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

Experiments were carried out to investigate the possibility of inducing porphyria in human hepatocytes and HepG2 cells in culture. After treatment with hexachlorobenzene, 3-methylcholanthrene, phenobarbital or dimethyl sulfoxide, protoporphyrin was the predominating porphyrin accumulating in presence of delta-aminolevulinic acid. The typical uroporphyrin accumulation, as is seen in hexachlorobenzene-induced porphyria in vivo, was absent. In HepG2 cells, the activities of uroporphyrinogen decarboxylase and porphobilinogen deaminase were not influenced by cytochrome P-450 inducers, hexachlorobenzene or dimethyl sulfoxide during 48 h of culture. Therefore, the use of these cells in the study of porphyria cutanea tarda does not seem promising.
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PMID:Porphyrin synthesis by human hepatocytes and HepG2 cells--effects of enzyme inducers and delta-aminolevulinic acid. 185 Jan 74

5-Aminolevulinic acid, porphyrin and chlorophyll contents as well the activities of 5-aminolevulinic acid dehydratase and PBG deaminase were studied in selenium treated mung bean seedlings. Selenium had no effect on 5-aminolevulinic acid synthetic ability but inhibited 5-aminolevulinic acid dehydratase and PBG deaminase activities. Further, it was observed that selenium induced accumulation of protoporphyrin-IX and Mg-protoporphyrin ester and decreased chlorophyll levels in both light and dark-grown seedlings. The results suggest the possible regulatory role of selenium on chlorophyll synthesis by interacting with sulfhydryl containing enzymes 5-aminolevulinic acid dehydratase and porphobilinogen deaminase.
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PMID:Selenium as a novel regulator of porphyrin biosynthesis in germinating seedlings of mung bean (Phaseolus vulgaris). 207 2

The activities of 5-aminolaevulinate dehydrase (ALA-D), hydroxymethylbilane synthase (HMB-S), uroporphyrinogen III synthase (URO-S) and uroporphyrinogen decarboxylase (URO-D) in the erythrocytes of alcoholics were assayed and compared with those in controls and abstaining alcoholics. The HMB-S and URO-S activities in alcoholics were significantly higher than the controls and there were significant correlations between enzyme activities and mean corpuscular volume (MCV). Alcoholics abstaining from alcohol over a nine-month period showed a return to normal enzyme activities in parallel with the normalization of their MCV. Abstaining alcoholics thus all had normal HMB-S and URO-S activities. The ALA-D and URO-D activities of alcoholics were not significantly different from controls or from abstaining alcoholics. Alcohol appears to have a selective effect on the haem biosynthetic enzymes in the erythron.
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PMID:High performance liquid chromatographic studies of erythrocytes haem biosynthetic enzyme activities in alcoholic macrocytosis. 228 50

3 patients with lead intoxication are demonstrated. The analysis of porphyrins and porphyrin precursors led to the tentative diagnosis which was confirmed by the increased lead levels. The increased urinary excretion of porphyrins and of delta-aminolevulinic acid, the decreased activity of uroporphyrinogen synthase and the increased protoporphyrin content (absorption maximum 595 nm) in the red cells suggested the diagnosis before the lead values of the patients were known. Clinical signs of the patients included gastrointestinal and neurological symptoms. It is assumed that the lead intoxication in these patients was caused by occupational exposition.
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PMID:[Do not forget: lead poisoning]. 260 5

The pre-clinical diagnosis of acute intermittent porphyria (AIP) is important because acute attacks can be brought about by drugs, liver toxins, hormonal changes and diet. There also may be no obvious precipitating agent. The discovery that the activity of uroporphyrinogen I synthase (URO-S) activity in the red blood cells of patients with AIP is half that found in normal persons is of great value in diagnosing this disorder and also appears useful in detecting patients with the latent disease who have normal urinary delta-aminolevulinic acid and porphobilinogen excretion. It also appears to distinguish other types of porphyria from acute intermittent porphyria. It must also be recognized that some red blood cells URO-S determinations will yield indeterminate results; therefore, repeat assays, including examination of kinship, will improve discrimination and confidence in the final diagnosis.
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PMID:Erythrocyte uroporphyrinogen I synthase activity as an indicator of acute porphyria. 275 Dec 41

Acute intermittent porphyria is a genetic hepatic porphyria characterized by acute gastrointestinal and neurological symptoms, and accompanied by excess excretion of delta-aminolevulinic acid and porphobilinogen. Here, we report a case of acute intermittent porphyria with attacks of abdominal pain, an elevated serum thyroxine level, and hypercholesterolemia with an increased level of high-density lipoprotein-cholesterol concentration. The diagnosis of acute intermittent porphyria was confirmed by a high urinary excretion of porphobilinogen and a low level of erythrocyte hydroxymethylbilane synthase activity. After being treated with a high carbohydrate intake and propranolol, the patient improved gradually during the following 3 weeks. The patient remained asymptomatic during the 6-month follow-up period. The serum thyroxin and cholesterol levels returned to normal 6 months later. In conclusion, we suggest that for any patient who presents with unexplained abdominal pain, abnormal thyroid function and hypercholesterolemia, a simple Watson-Schwartz urine test should be performed for the screening of acute intermittent porphyria. If the Watson-Schwartz test is positive, the erythrocyte hydroxymethylbilane synthase activity should be determined to confirm the diagnosis of acute intermittent porphyria.
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PMID:Abnormal thyroid function and hypercholesterolemia in a case of acute intermittent porphyria. 280 66

The short-term effects of sodium valproate (VPA) on haem biosynthesis were assessed in a placebo-controlled crossover trial in eight healthy male subjects who ingested VPA 500 mg t.i.d. and matched placebo for 5 days. All showed augmented activity of leucocyte 5-aminolaevulinate synthase (ALA-S) activity, the rate-limiting enzyme of the haem biosynthetic pathway, following 3 and 5 days of VPA treatment (P less than 0.001). This was accompanied by increased urinary excretion of 5-aminolaevulinic acid (ALA; P less than 0.02) and total porphyrins (P less than 0.01). Mean (+/- SD) total VPA concentrations on day 3 (89 +/- 16 mg 1-1) and day 5 (91 +/- 22 mg 1-1) were within the target range for the drug. The long-term effects of VPA administration were examined in epileptic patients on established monotherapy. Leucocyte ALA-S activity (P less than 0.001), and daily urinary excretion of porphobilinogen (P less than 0.01) and total porphyrins (P less than 0.01) were all higher than in age-matched controls. No significant differences in erythrocyte ALA-dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase activities were found between the groups. These data suggest that VPA is porphyrinogenic in man and cannot be recommended as safe for seizure management in the porphyric patient.
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PMID:Effects of sodium valproate on haem biosynthesis in man: implications for seizure management in the porphyric patient. 313 Feb 56

The subcellular location of the two porphyrin-synthesis enzymes 5-aminolaevulinate dehydratase (ALAD) and porphobilinogen deaminase (PBGD) was investigated in Pisum sativum (pea) leaves and spadices of Arum (cuckoo-pint). Throughout the tissue-fractionation procedures the distribution of the two enzymes paralleled that of the plastid marker enzyme (ADP-glucose pyrophosphorylase), even in Arum, a tissue where the synthesis of non-plastid haem is predominant. The distribution of cytosolic marker enzyme (lactate dehydrogenase) was significantly different from that of ALAD and PBGD and, although purified mitochondria from both species had some residual activity, this was always less than contaminating plastid marker enzyme. The results suggest that ALAD and PBGD are exclusively plastid enzymes. The significance of this for the role of plastids in cellular porphyrin synthesis is discussed.
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PMID:Subcellular localization of two porphyrin-synthesis enzymes in Pisum sativum (pea) and Arum (cuckoo-pint) species. 327 25

Altered hepatic microsomal drug metabolism has been reported to occur in afflicted with hyperbilirubinemia. Similarities of the chemical structures of hydroxymethylbilane, an intermediate in the biosynthesis of uroporphyrinogen, to bilirubin prompted investigations of the effect of bilirubin on the activity of uroporphyrinogen I synthase (porphobilinogen deaminase, EC 4.3.1.8) and the biosynthesis of heme. Bilirubin was found to be a reversible, noncompetitive inhibitor of uroporphyrinogen I synthase. The inhibition constant (Ki) for bilirubin was 1.5 microM. Bile acids had no effect on rat hepatic uroporphyrinogen I synthase activity. Hyperbilirubinemia was achieved in rats by biliary ligation in order to investigate whether elevated levels of bilirubin impair the biosynthesis of hepatic heme in vivo. The relative rate of heme biosynthesis, as measured by the rate of incorporation of delta-[4-14C]aminolevulinic acid into heme, was decreased 59% 24 h after biliary obstruction. The levels of hepatic microsomal heme and cytochrome P-450 were decreased by 43 and 40%, respectively, 72 h after biliary obstruction. The activities of hepatic delta-aminolevulinic acid synthase and uroporphyrinogen I synthase were increased by 39 and 46%, respectively, 72 h after biliary obstruction. During the 48- to 72-h period following biliary obstruction, the urinary excretion of porphobilinogen and uroporphyrin was increased 3.0- and 3.5-fold, respectively, whereas, the urinary excretion of delta-aminolevulinic acid was not altered. During this 48-to 72-h time interval following biliary obstruction, 100% of the uroporphyrin was excreted as isomer I. These results indicate that bilirubin is capable of depressing the biosynthesis of rat hepatic heme and thus cytochrome P-450-mediated drug metabolism by inhibition of the formation of uroporphyrinogen. These findings are a plausible mechanism for reports of impaired clearance of various drugs in patients afflicted with hyperbilirubinemic disease states.
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PMID:Inhibition of the biosynthesis of uroporphyrinogen and heme in rat liver during obstructive jaundice produced by bile duct ligation. 396 18

Uroporphyrin I is found in high concentration in the bones, teeth, blood, soft tissues, and urine of the fox squirrel, Sciurus niger. The concentration of uroporphyrin in fox squirrel spleen is much higher than in liver, kidney or bone marrow, probably because of accumulation from phagocytosed red cells. Bleeding causes a marked increase in the uroporphyrin concentration of red cells and spleen, and a 3-8-fold increase in uroporphyrin excretion. Urinary excretion of delta-aminolevulinic acid and porphobilinogen is not greater in fox squirrels than in nonporphyric gray squirrels. Sciurus carolinensis, used as controls. In all these characteristics, as well as in the previously demonstrated deficiency of the enzyme uroporphyrinogen III cosynthetase in red cells, the physiological porphyria of fox squirrels resembles congenital erythropoietic porphyria, a hereditary disease of man and cattle. For squirrels differ in showing no evidence of cutaneous photosensitivity or hemolytic anemia. Uroporphyrinogen III cosynthetase activity is present in fox squirrel bone marrow at 1/10 its concentration in gray squirrel marrow. The fox squirrel enzyme is much more unstable than the gray squirrel enzyme, which provides a possible explanation for its low activity and for the overproduction of uroporphyrin I. It is unlikely that the deficiency of cosynthetase is due to its inactivation by excessive amounts of uroporphyrinogen I synthetase, because activity of the latter enzyme is the same in blood from fox and gray squirrels.Fox squirrel porphyria provides a convenient model for studies of pathogenesis of human congenital erythropoietic porphyria.
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PMID:Erythropoietic porphyria of the fox squirrel Sciurus niger. 468 90


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