Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vivo regulation by metal ions of the enzymes of heme metabolism in kidney-particularly of ALAS, the rate-limiting enzyme in heine formation- was investigated. Ni(2+) and Pt(4+), metals which do not enzymatically form metalloporphyrins, were found to regulate ALAS in kidney as they do in liver. The pattern of this regulation was generally similar to that observed with heme and metal ions in liver, i.e., a late increase in enzyme activity after an early period in which ALAS activity was unaltered or inhibited. The metals did not interact with the enzyme in vitro to alter its activity. In this study no direct reciprocal relationship between ALAS activity and total cellular heine content was demonstrated. The metal ions, particularly Pt(4+), also altered the activity of other enzymes of heme biosynthesis in kidney. Pt(4+) severely inhibited the activity of ALAD and UROS. Ni(2+) and Pt(4+) were potent inducers of heme oxygenase, the initial and rate-limiting enzyme in heine degradation. It is proposed that the physiological regulation of ALAS is mediated through the action of metal ions, rather than by the cellular content of heine, and that the regulation of ALAS by heine reflects the action of the central metal ion of heme rather than that of the entire metalloporphyrin complex. In this proposed mechanism for metal ion regulation of ALAS, the tetrapyrrole moiety of heine is considered to function principally as an efficient carrier of metal to the regulatory site for ALAS production, inasmuch as the tetrapyrrole ring itself has been shown in earlier studies not to have any effect on ALAS activity. The production of heine oxygenase is believed to be similarly regulated.
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PMID:Enzymes of heme metabolism in the kidney: regulation by trace metals which do not form heme complexes. 92 3

The regulation of the heme biosynthetic pathway in the kidney by various metals has been reviewed. In addition, a study on the effects of lead on renal heme biosynthesis after acute treatment of rats has been reported. Chronic low-level lead exposure in rats results in relatively small effects on renal heme biosynthetic pathway enzymes. After acute treatment of rats with lead, no effects on ALAD or UROS and mild, transitory effects on ALAS and ferrochelatase are observed. The intracellular binding of lead within intranuclear inclusion bodies in the proximal tubule cells and to high-affinity cytosolic lead-binding proteins probably protects sensitive subcellular systems, such as the heme pathway, from lead toxicity. Chronic exposure to methyl mercury results in increased urinary excretion of uro- and coproporphyrins in rats, mediated via inhibition of ferrochelatase and UROS and stimulation of ALAS. A tissue-specific inhibition of ALAD occurs in the kidney after treatment of rats with indium. Acute treatment of rats with nickel, platinum, tin, antimony, bismuth, and cobalt results in induction of heme oxygenase, followed by decreased microsomal heme content and ALAS stimulation in the kidney.
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PMID:Alterations in renal heme biosynthesis during metal nephrotoxicity. 332 31

Arsenic can modify the urinary excretion of porphyrins in animals and humans. Arsenic also interferes with the activities of several enzymes of the heme biosynthesis pathway, such as aminolevulinate synthase (ALA-S), porphobilinogen deaminase (PBGD), uroporphyrinogen III synthase (Uro III S), uroporphyrinogen decarboxylase (URO-D), coproporphyrinogen oxidase (COPRO-O), ferrochelatase and heme oxygenase (H-O). This review deals with HPLC-based techniques for the analysis of porphyrins in human and rodent urine and several heme enzymes with discussion on their usefulness as early biomarkers of arsenic toxicity.
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PMID:Urinary porphyrins and heme biosynthetic enzyme activities measured by HPLC in arsenic toxicity. 894 8