Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

Official Name

hydroxymethylbilane synthase

Name from literature

uroporphyrinogen synthase

Pathway from literature

porphyrin synthesis

Pathway from KEGG

Metabolism of Cofactors and Vitamins; Porphyrin and chlorophyll metabolism; map00860


Human (9606)

Genome localization

11q23.3[3145 ],


The enzyme works by stepwise addition of pyrrolylmethyl groups until a hexapyrrole is present at the active centre. The terminal tetrapyrrole is then hydrolysed to yield the product, leaving a cysteine-bound dipyrrole on which assembly continues. In the presence of a second enzyme, EC uroporphyrinogen-III synthase, which is often called cosynthase, the product is cyclized to form uroporphyrinogen-III. If EC is absent, the hydroxymethylbilane cyclizes spontaneously to form uroporphyrinogen I.

Rate-limiting Description

"The observations may be explained by the known pH-dependency of the activity of porphobilinogen deaminase (PBGD) and are in agreement with the assumption that PBGD constitutes a rate-limiting step in the synthesis of PpIX from ALA." (9065797)

"The latter activation energy was within the error limits similar to that for the activity of the enzyme porphobilinogen deaminase, suggesting that this enzyme might represent a rate-limiting step for PpIX production in living tissue." (10546563)

"Two mechanisms may explain the results: enhancement of the efficiency of the rate-limiting enzyme porphobilinogen deaminase by folic acid or interference of folic acid with the transport of ALA and MAL to and into the cells synthesizing porphyrins in the tissues." (16886091)

"All cases of acute intermittent porphyria (AIP) are believed to be caused by a mutation in the gene encoding for porphobilinogen deaminase, a rate-limiting enzyme in the haem synthetic pathway." (8023693)

"Ethanol suppresses the activity of porphobilinogen synthase (synonym: delta-aminolevulinic acid dehydratase), uroporphyrinogen decarboxylase, coproporphyrinogen oxidase and ferrochelatase, whereas it induces the first and rate-limiting enzyme in the pathway, delta-aminolevulinic acid synthase and also porphobilinogen deaminase." (10787385)

"In the present study we focused on the role of the rate-limiting enzyme porphobilinogen deaminase in glioma C6 cell activity, differentiation and sub-cellular distribution." (11953837)

"These observations of an associated response of PBGD and PPIX imply that PBGD may be a rate-limiting determinant for the efficacy of delta-ALA-induced photosensitization when used in photodynamic therapy." (9460994)

"The conversion of exogenous ALA into porphyrins decreases with increasing concentrations of ALA from 0.1 to 2.0 mmol/l, whereas porphobilinogen accumulates, thus reflecting the rate limiting function of uroporphyrinogen synthase, which is not influenced by glucose." (4067519)

Regulatory Information

Upstream transcription factor


Regulatory type



"the PBGD cellular pool is controlled by the proteasome activity, which in turn is down regulated by hemin or up-regulated by Pb-ALAD." (16935474)

transcriptional factor;GATA-1(2623),NFE-2 erythroid-specific transcription factor(8328)

"Using the electrophoretic mobility shift assay, during differentiation over 3 days of culture, we have observed an increase in the binding either of GATA-1 to the promoter of the gamma-globin gene (region -201 to -156) or NFE-2 to the promotor of the porphobilinogen deaminase gene (region -170 to -142). " (2251113#8445949)

Gene ontology

Gene ontology

GO:0004418 (F) hydroxymethylbilane synthase activity [P08397 ];
GO:0006783 (P) heme biosynthetic process [P08397 ];
GO:0005739 (C) mitochondrion [P08397 ];

Tissue expression

Tissue From HPRD

Liver [01440 ];
Red blood cell [01440 ];
Spleen [01440 ];

Tissue specificity

Isoform 1 is ubiquitously expressed, isoform 2 is found only in erythroid cells [P08397 ];

Subcellular localization


cytoplasm [P08397 ];

Disease relevance


Defects in HMBS are the cause of acute intermittent porphyria (AIP) [MIM:176000]. AIP is 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 acute attacks of neurological dysfunctions with abdominal pain, hypertension, tachycardia, and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors [P08397 ];




Entrez Gene




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  Last Modified: 2009-03-24  
  Design by Zhao Min