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:2.5.1.61 (porphobilinogen deaminase)
637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary enzyme deficiency in porphyrias can be recognized in blood cells. In the red cell four enzymes of heme biosynthesis can be detected: porphobilinogen synthase (delta-aminolevulinic acid dehydrase), uroporphyrinogen synthase, cosynthase, and decarboxylase. A decrease of porphobilinogen synthase is observed in lead intoxication and in a new type of hereditary acute porphyria with nearly total enzyme deficiency in the homozygous state with a residual activity of 1-2% of controls. In another recessive condition, congenital erythropoietic porphyria, the deficient uroporphyrinogen cosynthase shows an activity between 1 and 20%. Acute intermittent porphyria is characterized by diminished uroporphyrinogen synthase which allows the recognition of gene carriers in red cells. In the genetic type of porphyria cutanea tarda triggered by alcohol, oral contraceptives, and liver damage the uroporphyrinogen decarboxylase is decreased to about 50%. In hepatoerythropoietic porphyria, a homozygous variant of porphyria cutanea tarda, decarboxylase activity was found below 10% of controls. With exception of congenital erythropoietic, hepatoerythropoietic porphyria, and lead poisoning enzyme deficiencies of porphyrin metabolism in red cells do not lead to anemia.
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PMID:[Enzyme deficiency of erythrocytes in human porphyria]. 129 74

The frequency of low erythrocyte porphobilinogen deaminase (PBGD) activity was investigated in 2234 blood donors and in 30 patients with acute intermittent porphyria. The mean enzyme activities (+/- SD) were 3.38 +/- 0.58 U and 1.82 +/- 0.41 U, respectively. Eighteen blood donors without any history of symptoms of porphyria or haematological disease had low PBGD activity (less than 2.20 U), and they were studied further. All of them also had subnormal concentrations of the erythrocyte enzyme protein, as determined by an immunological method. Lymphocyte PBGD activity was within the normal range, but this parameter does exhibit a wide overlap between normal and porphyric values. Urinary excretion of porphobilinogen was moderately increased in two of the blood donors. In four of the 18 families of the blood donors with low PBGD activity several first-degree relatives had low erythrocyte enzyme activity, consistent with a dominant mode of inheritance. The 5-aminolaevulinic acid loading-test was normal in the blood donors with familial occurrence of low erythrocyte PBGD. It is concluded that inherited defects in erythrocyte PBGD occurred among Finnish blood donors with a frequency of about 1 in 500. The defects may be identical with those in acute intermittent porphyria (AIP), but other mechanisms are also possible, e.g. a mutation in the erythroid-specific part of the PBGD gene.
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PMID:Frequency of low erythrocyte porphobilinogen deaminase activity in Finland. 158 64

Liver uroporphyrinogen synthetase activity was measured in 45 mice, divided in three groups. The mice of the 1st group served as controls, those of the 2nd starved for 24 hours, while those of the 3rd were injected intraperitoneally with phenobarbital. The enzymic activity was found significantly (p less than 0.001) lower in the animals of the 2nd group (17.49 +/- 2.25 nmol/g/h) and higher in those of the 3rd (25.82 +/- 3.73 nmol/g/h) as compared to the controls (20.89 +/- 2.11 nmol/g/h). If these effects also exist in the human it could be suggested that starvation may be doubly harmful for the patients with acute intermittent porphyria by aggravating both their enzymic disorders. On the contrary, in the case of phenobarbital its undesired effect on porphyria may be moderated by a simultaneous induction of the uroporphyrinogen synthetase.
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PMID:[Effect of starvation and phenobarbital on the activity of liver uroporphyrinogen synthetase]. 176 43

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

All nucleated animal cells synthesize heme to provide the prosthetic group of respiratory cytochromes. Large amounts of heme are synthesized by erythroid cells for hemoglobin production and by liver cells for drug-induced cytochromes P450. This review focuses on the first enzyme of the heme biosynthetic pathway, 5-aminolevulinate synthase (ALAS), which catalyzes the rate-controlling step in liver and possibly other tissues. We report that there are two distinct human genes for ALAS: one, a housekeeping gene, is probably ubiquitously expressed while the other is active only in erythroid tissue. By contrast it has been reported that, for porphobilinogen deaminase, the third enzyme of the heme pathway, there is a single human gene with two promoters; one functional in all tissues, the other erythroid specific. In liver, transcription of the housekeeping ALAS gene is induced by drugs and repressed by heme. Heme also acts in a novel way to prevent transport of ALAS into mitochondria, its site of function. Porphyrias result from inherited defects in enzymes of the heme pathway subsequent to ALAS and the molecular abnormality is now known for the most common subtype of acute intermittent porphyria. In developing red cells, levels of ALAS are regulated by increased gene transcription and by a post-transcriptional mechanism, in which iron most probably controls translation of erythroid ALAS mRNA through an iron-responsive element identified in the 5' untranslated region of the mRNA. The human erythroid ALAS gene is located on the X-chromosome, suggesting that a defect in this gene may be responsible for X-linked sideroblastic anemias.
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PMID:Molecular regulation of 5-aminolevulinate synthase. Diseases related to heme biosynthesis. 209 58

A child who was grossly malnourished and who showed increased excretion of porphyrin and porphyrin precursor had normal activity of erythrocyte porphobilinogen deaminase (EC 4.3.1.8) and leukocyte protoporphyrinogen oxidase (EC 1.3.3.4). Clinical symptoms, coincident with the excretion of rose-colored urine, were consistent with the diagnosis of an acute porphyria. The disease resolved spontaneously after the withdrawal of carbamazepine and sodium valproate and the commencement of parenteral nutrition with subsequent carbohydrate loading. In addition to normal concentrations of enzyme activities, the patient is unusual in presenting before puberty and in having no family history of porphyria.
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PMID:Variant acute intermittent porphyria in a child. 233 98

1. Acute intermittent porphyria (AIP) is sometimes termed a 'pharmacogenetic' disease. patients with genetic deficiency of the enzyme porphobilinogen deaminase are liable to develop acute attacks of porphyria if exposed to a variety of drugs. 2. Two patients are reported who had no evidence of deficiency of erythrocyte porphobilinogen deaminase yet developed typical attacks of AIP while on anticonvulsant therapy. 3. Normal activity of erythrocyte porphobilinogen deaminase does not completely exclude porphyria. 4. Acute porphyria should be suspected if clinical deterioration occurs during therapy with anticonvulsants, or other porphyrinogenic drugs, even in the absence of an underlying genetic defect in haem synthesis in peripheral blood cells.
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PMID:Acute intermittent porphyria in two patients on anticonvulsant therapy and with normal erythrocyte porphobilinogen deaminase activity. 249 68

A previously unrecognized form of dual porphyria has been identified in four patients. One male and one female with acute symptoms were diagnosed as having acute intermittent porphyria (AIP), and two males with cutaneous and acute symptoms were diagnosed as having porphyria cutanea tarda (PCT). Biochemically, the excretion of haem precursors showed a complex constellation, with signs characteristic of both AIP and PCT. In one male, a clinical course with both overt PCT and acute manifestations of AIP was observed. Enzyme studies of haem biosynthesis in erythrocytes revealed a dual deficiency, with decreased activity of both porphobilinogen deaminase, as seen in AIP, and uroporphyrinogen decarboxylase, as seen in PCT. A family study showed that the two disorders do not consistently segregate together. These findings suggest that the dual porphyria reflects a double heterozygous condition of coexistent AIP and PCT genes in the same subject.
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PMID:New form of dual porphyria: coexistent acute intermittent porphyria and porphyria cutanea tarda. 249 57

To study the existence of different mutations in acute intermittent porphyria, erythrocyte porphobilinogen deaminase activity and enzyme protein concentration were investigated in 125 porphyria gene carriers from 31 families, and in 121 apparently healthy controls. Porphobilinogen deaminase concentration (micrograms/gHb) was quantified using a recently developed double-sandwich ELISA. The ratio of enzyme catalytic activity to the concentration of enzyme protein was expressed as the porphobilinogen specific activity (nkat/g). The controls had a mean porphobilinogen deaminase concentration of 160 +/- 35 micrograms/gHb and a specific activity of 762 +/- 127 nkat/g. Two different types of mutation causing acute intermittent porphyria were detected. The majority (91%) of gene carriers, from 25 families, had a diminished porphobilinogen deaminase concentration of 102 +/- 18 micrograms/gHb, with a slightly lowered specific activity of 634 +/- 105 nkat/g. In 9% of the gene carriers, representing six different families, an increase in porphobilinogen deaminase concentration to 269 +/- 46 micrograms/gHb, and a highly significant reduction in specific activity to 234 +/- 48 nkat/g, were found, which indicates the presence of a different mutation.
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PMID:Mutations in acute intermittent porphyria detected by ELISA measurement of porphobilinogen deaminase. 260 15

A coexistent dual deficiency of porphobilinogen deaminase (PBG-D; EC 4.3.1.8) and uroporphyrinogen decarboxylase (EC 4.1.1.37) in erythrocytes was recognized in five individuals, four males and one female. Clinically, the female and one male were diagnosed as suffering from acute intermittent porphyria (AIP), and the other two males were diagnosed as having porphyria cutanea tarda (PCT). Biochemically, the excretion pattern of urinary and fecal heme precursors exhibited a complex constellation with signs characteristic for both AIP and PCT. A coexistent dual enzyme deficiency of PBG-D and URO-D could be confirmed by repeated studies over 10 years. Clinical courses of both disease manifestations were observed. Family investigations have shown that the two disorders do not consistently segregate together. The findings suggest that the dual porphyria reflects a double heterozygous condition of coexistent AIP and PCT genes in the same individual.
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PMID:Dual porphyria in double heterozygotes with porphobilinogen deaminase and uroporphyrinogen decarboxylase deficiencies. 272 Oct 23


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