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)

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

Previous studies have established that the effects of estradiol (E2) on hepatic steroid and drug metabolism are demonstrable only in the presence of the pituitary gland. Studies were carried out to test the hypothesis that GH is the pituitary feminizing factor mediating the actions of E2 on hepatic metabolism. E2 and GH administered to castrated male rats had similar effects on hepatic enzymes, decreasing the oxidataive metabolism of drugs [ethylmorphine demethylation, aniline, hydroxylation, and benzo(a)pyrene hydroxylation) and increasing steroid (corticosterone) delta 4-hydrogenase activity. None of these effects of E2 or GH could be demonstrated in hypophysectomized (hypox) rats. However, GH administration to T4- or ACTH-treated hypox rats resulted in some of the changes in drug and steroid metabolism seen in animals with intact pituitary glands. The actions of GH on hepatic microsomal enzymes were fully demonstrable in hypox rats receiving both T4 and ACTH. E2 had no effects in T4 plus ACTH-treated hypox rats. These and prior observations are consistent with the hypothesis that GH mediates the actions of E2 on hepatic microsomal drug- and steroid-metabolizing enzymes. The data also indicates that the cations of GH on hepatic metabolism are dependent upon the interactions with still other endocrine factors.
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PMID:Is growth hormone the pituitary feminizing factor mediating the actions of estradiol on hepatic drug and steroid metabolism? 677 28

The guinea pig adrenal increases in the size with age, yet cortisol secretion per gram adrenal declines. It has been suggested that this could be due to catabolism of cortisol by increased adrenal delta 4-hydrogenase. In this paper we show that delta 4-hydrogenase is localized in the zona reticularis and increases coincidently with the large increase in the volume of this zone with age. Glands were microdissected to give inner vs. outer cortices, and the postmitochondrial supernatants of these two portions were assayed for delta 4-hydrogenase activity. The enzyme was found almost solely in preparations from inner cortices, which were predominantly zona reticularis. Cells were isolated from each portion and assayed for delta 4-hydrogenase activity. Again, only those which contained zona reticularis cells, that is, those from the inner cortices, had activity. The activity was shown to be present in both microsomes and cytosol, although the latter was preferentially expressed in a 15,000 X g supernatant. When the metabolites were separated by thin layer chromatography, the products of the microsomal enzyme were 5 alpha- and 5 beta-dihydrocortisol (1:1) and that of the cytosolic enzyme was 5 beta-dihydrocortisol, whereas in the 15,000 X g supernatant the 5 beta-isomer was the predominant product. Its identity as 5 beta-dihydrocortisol was confirmed by mass spectroscopy. Tetrahydrocortisol comprised a minor portion of the products.
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PMID:delta 4-Hydrogenase in guinea pig adrenal: evidence of localization in zona reticularis and age-related change. 707 35


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