Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.5.1.4 (deaminase)
5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors screened 3,867 psychiatric inpatients for intermittent acute porphyria by use of a spot test to detect diminished activity of the erythrocyte enzyme porphobilinogen (PBG) deaminase. Eighteen individuals so identified also had persistently diminished quantitative activity of PBG deaminase. Eight of these appeared to have intermittent acute porphyria by the added criteria of increased urinary delta-aminolevulinic acid or PBG or a family history of intermittent acute porphyria. The overall prevalence of intermittent acute porphyria was 0.21%, a considerably higher rate than that in the general population. Most of the subjects with the disorder had periods of agitated psychosis and apathetic or depressed withdrawal, with signs of neuropsychological impairment. Neurologic abnormalities were not prevalent.
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PMID:High prevalence of intermittent acute porphyria in a psychiatric patient population. 407 6

A frequent coexistence of diabetes and porphyria disease has been reported. Under normal conditions, porphyrin biosynthesis is well regulated to only form the amount of heme required for the synthesis of the various hemoproteins. The activity of some heme enzymes and rhodanese in streptozotocin (STZ) induced diabetic mice and in allylisopropylacetamide (AIA) induced experimental acute porphyria mice has been examined. The role of alpha-tocopherol (alpha-T), reported to prevent protein glycation in vitro, has also been investigated. AIA induced hepatic delta-aminolevulinic acid synthetase (ALA-S) activity in control animals but was ineffective in the diabetic group. alpha-Tocopherol did not modify ALA-S activity in either group. delta-Aminolevulinic acid dehydratase (ALA-D) and deaminase activities were significantly diminished both in liver and blood of diabetic animals. alpha-Tocopherol prevented inhibition of ALA-D, deaminase and blood rhodanese activities in diabetic animals but alpha-tocopherol by itself did not affect the basal levels of the enzymes studied. The potential use of alpha-tocopherol to prevent late complications of diabetes, including the onset of a porphyria like syndrome is considered.
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PMID:STZ-induced diabetes in mice and heme pathway enzymes. Effect of allylisopropylacetamide and alpha-tocopherol. 772 1

1. The influence of strain and sex on the effect of enflurane and isoflurane and administration on heme metabolism was investigated to identify the animal model which could best reproduce the biochemical signs of acute intermittent porphyria. 2. Enflurane produced 35% and 80% increases in ALA-S activity only in CF1 male and female mice, respectively, whereas isoflurane induced 40% enzyme activity in CF1 male. 3. CF1 males showed around 35% decrease in blood PBGase and PBG-deaminase after administration of enflurane, whereas isoflurane provoked a striking inhibition (70%) in males of the C57 strain. 4. Enflurane produced alterations in heme synthesis, which would fit a model of acute porphyria in CF1 male mice. On the other hand, isoflurane would mimic biochemical alterations of this porphyria in C57 males.
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PMID:Strain and sex differences in the effect of enflurane and isoflurane on heme metabolism in mice. 890 83

Hemodialysed patients with no history of porphyria may present neurological symptoms similar to those seen in acute porphyrias. Porphyria has been associated with an increase in plasma levels of 5-aminolevulinic acid and porphobilinogen. Our aim was to evaluate these parameters and the activities of the enzymes involved in the first steps of heme metabolism in non-porphyric hemodialysed patients. The activities of 5-aminolevulinate dehydratase and deaminase were determined in red blood cells (RBC) from 78 hemodialysed patients, before and after dialysis. Plasma levels of 5-aminolevulinic acid, porphobilinogen and zinc were also measured. These parameters were also measured in 40 volunteers to obtain controls levels. The levels of 5-aminolevulinic acid (0.98 +/- 0.09 microgram/ml) and porphobilinogen (1.32 +/- 0.13 micrograms/ml) were raised in non-porphyric patients prior to hemodialysis (P < 0.001) compared with controls (5-aminolevulinic acid 0.13 +/- 0.02 microgram/ml; porphobilinogen 0.90 +/- 0.09 microgram/ml). After dialysis there was a decrease in both 5-aminolevulinic acid (to 0.61 +/- 0.05 microgram/ml) and porphobilinogen (to 1.10 +/- 0.16 micrograms/ml) although both parameters remained higher than controls (P < 0.001). The activities of both 5-aminolevulinate dehydratase (0.550 +/- 0.095 U/ml RBC), and deaminase (54.13 +/- 9.13 U/ml RBC) were diminished in blood samples of patients before dialysis (P < 0.001) compared to controls (dehydratase 0.975 +/- 0.115 U/ml RBC; deaminase 77.32 +/- 10.00 U/ml RBC). After dialysis 5-aminolevulinate dehydratase activity was partially recovered (to 0.666 +/- 0.100 U/ml RBC) while deaminase returned to normal values (73.45 +/- 9.46 U/ml RBC). The plasma zinc concentration in hemodialysed patients (44 +/- 12 micrograms/100 ml) was significantly lower than controls (105 +/- 30 micrograms/100 ml, P < 0.001). Addition of 22.5 mM zinc to the dehydratase reaction mixture raised the activity of 5-aminolevulinate dehydratase in blood samples of hemodialysed patients taken before and after dialysis. The study reports a partial loss of activity of 5-aminolevulinate dehydratase and deaminase activities in red blood cells from non-porphyric patients undergoing hemodialysis. Since plasma zinc levels were below normal in hemodialysed patients, and the activity of 5-aminolevulinate dehydratase could be restored by the addition of zinc, it is suggested that these abnormalities in heme metabolism may be explained by altered zinc and associated antioxidant status following dialysis.
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PMID:Altered 5-aminolevulinic acid metabolism leading to pseudoporphyria in hemodialysed patients. 892 Jun 40

Four types of hepatic porphyria (acute intermittent porphyria; hereditary coprophorphyria; variegate porphyria; delta-aminolevulinate dehydratase deficiency porphyria) present clinically with an identical neurological syndrome. Symptoms include severe abdominal pain, vomiting, constipation, hypertension, tachycardia, and bladder dysfunction. These symptoms have been ascribed to autonomic neuropathy. Other symptoms are motor weakness and sensory involvement, which correlate with peripheral axonal neuropathy, and mental symptoms occurring without clear morphological findings in the cerebrum. The pathogenetic mechanisms which lead to the neurological dysfunction have remained poorly understood, partly due to the lack of a suitable animal model of these rare disorders. Two hypotheses, the possible neurotoxicity of delta-aminolevulinate (ALA) and heme deficiency in nervous tissue are discussed and corresponding data from porphobilinogen-deaminase deficient mice are presented. The present evidence suggests that multiple mechanisms interact in causing the varied symptoms, including ALA interaction with GABA receptors, altered tryptophan metabolism, and possibly heme depletion in nerve cells.
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PMID:Acute porphyrias: pathogenesis of neurological manifestations. 951 77

Acute intermittent porphyria (AIP) is the most frequent acute porphyria. Symptomatic patients and asymptomatic gene carriers are characterized by a reduction of their porphobilinogen-deaminase (PBG-D) activity to 50%, which is sufficient for porphyrin biosynthesis. PBG-D is encoded by two different mRNAs which are expressed in a tissue-specific manner. In classical AIP, the enzyme activity is reduced in erythroblasts and all other heme-forming body cells, whereas in the variant form of AIP, the PBG-D activity in erythroid tissues remains normal. Acute porphyria attacks can occur in gene carriers when the biosynthesis of heme is increased by drugs, low calorie intake, alcohol consumption or infections. Under these conditions, PBG-D cannot convert the precursors adequately so that PBG and delta-aminolevulinate accumulate. This may lead to neurovisceral symptoms and other neurological complications which are potentially life threatening. In patients with AIP, mutation analysis by PCR-DGGE (denaturing gradient gel electrophoresis) is becoming increasingly important since it also permits rapid identification of their presymptomatic relatives. Using this technique, more than 120 mutations have been identified in the PBG-D gene. When identified, the family members are informed about their genetic predisposition and are taught how to prevent porphyric attacks. Here, I illustrate this preventive strategy by describing a German kindred of an affected patient with the variant form of AIP with 17 family members.
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PMID:Acute intermittent porphyria: mutation analysis and identification of gene carriers in a German kindred by PCR-DGGE analysis. 1034 7

Drugs and toxins precipitate life-threatening acute attacks in patients with intermittent acute porphyria. These materials may act by directly inhibiting enzyme activity, thus further reducing porphobilinogen (PBG) deaminase activity below the ca. 50% level that results from the gene defect. To test this, we studied the effects of drugs that precipitate acute attacks (lead, phenobarbital, griseofulvin, phenytoin, sulfanilamide, sulfisoxazole, 17alpha-ethinyl estradiol, 5beta-pregnan-3alpha-ol-20-one), drugs that are safe (lithium, magnesium, chlorpromazine, promethazine), and those with uncertain effects (ethyl alcohol, imipramine, diazepam, haloperidol) on activity of PBG deaminase in vitro and in vivo. In the in vitro studies, of PBG deaminase from human erythrocytes from normals and individuals with IAP, only lead (> or = .01 mM) inhibited enzyme activity. Chlorpromazine (> or = .01 mM), promethazine (> or = .01 mM) and imipramine (1 mM) seemed to increase enzyme activity. In most in vivo experiments, male rats were injected intraperitoneally with test material twice daily for 3 days and once on day four; and erythrocyte and hepatic PBG deaminase activity was assayed thereafter. Effects on enzyme activity were observed only with 17alpha-ethinyl estradiol (0.05 microg/kg/day; reduction of 11% in erythrocyte enzyme [NS], and of 20% in liver enzyme [P=.02]), and imipramine (12.5 mg/kg/day; reduction in erythrocyte enzyme activity of 13% [P<.001]). Rats given lead acetate in their drinking water (10 mg/ml) for the first 60 days of life, resulting in high blood and liver lead levels, had increased erythrocyte PBG deaminase (167% of control; P=.004). Thus, enzyme inhibition by lead in vitro was not reflected in a similar in vivo inhibition. The only inhibitory effects in vivo, with ethinyl estradiol and imipramine, appear to be mild and biologically inconsequential. We conclude that inhibition of PBG deaminase activity by materials that precipitate acute attacks is an unlikely mechanism by which these materials exert their harmful effects in patients with IAP.
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PMID:The effect of therapeutic drugs and other pharmacologic agents on activity of porphobilinogen deaminase, the enzyme that is deficient in intermittent acute porphyria. 1041 26

The aims of the present study were to explore the expression pattern of haem biosynthesis enzymes in circulating cells of patients affected by two types of porphyria (acute intermittent, AIP, and variegate porphyria, VP), together with the antioxidant enzyme pattern in AIP in order to identify a possible situation of oxidative stress. Sixteen and twelve patients affected by AIP and VP, respectively, were analysed with the same numbers of healthy matched controls. Erythrocytes, neutrophils and peripheral blood mononuclear cells (PBMCs) were purified from blood, and RNA and proteins were extracted for quantitative real time PCR (qRT-PCR) and Western-blot analysis, respectively. Porhobilinogen deaminase (PBGD) and protoporphyrinogen oxidase (PPOX) gene and protein expression was analysed. Antioxidant enzyme activity and gene expression were additionally determined in blood cells, together with protein carbonyl content in plasma. PBMCs isolated from AIP patients presented low mRNA levels of PBGD when compared to controls, while PBMCs isolated from VP patients presented a decrease in PPOX mRNA. PPOX protein content was higher in AIP patients and lower in VP patients, compared to healthy controls. Regarding antioxidant enzymes, PBMCs and erythrocyte superoxide dismutase (SOD) presented statistically significant higher activity in AIP patients compared to controls, while catalase activity tended to be lower in these patients. No differences were observed regarding antioxidant gene expression in white blood cells. Circulating cells in AIP and VP patients present altered expression of haem biosynthetic enzymes, which could be useful for the differential diagnosis of these two types of porphyria in certain difficult cases. AIP patients present a condition of potential oxidative stress similar to VP patients, evidenced by the post-transcriptional activation of SOD and possible catalase impairment.
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PMID:Haem Biosynthesis and Antioxidant Enzymes in Circulating Cells of Acute Intermittent Porphyria Patients. 2778 71

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