Histidine

Route: 5-Phosphoribosyl 1-pyrophosphate → Phosphoribosyl-ATP → Phosphoribosyl-AMP → ProFAR → PRFAR → Imidazole glycerol phosphate → Imidazole acetol phosphate → L-Histidinol phosphate → L-Histidinol → L-Histidinal → Histidine

Humans cannot make histidine, so it is an essential amino acid that must come from food. Bacteria, fungi and plants use this route. It starts by joining ATP to PRPP, which gives phosphoribosyl-ATP. The next two steps remove the diphosphate and open the purine ring, which gives ProFAR. An isomerase turns the ribose of one half into a ribulose. The glutamine amidotransferase then splits the molecule: one half becomes imidazole glycerol phosphate, and the other half is AICAR, which goes on into purine synthesis. Dehydration, transamination from glutamate and dephosphorylation make histidinol. Histidinol dehydrogenase oxidizes it twice, first to the aldehyde and then to the acid, and uses two NAD⁺. In E. coli one protein does two jobs: HisI and HisE are fused (steps 2 and 3), and HisB catalyzes both the dehydration and the dephosphorylation. Each fused enzyme is shown at each step it catalyzes. Ammonia from glutamine travels through a tunnel across the barrel of the imidazole glycerol phosphate synthase complex. The pathway here is the shortened teaching version: cofactors such as Mg²⁺, Zn²⁺ and pyridoxal phosphate are not drawn.

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Steps

Enzyme names and EC numbers are those used on the interactive board. Checked against sources: see the claim table in the repository (tools/pathway_data/checks).