As part of the heme biosynthetic pathway, catalyzes the sequential polymerization of four molecules of porphobilinogen to form hydroxymethylbilane, also known as preuroporphyrinogen (PubMed:18004775, PubMed:18936296, PubMed:19138865, PubMed:23815679). Catalysis begins with the assembly of the dipyrromethane cofactor by the apoenzyme from two molecules of porphobilinogen or from preuroporphyrinogen. The covalently linked cofactor acts as a primer, around which the tetrapyrrole product is assembled. In the last step of catalysis, the product, preuroporphyrinogen, is released, leaving the cofactor bound to the holodeaminase intact (PubMed:18936296).
Acute intermittent porphyria
AIP
A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AIP is an autosomal dominant form of hepatic porphyria characterized by attacks of gastrointestinal disturbances, abdominal colic, with neurological dysfunctions, hypertension, tachycardia and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors.
None
The disease is caused by variants affecting the gene represented in this entry.
Encephalopathy, porphyria-related
ENCEP
An autosomal recessive disorder characterized by rapidly progressive neurologic abnormalities apparent in early infancy. Clinical features include global developmental delay, impaired intellectual development, hypotonia, ataxia, dysarthria, spasticity, ocular abnormalities, and peripheral neuropathy. Laboratory studies show increased plasma and urinary levels of porphyrin precursors. Death in childhood may occur.
None
The disease is caused by variants affecting the gene represented in this entry.
Leukoencephalopathy, porphyria-related
LENCEP
An autosomal recessive disorder characterized by slowly progressive spasticity, ataxia, peripheral neuropathy, with or without mild cognitive impairment, and/or ocular disease with onset in childhood or adolescence.
None
The disease is caused by variants affecting the gene represented in this entry.
Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 2/4.
Belongs to the HMBS family.
Isoform 1
Is ubiquitously expressed.
Isoform 2
Is found only in erythroid cells.
PBGD, UPS, HMBS, Porphobilinogen deaminase, PBG-D, Hydroxymethylbilane synthase, Pre-uroporphyrinogen synthase
Proteins
Neuroscience
39330Da
We found 1 product in 1 category