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)

In two young patients with acute hepatic porphyria syndrome and persisting paralyses, which increased in intensity during intermittent occurring crisis, the activity of erythrocyte porphobilinogen synthase (delta-aminolevulinic acid dehydratase) was found to be considerably diminished, below 1% of the value of normal control persons. In contrast, the activity of uroporphyrinogen synthase was normal. Both patients have been excreting high quantities of delta-aminolevulinic acid and porphyrins in urine for years. Lead intoxication has definitively been excluded. Since the relatives also show lower activities in porphobilinogen synthase, the disease of these two patients is probably a new enzymatic type of inherited acute hepatic porphyria, the excretion profile of which is qualitatively completely different from those of the known acute porphyrias. The discovery of this porphyria confirms the theory of overlapping transition in the biochemical and clinical symptoms and analogies among acute hepatic porphyrias.
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PMID:New type of hepatic porphyria with porphobilinogen synthase defect and intermittent acute clinical manifestation. 51 4

In two male patients with acute hepatic porphyria and persisting paralysis which increased in intensity intermittently, the activity of porphobilinogen synthase (PBG-S; delta-aminolevulinic acid dehydr(at)ase) was diminished in peripheral erythrocytes and bone marrow cells below 3% of normal controls. In contrast, the activities of uroporphyrinogen synthase and decarboxylase were normal. Both patients have been excreting high quantities of delta-aminolevulinic acid and porphyrins in urine for years. Lead intoxication and tyrosinemia could definitely be excluded. There was no experimental evidence for the existence of an inhibitor to PBG-S in urine, serum and erythrocytes from these two patients. The PBG-S deficiency was confirmed after DEAE cellulose chromatography: the concordance of relative and specific activity before and after chromatography of PBG-S from patients and controls differs from the findings in lead poisoning. A mutation of PBG-S probably at the level of the structural gene is concluded as the molecular basis of the inherited PBG-S defect porphyria. Since the relatives also show lower activities of PBG-S (approximately 50% of controls), the disease of these two patients represents a new enzymatic type of inherited acute hepatic porphyria, the excretion profile of which is qualitatively completely different from those of the known acute porphyrias. The discovery of this porphyria confirms the theory of overlapping transition in the biochemical signs and clinical symptoms as well as analogies among the acute hepatic porphyrias and lead poisoning.
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PMID:New type of acute porphyria with porphobilinogen synthase (delta-aminolevulinic acid dehydratase) defect in the homozygous state. 706 77

The study was aimed to assess the protective efficacy of zinc against hemo and hematotoxicity induced by lead. Two groups of 8 rats each, were administered lead acetate 20 mg/kg bw (ip) for 3 days. One group in addition was injected 5 mg/kg bw (ip) zinc acetate for next three days. A third group of 8 rats was given three injections of normal saline and served as control. All the animals were sacrificed on eighth day and assessed for hematological changes, heme synthesizing pathway enzymes, hepatic drug metabolizing status and sulfhydryl levels in blood and liver. Lead administration resulted in decreased hemoglobin, increased reticulocytosis, depression of delta aminolevulinic acid dehydratase (ALAD) and uroporphyrinogen I synthetase (UPS) activity in blood and liver. In vitro metabolism of drugs aminopyrine, aniline and p-nitroanisole by liver homogenate and in vivo metabolism of pentabarbitone was also reduced in lead exposed rate. Zinc treated rats showed improved hematological profile and activated ALAD and UPS activity, recovery of N-demethylation of aminopyrine and O-demethylation of p-nitroanisole and partial restoration of free thiol levels in blood and liver thereby indicating that zinc could confer protection against lead toxicity.
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PMID:Preventive action of zinc against lead toxicity. 858 50

The porphyrias are inherited or acquired metabolic disorders caused by a partial deficiency in one of the enzymes of the heme biosynthetic pathway. Eight enzymes are utilized in the synthesis of heme. An enzyme defect in one of the last seven enzymes will result in one of the seven different forms of porphyria, some of which have similar signs and symptoms. This article describes six diabetic, azotemic patients with no prior history of porphyria, who developed a syndrome similar to acute intermittent porphyria after initiation of treatment with erythropoietin. One of the patients developed the syndrome predialysis, whereas the remaining patients were on maintenance hemodialysis. The symptoms varied but all resolved when erythropoietin was discontinued and reappeared in four cases when erythropoietin was restarted. In all of the patients, the enzyme aminolevulinic acid-dehydratase (ALA-D) was low and the uroporphyrinogen synthase was normal. This enzyme abnormality suggests an acquired form of delta-aminolevulinic acid dehydratase porphyria (ADP). Lead toxicity, succinylacetone, and zinc deficiency are known to depress ALA-D, but these conditions were not present. The development of the acute porphyria syndrome while the patients were receiving pharmacological doses of erythropoietin, which resolved when the drug was stopped, suggests that by stimulating heme synthesis, erythropoietin may unmask an enzyme deficiency resulting in the clinical expression of ADP. The patients responded favorably to a regimen that included discontinuation of erythropoietin, tight blood sugar control, maintaining the hematocrit above 30%, and a KT/V, a measure of dialysis adequacy, of 1.5 in the hemodialysis group. Plasmapheresis accelerated the recovery when used in two patients.
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PMID:Porphyria syndrome associated with diabetic nephrosclerosis and erythropoietin. 1743 69