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)

Hepatic microsomal heme oxygenase, the rate-limiting enzyme in heme degradation, is rapidly and markedly stimulated in selenium-deficient rats but not in controls, after a single injection of phenobarbital sodium. This stimulation occurred as early as 2 h and reached an 8- to 10-fold maximum 6 h following the drug. These observations suggest that phenobarbital rapidly and markedly enhances the degradation of hepatic heme in selenium deficiency. The cause for this rapid phenobarbital-mediated stimulation of heme degradation was investigated. It could not be ascribed to either accelerated turnover of cytochrome P-450, or enhanced lipid peroxidation possibly resulting from the concomitant lack of glutathione peroxidase in selenium deficiency. For these reasons, the metabolism of hepatic heme in the selenium-deficient rat liver was further examined during the 6-h period following phenobarbital. These studies indicated that whereas heme was synthesized much faster and to a greater extent in the selenium-deficient rat liver than in the control, its utilization in the formation of hemoproteins such as cytochrome P-450 and tryptophan pyrrolase was apparently impaired in selenium deficiency. Such defective utilization of heme in the 6-h period following phenobarbital could effectively result in a relative excess of unutilized "free" heme; hence the consequent stimulation of microsomal heme oxygenase for its disposal.
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PMID:Rapid stimulation of hepatic microsomal heme oxygenase in selenium-deficient rats. An effect of phenobarbital. 68 48

1. The utilization of haem by rat liver apo-(tryptophan pyrrolase) under basal conditions and after enhancement of the enzyme activity by various mechanisms was studied under the influence of treatments affecting various aspects of liver haem metabolism. 2. These treatments were: benzoate and p-aminobenzoate as substrates of glycine acyltransferase, acetate as an inhibitor of 5-aminolaevulinate synthase activity, enhancement of 5-aminolaevulinate dehydratase by aluminium, destruction of haem and inhibition of ferrochelatase by porphyrogens, increased haem utilization by phenobarbitone and enhancement of haem oxygenase activity by metal cations. 3. The results show that the haem saturation of the apoenzyme is sensitive to all these treatments. 4. The possible usefulness of tryptophan pyrrolase in studying the regulation of liver haem is suggested.
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PMID:The effects of acetate, metal cations, phenobarbitone, porphyrogens and substrates of glycine acyltransferase on the utilization of haem by rat liver apo-(tryptophan pyrrolase). 88 Feb 48

Endotoxin was administered to rats at a dose shown previously to stimulate hepatic haem oxygenase activity and to block induction of delta-aminolaevulinate synthase, apparently by causing redistribution of haem from cytochrome P-450 to a regulatory haem pool in the liver. Within 5h of the administration of endotoxin (at a time when the effect of the compound on cytochrome P-450 is maximal) the relative saturation of tryptophan pyrrolase with intrinsic haem rose, from a basal value of 50% to 90%, indicating that 'free' haem had become available. Concurrently, the activity of delta-aminolaevulinate synthase was decreased to 25% of its basal value. Haem oxygenase reached peak activity 13h after endotoxin administration. These findings provide new evidence for the existence of an 'unassigned' hepatic haem fraction, which exchanges with cytochrome P-450 haem and regulates these three enzyme functions.
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PMID:Effect of endotoxin on tryptophan pyrrolase and delta-aminolaevulinate synthase: evidence for an endogenous regulatory haem fraction in rat liver. 91 21

Metalloporphyrin inhibitors of heme oxygenase may also have photosensitizing properties in vivo. To assess photoactivity in serum, the relative ability to mediate photooxidation of tryptophan or other oxidizable targets, presumably by singlet oxygen production, was measured for tin mesoporphyrin, zinc mesoporphyrin, and zinc deuteroporphyrin bisglycol in aqueous solution and when bound to human serum albumin. While tin mesoporphyrin sensitized at the greatest initial rate in aqueous solution, the zinc compounds sensitized at a greater initial rate in detergent micelles or when bound to albumin. There was minimal alteration of the tin mesoporphyrin during the time course of illumination in the Soret or visible absorption regions. The zinc compounds, however, proved to be extremely photolabile and were extensively destroyed by light; the photooxidized forms were found to be ineffective as inhibitors of heme oxygenase.
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PMID:Comparative photoactivity of tin and zinc porphyrin inhibitors of heme oxygenase: pronounced photolability of the zinc compounds. 178 Mar 55

The effects of exogenous heme on the activity of delta-aminolevulinate synthase, heme oxygenase, tryptophan-2.3-dioxygenase and microsomal cytochrome content in rat liver were studied. It was shown that hemin chloride diminishes the delta-aminolevulinate synthase activity and provokes heme oxygenase induction. This is paralleled with the induction of the tryptophan 2.3-dioxygenase apoenzyme and an increase in the saturation of the enzyme with heme. The cytochrome b5 content does not change thereby, whereas that of cytochrome P-450 shows a decrease. Upon combined administration of actinomycin D and hemin the cytochrome P-450 level is markedly increased. Actinomycin D by itself has no effect on the hemoprotein concentration. It is concluded that the increase in the cytochrome P-450 level results from the activation of heme-induced mRNA translation.
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PMID:[The role of heme in the regulation of tryptophan-2,3-dioxygenase activity and content of cytochrome P-450 in rat liver]. 260 73

The activity of key enzymes of heme metabolism (delta-aminolevulinate synthase, EC 2.3.1.37, and heme oxygenase, EC 1.14.99.3) and the content of some hemoproteins were examined in the liver of male Wistar rats aged 1, 3 and 24 months. It is established that the activity of delta-aminolevulinate synthase decreases when rats reach the age of 3 months and remains at the same level in rats aged 24 months. The content of microsomal cytochrome P450 and the activity of tryptophan-2,3-dioxygenase holoenzyme increase when rats reach the age of 3 months. The total tryptophan-2,3 dioxygenase activity is higher in animals aged 24 months as compared to those aged 1 month. The heme oxygenase activity and the content of microsomal cytochrome b5 do not change with age.
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PMID:[Activity of key enzymes of heme metabolism and the content of several hemoproteins in the liver of rats of various ages]. 274 Dec 45

The presence of heme oxygenase and NADPH cytochrome P-450 (c) reductase, the latter an integral component of heme oxygenase and cytochrome P-450-dependent drug metabolizing enzymes, was demonstrated in human corneal epithelium. We reported for the first time that human corneal epithelium contains heme oxygenase activity as high as 20% of that reported for the human liver. Using immunological techniques, we demonstrated that heme oxygenase proteins from human cornea and liver are very similar; both have a molecular weight of 32,000 as demonstrated by Western blot analysis. We also studied the presence of NADPH cytochrome P-450 (c) reductase. The human corneal epithelium contains significant amount of NADPH cytochrome P-450 (c) reductase activity, and this corneal protein is similar to the known liver protein; both have a molecular weight of 71,000 and react with antibodies prepared against purified liver NADPH cytochrome P-450 (c) reductase. As the heme oxygenase system is the rate limiting step in heme degradation, this system plays a pivotal role in regulation of cellular heme in corneal epithelium, thus modulating the activity of hemoproteins such as catalase, tryptophan pyrrolase and thromboxane synthetase.
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PMID:Presence of heme oxygenase and NADPH cytochrome P-450 (c) reductase in human corneal epithelium. 311 66

In the present study, we investigated the contribution of methylsulfonyl metabolites derived from m-dichlorobenzene (m-DCB) on the heme metabolic enzyme induction by the parent compound in rats. The time courses of the effects of a single ip administration of m-DCB (200 mg/kg, 1.36 mmol/kg) and 2,4- and 3,5-dichlorophenyl methyl sulfones (2,4- and 3,5-DCPSO2Mes) (each 50 mumol/kg) on hepatic microsomal cytochrome P450 content were almost in parallel with those on the total heme content in liver microsomes. m-DCB significantly increased the heme oxygenase activity, but 2,4- and 3,5-DCPSO2Mes did not. On the other hand, m-DCB and both methyl sulfones markedly enhanced the delta-aminolevulinic acid (ALA) synthetase activity. No change was observed in percentage saturation of the tryptophan pyrrolase activity after administration of m-DCB, whereas this ratio at 6 hr after injection of 3,5-DCPSO2Me was increased. In the liver of the DL-buthionine-(S,R)-sulfoximine (BSO)-treated rats dosed with m-DCB, both of 2,4- and 3,5-DCPSO2Mes were present at significantly lower concentrations than in non-BSO-treated rats. Additionally, the m-DCB did not elevate the ALA synthetase activity in the BSO-treated rat. On the other hand, the administration of either 2,4- or 3,5-DCPSO2Mes to BSO-treated rats resulted in induction of ALA synthetase. m-DCB and 2,4- and 3,5-DCPSO2Mes produced a dose-related increase in liver levels of methyl sulfones. The changes in the ALA synthetase activity after the administration of varying doses of m-DCB were similar to those after the administration of 2,4- or 3,5-DCPSO2Mes, whereas the sum of the concentration of two methyl sulfones in the liver of rats dosed with m-DCB was almost the same as the concentration of methyl sulfone after the administration of either 2,4- or 3,5-DCPSO2Mes. The results strongly suggest that the methyl sulfones derived from m-DCB, i.e., 2,4- and 3,5-DCPSO2Mes, contribute highly to the induction of the ALA synthetase activity by the parent compound.
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PMID:Contribution of methylsulfonyl metabolites of m-dichlorobenzene to the heme metabolic enzyme induction by the parent compound in rat liver. 320 31

Acute arsenic (As) administration produced in rat liver a decrease in the heme saturation of tryptophan pyrrolase (TP), accompanied by dose-related increases in 5-aminolevulinate synthetase (ALAS) and heme oxygenase (HO) activities, along with a corresponding decrease in cytochrome P-450 (P-450) concentration. The relationship between heme synthesis and degradation was altered as a result of As treatment. The magnitude of these effects was related to the oxidation state of arsenic, sodium arsenite (AsIII) being more potent than sodium arsenate (AsV). These results support the contention that the heme saturation of TP is sensitive to treatments that modify liver heme concentration. The increase in HO activity produced by As appears to be mediated by a mechanism largely or entirely independent of heme. The main effects of continuous exposure to AsIII were an initial decrease in the heme saturation of TP, which remained constant during the period of treatment, and an initial increase in ALAS activity, which after ten days of exposure dropped somewhat but remained above control values. No significant effects on HO or P-450 concentration were observed. These results were interpreted as indicative that a new balance between heme synthesis and degradation had been reached and that an adaptive response to the subchronic effects of AsIII was taking place.
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PMID:Assessment of arsenic effects on cytosolic heme status using tryptophan pyrrolase as an index. 323 42

The effect of a single dose of benzene (0.5 ml/kg body wt i.p.) on the heme saturation of tryptophan pyrrolase activity in liver was examined. There was a significant decrease in the heme saturation of hepatic tryptophan pyrrolase, suggesting depletion of "regulatory heme". After benzene administration there was significant increase in delta-aminolevulinate (ALA) synthetase activity (approx. 2-fold) while delta-aminolevulinate dehydratase activity was significantly decreased, however, ferrochelatase and heme oxygenase activities were unaltered. Administration of tryptophan to benzene pretreated rats showed a reversal of benzene effects on heme synthesizing enzymes: there is an increase in the heme saturation of tryptophan pyrrolase and decrease in delta-aminolevulinate synthetase. However, there was no significant alteration in the activity of delta-aminolevulinate dehydratase.
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PMID:Depletion of liver regulatory heme in benzene exposed rats. 334 24


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