Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.12.7.2 (hydrogenase)
 3,522 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenal cortisol secretion is greater in female than male guinea-pigs and declines with maturation in animals of both sexes. In an attempt to determine the intra-adrenal mechanisms responsible for age and sex influences on corticosteroid output, adrenocortical enzyme activities were compared in sexually immature (3 weeks) and mature (17 weeks) animals. Adrenal mitochondrial protein concentration decreased with maturation in male and female guinea-pigs. 11beta-Hydroxylase activity in adrenal mitochondria was also lower in mature than immature guinea-pigs but greater in males than females. Neither mitochondrial cytochrome P-450 concentration nor cholesterol side-chain cleavage activity varied with age or sex. Adrenal microsomal protein concentration and 21-hydroxylase activity were similar in male and female guinea-pigs of the same age but far greater in mature than immature animals. Microsomal cytochrome P-450 concentration was unaffected by age or sex. Adrenal delta4-steroid (cortisol) hydrogenase activity increased with maturation in both male and female guinea-pigs and was higher in males than females. These observations indicate that cortisol secretion, as modified by age and sex, correlates closely with adrenal steroid reductive but not oxidative metabolism, suggesting that changes in delta4-hydrogenase activity are responsible, at least in part, for the decline in adrenal secretion during maturation in guinea-pigs.
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PMID:Changes in adrenocortical function in male and female guinea-pigs during maturation. 18 Feb 25

Spironolactone administration (50 mg/kg/day for 3 days) to make guinea pigs decreased cortisol production by adrenal slices in vitro. Adrenal microsomal and mitochondrial cytochrome P-450 levels were also decreased after treatment with spironolactone. The decline in adrenal cytochrome P-450 content was accompanied by decreases in microsomal 21-hydroxylase and mitochondrial cholesterol side-chain cleavage and 11beta-hydroxylase activities. Activities of other adrenal enzymes, such as delta4-hydrogenase and NADPH-cytochrome c reductase, were unaffected by spironolactone treatment. Cortisone administration to guinea pigs failed to mimic the effects of spironolactone on adrenal function, which indicates specificity of spironolactone action and excludes inhibition of adrenocorticotropin secretion as a mode of action. Addition of spironolactone to isolated adrenal mitochondria or microsomes produced type I spectral changes with spectral dissociation constants similar to those for endogenous steroid substrates. Spironolactone, in vitro, inhibited 11beta- but not 21-hydroxylase activity. The results indicate that spironolactone administration diminishes the activity of adrenal mitochondrial as well as microsomal cytochrome P-450-containing enzymes, resulting in a fall in corticosteroid output.
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PMID:Mechanism of action of spironolactone on adrenocortical function in guinea pigs. 97 70

We have examined the effect of recent onset diabetes on several aspects of hepatic microsomal metabolism in both streptozotocin (STZ)-induced and spontaneously diabetic BioBreeding (BB) male and female Wistar rats. Differential alterations of the diabetic state on hepatic microsomal enzyme activities were observed. Female diabetic rats exhibited no change in benzo [a]pyrene (BP) hydroxylase activity, a decrease in testosterone delta 4-hydrogenase, and an increase in aniline hydroxylase. On the other hand, male diabetic rats demonstrated a decrease in hepatic BP hydroxylase activity, no change in testosterone delta 4-hydrogenase, and an increase in aniline hydroxylase. Insulin treatment corrected these effects. No change in kidney BP hydroxylase activity was apparent in either female or male diabetics. There were no marked differences between the chemically induced and genetic models of diabetes with respect to the metabolism studies. Serum testosterone levels were significantly lower than control in male BB diabetics, whereas no change was apparent in female diabetics. Light microscopy and serum insulin determinations indicated that the spontaneously diabetic animals we examined were not severely diabetic. From electrophoresis of hepatic microsomal proteins we determined that spontaneous diabetes of short duration does alter the protein distribution in the cytochrome P-450 region. We conclude that the acute effects of STZ-induced and spontaneous diabetes on hepatic microsomal metabolism are quantitatively and qualitatively similar, despite probable differences in etiology of the diabetic state.
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PMID:Differential effects of diabetes on microsomal metabolism of various substrates. Comparison of streptozotocin and spontaneously diabetic Wistar rats. 634 6

Diabetes-induced alterations in heme and hemoproteins, as well as its relationship to drug-mediated induction of ALA Synthase (ALA-S), were examined in female Sprague-Dawley rats. Animals were rendered diabetic by a single i.v. injection of streptozotocin (STZ, 65 mg/kg) and measurements were made at various times after treatment. The basal levels of the key enzymes involved in heme synthesis, ALA-S and ALA-dehydratase (ALA-D), were decreased about 36% and 54%, respectively, 44-46 days after diabetes induction. Furthermore, the catabolism of heme that occurs via microsomal heme oxygenase progressively decreases in activity during the course of diabetes, and reaches 69% of control in 90-day diabetic animals. The basal levels of heme, cytochromes P-450 and b5 were elevated about twofold in diabetic rats as compared with their corresponding control values. The activity of benzo(a)pyrene hydroxylase in diabetic rats was also increased in proportion to the microsomal content of cytochrome P-450. In contrast, delta 4-hydrogenase, the rate-limiting enzyme in corticosterone metabolism, exhibited a 35-65% decrease in activity throughout the experimental period. Tryptophan pyrrolase activity (total, holo-, and apoenzyme) was elevated about 2.5-fold in STZ diabetic rats. In vivo insulin therapy of diabetic animals antagonized the effect of the diabetic state on the above measured parameters. Treatment with aminoglutethimide resulted in about a twofold elevation in ALA-S activity in control as well as chronically diabetic rats. However, a similar stimulatory response in ALA-S activity to CoCl2 administration was observed only in control or insulin-treated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diabetes-induced metabolic alterations in heme synthesis and degradation and various heme-containing enzymes in female rats. 660 90

Age-related changes in heme and hemoproteins, as well as the effect of testosterone treatment on these modifications were examined in male Sprague-Dawley rats. The activity of delta-aminolevulinic acid synthase (ALA-S) and the microsomal concentration of heme in aged rats were decreased by 37% and 33%, respectively, as compared to young values. In contrast, a marked increase in the activity of microsomal heme oxygenase (MHO) was seen in these animals. In aged rats, the level of cytochrome P-450 was decreased by 37%, as compared to young values. Furthermore, the activities of benzo[a]pyrene hydroxylase and aniline hydroxylase were decreased in proportion to the microsomal content of cytocyrome P-450. Steroid delta 4-hydrogenase, an index of endogenous substrate metabolism, exhibited no changes in activity during the aging process. The level of various hemoproteins such as cytochrome b5 and tryptophan pyrrolase in aged animals remained unaltered despite the decreased hepatic concentration of heme. It is worth noting that testosterone treatment of aged castrated rats restored the level of heme and cytochrome P-450 and the altered enzymatic activities of ALA-S and MHO to the "young" condition. In view of these findings, it is concluded that the events which lead to the low level of heme and cytochrome P-450 and its dependent mixed function oxidase activity during the senescent period could be due to increased rates of MHO and diminished ALA-S activities in these animals.
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PMID:Modification of age-induced changes in heme and hemoproteins by testosterone in male rats. 665 12