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)

Alterations in heme biosynthetic and degradative capabilities and in the activities of several heme-containing enzymes were examined in hepatic tissues of streptozotocin (STZ)-diabetic female Sprague-Dawley rats. Activities were measured 10, 30 and 90 days following the administration of STZ (65 mg/kg, i.v.). The activities of the key enzymes involved in heme synthesis, delta-aminolevulinic acid (ALA) synthase, ALA dehydratase, and uroporphyrinogen synthase, were decreased markedly in STZ-diabetic rats as compared to sham-operated animals. Furthermore, the catabolism of heme which occurs via microsomal heme oxygenase (MHO) remained unaltered in these animals. Microsomal content of heme and cytochrome P-450, and the activities of tryptophan pyrrolase and the drug-metabolizing enzymes benzo[a]pyrene (BP) hydroxylase and aniline hydroxylase, were increased in the livers of diabetic rats. By contrast, the activity of the heme-containing enzyme catalase was decreased in these animals. Cobalt chloride produced a marked increase in MHO with a concomitant decrease in microsomal content of cytochrome P-450 and its associated BP hydroxylase activity in normal as well as chronically diabetic rats. It was of interest, however, that the increase in ALA synthase that is normally produced by this metal was not seen in chronic diabetic animals. Thus, chronic diabetes produced subtle and important disruptions in cellular metabolism, which may have been the result of long-term alterations in key enzymes involved in heme synthesis.
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PMID:Heme and hemoproteins in streptozotocin-diabetic female rats. 668 50

Acute intermittent porphyria (AIP) is a hereditary disease characterized biochemically by a defect in the heme pathway enzyme porphobilinogen deaminase. There is wide variability in the neurologic clinical expression of AIP, and the disorder remains latent in most gene carriers. The natural history of the disease and results in a porphyric rat model suggest a significant relationship between tryptophan metabolites and clinical expression of the disease. In the present study, we examined urine and blood tryptophan metabolite levels in AIP women before, during and after acute attacks and treatment by heme arginate. Heme arginate treatment promptly decreased total tryptophan levels (from 69 +/- 9, to 44 +/- 5, mean +/- SEM, mumole/l, p < 0.001), serotonin blood levels (from 629 +/- 103, to 356 +/- 80, nmole/l, p < 0.01) and the urinary excretion of 5-HIAA (from 3.9 +/- 0.6, to 2.2 +/- 0.4, mumole/mmole creatinine, p < 0.01). The plasma level of melatonin was found much lower than the normal control level at night (86.2 +/- 70.3, vs the normal range, 409 +/- 78.9, pmole/l +/- SEM) and day time (38.8 +/- 22.0, vs 75 +/- 13.7). Heme arginate treatment did not influence melatonin levels. Our results support the involvement of abnormal tryptophan metabolism in the pathophysiology of AIP acute attacks. Low melatonin plasma levels in porphyric women suggest that the defect of the pineal hormone may be responsible for the recurrent aspect of porphyric attacks. A desynchronization of biological rhythms in AIP patients may increase the inducibility of hepatic ALA synthase to environmental risk factors and, specially, to sex steroid hormones.
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PMID:Decreased nocturnal plasma melatonin levels in patients with recurrent acute intermittent porphyria attacks. 835 Jun 77

Acute intermittent porphyria (AIP) is an inherited disorder characterized by a deficiency of hydroxymethylbilane synthase (EC 4.3.1.8.; HMBS), the third enzyme in the heme biosynthetic pathway. To date, 113 different HMBS gene mutations have been reported in the world. However, there were a few reports of the gene mutations in the Japanese AIP patients. We studied the gene mutation in two unrelated AIP families in the San-in district, a local area of Western Japan. The overlapping 6 fragments of the HMBS gene, amplified by the reverse transcript-polymerase chain reaction, were analyzed by the single-strand conformation polymorphism with silver staining technique. The abnormal fragment from a member of one family was sequenced to detect the C to T substitution at 517 nucleic acid position of cDNA, which led to a missense mutation of arginine to tryptophan exchange at an amino acid level (R173W). This mutation located in exon 10 created a new site of the MSP 1 restriction endonuclease and was screened by the amplified fragment of exon 10 from genomic DNA with the MSP 1 digestion. The mutation was detected totally in three members of the family and interestingly also in two patients of an unrelated family. This mutation has been reported widely in the world independently, such as in a Swedish, a Canadian, a Finnish, and a French family, but is the first in Japanese patients. The screening method for this mutation is useful for diagnosis in Japanese AIP patients.
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PMID:Mutation in the exon 10 (R173W) of the hydroxymethylbilane synthase gene in two unrelated Japanese families with acute intermittent porphyria. 952 50