Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.61 (porphobilinogen deaminase)
 637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new construct carrying the hemC gene was transformed into Escherichia coli, resulting in approx. 1000-fold over-expression of hydroxymethylbilane synthase (HMBS). This construct was used to generate HMBS in which (a) Lys-55, (b) Lys-59 and (c) both Lys-55 and Lys-59 were replaced by glutamine (K55Q, K59Q and K55Q-K59Q respectively). All three modified enzymes are chromatographically separable from wild-type enzyme. Kinetic studies showed that the substitution K55Q has little effect whereas K59Q causes a 25-fold decrease in Kapp. cat./Kapp. m. Treatment of K55Q, K59Q and K55Q-K59Q separately with pyridoxal 5'-phosphate and NaBH4 resulted in incomplete and non-specific reaction with the remaining lysine residues. Pyridoxal modification of Lys-59 in the K55Q mutant caused greater enzymic inactivation than similar modification of Lys-55 in K59Q. The results in sum show that, though Lys-55 and Lys-59 may be at or near the active site, neither is indispensable for the catalytic activity of HMBS.
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PMID:Investigation of putative active-site lysine residues in hydroxymethylbilane synthase. Preparation and characterization of mutants in which (a) Lys-55, (b) Lys-59 and (c) both Lys-55 and Lys-59 have been replaced by glutamine. 212 89

Acute intermittent porphyria (AIP) is an autosomal dominant disease caused by mutations of the gene coding for hydroxymethylbilane synthase. Acute attack of AIP is a potentially life-threatening condition precipitated by certain drugs, alcohol, fasting and stress. Biochemical diagnosis before the manifestation of the symptoms is problematic, and genetic screening is required to identify asymptotic carriers. The aim of this study was to establish a fast, reproducible and reliable genetic method to detect mutations causing AIP. Exon 10 of one healthy individual and 12 AIP patients was studied using a recently developed method, temporal temperature gradient electrophoresis (TTGE). Mutation of exon 10 was detected using TTGE in one patient, DNA sequence analysis confirmed the presence of a heterozygous point mutation causing substitution of the arginine in position 173 of the gene with glutamine. These results were also confirmed using restriction enzyme analysis, and this method and TTGE identified a child of this patient as an asymptotic carrier of AIP.
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PMID:Identification of acute intermittent porphyria carriers by molecular biologic methods. 1074 73

Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a partial deficiency of porphobilinogen deaminase (PBGD), the third enzyme in the of heme biosynthetic pathway. It can affect the autonomic, peripheral, and central nervous system. Posterior reversible encephalopathy syndrome is a clinicoradiological entity characterized by headache, seizures, altered consciousness, and visual disorder associated with potentially reversible neuroradiological abnormalities predominantly in the parieto-occipital lobes. Establishing accurate diagnoses of the patient and asymptomatic family members with AIP involves identifying the PBGD enzyme mutations directly. In this study, we report a 28-year-old woman with acute intermittent porphyria who presented with radiological manifestations suggestive of posterior reversible encephalopathy syndrome, she had a novel PBGD frame shift mutation, base 875 and 876 have been deleted resulting in glutamine to a stop codon (Gln292fs), in a Chinese family.
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PMID:Reversible MRI findings in a case of acute intermittent porphyria with a novel mutation in the porphobilinogen deaminase gene. 2801 90