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)

Porphorbilinogen oxygenase (EC 4.2.1.24) was associated with the microsomal fraction of bone marrow in normal rats and in rats submitted to erythropoietic stress, while porphobilinogen deaminase (EC 4.3.1.8) of the same origin was present in the cytosol. An NADPH-dependent electron-donor system for the oxygenase was also present in the microsomes of the bone marrow. Under conditions of erythropoietic stress caused by hypoxia, the activities of both enzymes were found to be inversely correlated. While the oxygenase showed minimum activity between the 4th and 8th day of hypoxia, porphobilinogen deaminase reached its maximum activity during this period. After the 8th day of hypoxia, oxygenase activity increased while deaminase activity decreased. The NADPH-dependent electron-transport system necessary for the microsomal oxygenase activity was largely inactivated after the 10th day of hypoxia, while oxygenase activity was not affected. The particulate porphobilinogen oxygenase could be solubilized from the bone marrow microsomes with 1% deoxycholate or 0.5 M KCl. In addition, the oxygenase was also released by freezing and thawing the microsomes isolated from bone marrow of rats which had been submitted to an erythropoietic stress (hypoxia or phenylhydrazine). The enzyme solubilized with deoxycholate or KCl showed a high molecular weight form and a low molecular weight form (Mr 25 000). The former could be transformed into the latter either by treatment with 2 M KCl or by succinylation. When the oxygenase was solubilized by freezing and thawing a third molecular weight form (Mr 50 000) also appeared. The solubilized enzyme could be succinylated without loss of its catalytic activity, while the membrane-bound enzyme could not be succinylated.
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PMID:The regulation of porphobilinogen oxygenase and porphobilinogen deaminase activities in rat bone marrow under conditions of erythropoietic stress. 369 63

Porphyria was induced in C57BL/10 mice with iron overload by a single oral dose (100 mg/kg) of hexachlorobenzene (HCB). Within 2 weeks hepatic uroporphyrinogen decarboxylase (EC 4.1.1.37) was inhibited, reaching a maximum (greater than 95%) at 6-8 weeks. There was no recovery by 14 weeks, despite a fall in liver HCB concentrations to only 6% of the day-3 value. The major rise in hepatic porphyrin levels occurred after 4 weeks and secondary inhibition of uroporphyrinogen synthase (EC 4.2.1.75) was inferred from the progressively greater proportion of uroporphyrin I present relative to the III isomer. Plasma alanine aminotransferase (EC 2.6.1.2) activity was also elevated. Although, in further studies, total microsomal cytochrome P-450 content and ethoxyphenoxazone de-ethylase activity reached a peak a few days after dosing and had declined significantly at the time of maximum inhibition of the decarboxylase, additional treatment of HCB-dosed mice with a cytochrome P1-450 inducer, beta-naphthoflavone, enhanced the inhibition, whereas piperonyl butoxide, an inhibitor of cytochrome P-450, partially protected. Uroporphyrinogen decarboxylase was not radiolabelled in vivo by [14C]HCB. There was no major difference in the ability to hydroxylate HCB between hepatic microsomes from induced C57BL/10 mice and those from the insensitive DBA/2 strain. By contrast, lipid peroxidation, in the presence of NADPH, was 8-fold greater in control C57BL/10 microsomes than in DBA/2 microsomes and was stimulated by iron treatment (although not by HCB). The results suggest that the inhibition of hepatic uroporphyrinogen decarboxylase is unlikely to be due to a direct effect of a metabolite of HCB but to another process requiring a specific cytochrome P-450 isoenzyme and an unknown iron species.
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PMID:Mechanistic studies of the inhibition of hepatic uroporphyrinogen decarboxylase in C57BL/10 mice by iron-hexachlorobenzene synergism. 380 Sep 66

The effects of thallium chloride (TlCl3.4H2O) on hepatocyte structure and function were studied in male rats at 16 hr following treatment by ip injection with doses of 0, 50, 100, and 200 mg/kg. Ultrastructural examination of hepatocytes from thallium-treated rats showed a dose-related loss of ribosomes from the endoplasmic reticulum and proliferation of the rough endoplasmic reticulum segment. Generalized mitochondrial swelling and increased numbers of electron-dense autophagic lysosomes were also observed. Morphometric analysis of hepatocytes from thallium-treated rats disclosed a 3-fold increase in the volume density of the lysosomal compartment and a 1.3-fold increase in the volume density of mitochondrial. Surface density measurements of mitochondrial and endoplasmic reticulum membranes showed dose-related increases in the surface density of both inner and outer mitochondrial membranes as well as of the rough endoplasmic reticulum. These structural changes were associated with pronounced increases in the specific activities of the mitochondrial membrane-associated enzymes monoamine oxidase and ferrochelatase to 145 and 144% of control values, respectively, and a 42% decrease in the activity of aminolevulinic acid (ALA) synthetase. Similarly, structural alteration of the endoplasmic reticulum in thallium-treated rats was associated with concomitant impairment of the microsomal enzymes NADPH cytochrome c (P-450) reductase, aniline hydroxylase, and aminopyrene demethylase to a maximum of 49, 43, and 77% of activities seen in untreated controls, respectively. In contrast, the non-membrane-bound enzymes malate dehydrogenase, ALA dehydratase, and uroporphyrinogen I synthetase were unaltered in vivo following thallium treatment at any doses. These results indicate that thallium-induced alteration of hepatic biochemical processes may arise from physical disruption of the membranal integrity of subcellular organelles with which those processes are functionally associated. These findings are consistent with those from previous studies in demonstrating a positive quantitative correlation between metal-induced subcellular organelle membrane structural injury and impairment of associated biological functions in vivo.
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PMID:Alteration of hepatocellular structure and function by thallium chloride: ultrastructural, morphometric, and biochemical studies. 396 12