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)

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

Our objective was to evaluate the activities of some enzymes of the heme biosynthesis pathway and their relationship with the profile of urinary porphyrin excretion in individuals exposed chronically to arsenic (As) via drinking water in Region Lagunera, Mexico. We selected 17 individuals from each village studied: Benito Juarez, which has current exposure to 0.3 mg As/l; Santa Ana, where individuals have been exposed for more than 35 years to 0.4 mg As/l, but due to changes in the water supply (in 1992) exposure was reduced to its current level (0.1 mg As/l), and Nazareno, with 0.014 mg As/l. Average arsenic concentrations in urine were 2058, 398, and 88 microg As/g creatinine, respectively. The more evident alterations in heme metabolism observed in the highly exposed individuals were: (1) small but significant increases in porphobilinogen deaminase (PBG-D) and uroporphyrinogen decarboxylase (URO-D) activities in peripheral blood erythrocytes; (2) increases in the urinary excretion of total porphyrins, mainly due to coproporphyrin III (COPROIII) and uroporphyrin III (UROIII); and (3) increases in the COPRO/URO and COPROIII/COPROI ratios. No significant changes were observed in uroporphyrinogen III synthetase (UROIII-S) activity. The direct relationships between enzyme activities and urinary porphyrins, suggest that the increased porphyrin excretion was related to PBG-D, whereas the increased URO-D activity would enhance coproporphyrin synthesis and excretion at the expense of uroporphyrin. None of the human studies available have reported the marked porphyric response and enzyme inhibition observed in rodents. In conclusion, chronic As exposure alters human heme metabolism; however the severity of the effects appears to depend on characteristics of exposure not yet fully characterized.
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PMID:Altered activity of heme biosynthesis pathway enzymes in individuals chronically exposed to arsenic in Mexico. 1035 Jan 89