Porphobilinogen deaminase

This enzyme is also called porphobilinogen deaminase or hydroxymethylbilane synthase. 

Finke et al.54 BJAB cells (B-lymphocytic cell line) 1% SDS + proteinase K Housekeeping gene PBGD (porphobilinogen deaminase) Most routine FFPE tissues will be available for RNA analysis. 

Acute intermittent porphyria is a dominantly inherited partial deficiency of porphobilinogen deaminase, and causes axonal polyneuropathy. Acute intermittent porphyria is caused by partial deficiency of porphobilinogen deaminase, an enzyme required for heme biosynthesis. Patients may present with acute abdominal pain, rapidly progressive sensorimotor axonal polyneuropathy or psychosis, and have elevated concentrations of the heme precursor 8-amino-levulinic acid in their urine. Symptoms may be precipitated by treatment with barbiturates or other drugs and are suppressed by treatment with hematin [59]. 

Floderus, Y., Shoolingin-Jordan, R M. and Harper, P. Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene. Clin. Genet. 62 288-297, 2002. 

Schuurmans MM, Schneider-Yin X, Rufenacht UB, Schnyder C, Minder CE, Puy H, Dey-bach JC, Minder El (2001) Influence of age and gender on the clinical expression of acute intermittent porphyria based on molecular study of porphobilinogen deaminase gene among Swiss patients. Mol Med 7 535-542... 

The formation of uroporphyrinogen III from PBG in vivo requires the participation of two enzymes, porphobilinogen deaminase and uroporphyrinogen III cosynthetase. In the presence of the first enzyme alone, (65) is converted into uroporphyrinogen I which does not act as a substrate for the second enzyme. The formation of uroporphyrinogen I must... 

In 1992 the X-ray crystal structure of porphobilinogen deaminase was solved, an enzyme that is involved with the biosynthesis of a linear tetrapyrrole precursor to protoporphyrin IX, found in haemoglobin... 

Figure 4.7 (a) interaction of a dipyrromethane-based cofactor in porphobilinogen deaminase with... 

Louie, G. V., Brownlie, P. D., Lambert, R., etal, Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site. Nature 1992, 359, 33-39. 

Acute intermittent porphyria is a severe form of porphyria which is due to a deficiency of porphobilinogen deaminase (hydroxymethylbilanesynthase). 

Figure 3 The synthesis of heme from glycine and sucdnyl-CoA. The enzymes are ALAS, S-aminolevulinic acid (ALA) synthase ALAD, S-aminolevulinic acid dehydratase PBGD, porphobilinogen deaminase UROIIIS, uroporphyrinogen III synthase UROD, uroporphyrinogen decarboxylase CPO, coproporphyrinogen oxidase PPO, protoporphyrinogen oxidase and FECH, ferrochelatase.

Nordmann Y, Puy H, Da Sfiva V, Simonin S, Robreau AM, Bonaiti C, et al. Acute intermittent porphyria prevalence of mutations in the porphobilinogen deaminase gene in blood donors in France. J Intern Med 1997 242 213-7. 

Schreiber WE, Rozon C> Fong F, Jamani A. Detection of polymorphisms and mutations in the porphobilinogen deaminase gene by nonisotopic SSCP. 

Shoolingin-Jordan PM, Warren MJ, Awan SJ. Dipyrroraethane cofactor assembly of porphobilinogen deaminase formation of apoenzyme and preparation of holoenzyme. Methods Enzymol 1997 281 327-36. 

Acute intermittent porphyria is associated with excessive urinary excretion of ALA and porphobilinogen. The lack of polymerization of porphobilinogen is due to deficiency of porphobilinogen deaminase in several cell types (e.g., hepatocytes, erythrocytes, fibroblasts, lymphocytes). Acute clinical manifestations include neuropsychiatric disorders and abdominal pain. The cause of these manifestations is not clear, but accumulation of porphyrin precursors (ALA and porphobilinogen) in pharmacological amounts has been implicated. Since afflicted subjects cannot make porphyrins to any great extent, they are not photosensitive. This disorder is inherited as an autosomal dominant trait. 

Lambert R, Brownlie PD, Woodcock SC, Louie GV, Cooper JC, Warren MJ, Jordan PM, Blundell TL, Wood SP (1994) Structural studies on porphobilinogen deaminase. In The biosynthesis of the tetrapyrrole pigments. Ciba Foundation Symposium, vol 180. WUey, Chichester, p 97... 

Leeper, F.J., and Rock, M., Modified substrates for tetrapyrrole biosynthesis. Analogues of porphobilinogen showing unusual inhibition of porphobilinogen deaminase, 7. Chem. Soc., Chem. Commun., 242, 1992. 

Porphobilinogen deaminase (PBGD) Cytosolic enzyme that processes six PEG molecules through a hexapyrrole adduct to catalyze the formation of a free linear tetrapyrrole, hydroxymethylbilane (aka uroporphyrinogen I synthase). 

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