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Pathway · 6 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
Imidazoleglycerol-phosphate dehydratase4.2.1.19D-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 isomerase5.3.1.161-(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 HisF4.3.2.105-[(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 HisIE3.5.4.19; 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 HisH3.5.1.2; 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 dehydrogenase1.1.1.23L-histidinol + 2 NAD(+) + H2O = L-histidine + 2 NADH + 3 H(+)Zn(2+)426Step 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 the twenty amino acids.

Sources

Other pathways in this group: Aromatic amino acids · Branched-chain amino acids · Aspartate-family branches · Nitrogen assimilation · RNA maturation · Folate-linked carbon transfer · Arginine biosynthesis · Cysteine and methionine metabolism · Lysine biosynthesis · Arginine and proline metabolism · Phenylalanine, tyrosine and tryptophan biosynthesis · Not yet placed in a pathway