-D-ribosyl)-ATP + diphosphate = 5-phospho-alpha-D-ribose 1-diphosphate + ATP—214Step named

Also part of this pathway

These proteins are described under another pathway, but also take part here.

ProteinECReaction (UniProt)Metal or clusterAmino acidsCertainty
Imidazoleglycerol-phosphate dehydrataseHome: Histidine metabolism4.2.1.19D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate = 3-(imidazol-4-yl)-2-oxopropyl phosphate + H2O—192Step named
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino] imidazole-4-carboxamide isomeraseHome: Histidine metabolism5.3.1.161-(5-phospho-beta-D-ribosyl)-5-[(5-phospho-beta-D-ribosylamino)methylideneamino]imidazole-4-carboxamide = 5-[(5-phospho-1-deoxy-D-ribulos-1-ylimino)methylamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide—238Step named
Imidazole glycerol phosphate synthase subunit HisFHome: Histidine metabolism4.3.2.105-[(5-phospho-1-deoxy-D-ribulos-1-ylimino)methylamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide + L-glutamine = D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate + 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide + L-glutamate + H(+)—253Step named
Histidine biosynthesis bifunctional protein HisIEHome: Histidine metabolism3.5.4.19; 3.6.1.311-(5-phospho-beta-D-ribosyl)-ATP + H2O = 1-(5-phospho-beta-D-ribosyl)-5'-AMP + diphosphate + H(+)—205Step named
Imidazole glycerol phosphate synthase subunit HisHHome: Histidine metabolism3.5.1.2; 4.3.2.105-[(5-phospho-1-deoxy-D-ribulos-1-ylimino)methylamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide + L-glutamine = D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate + 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide + L-glutamate + H(+)—207Step named
Histidinol dehydrogenaseHome: Histidine metabolism1.1.1.23L-histidinol + 2 NAD(+) + H2O = L-histidine + 2 NADH + 3 H(+)Zn(2+)426Step named
Histidinol-phosphate aminotransferaseHome: Not yet placed in a pathway2.6.1.9L-histidinol phosphate + 2-oxoglutarate = 3-(imidazol-4-yl)-2-oxopropyl phosphate + L-glutamate—354Step named

Origins

Could histidine, with its imidazole ring, have been available before this pathway existed?

Naturalistic proposal

Histidine has not been convincingly made under simulated prebiotic conditions, and Cairns-Smith counts it among the amino acids that lack any plausible prebiotic route.

Design analysis

The cell builds histidine in ten steps. One enzyme, imidazole glycerol phosphate synthase, passes ammonia through an internal tunnel from one active site to the other.

Histidine is also at the heart of many enzymes' active sites, so making it already needs working enzymes.

From the books: Garrett & Grisham, Biochemistry, pp. 665 and 912; Cairns-Smith, Genetic Takeover and the Mineral Origins of Life, p. 22.

The wider question for this part of the cell: origins for making dna and rna letters.

Sources

Other pathways in this group: Purine biosynthesis · Pyrimidine biosynthesis · Interconversion and salvage · Deoxyribonucleotide supply · Aromatic amino acids · Purine metabolism · Pyrimidine metabolism · Not yet placed in a pathway