Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mechanism-based enzyme inactivator, alanine racemase, S-adenosylhomocysteine hydrolase, D-amino acid aminotransferase, gamma-aminobutyric acid aminotransferase, arginine decarboxylase, aromatase, L-aromatic amino acid decarboxylase, dihydrofolate reductase, dihydroorotate dehydrogenase DNA polymerase I, dopamine beta-hydroxylase, histidine decarboxylase, beta-lactamase, monoamine oxidase, ornithine decarboxylase, serine proteases, testosterone 5 alpha-reductase, thymidylate synthetase, xanthine oxidase.
 ...
PMID:The potential use of mechanism-based enzyme inactivators in medicine. 306 67

The aim of this study was to examine the inhibitory effect of the non-aromatizable androgens on FSH-stimulated aromatase activity in porcine granulosa cells. The cells were isolated from medium-sized follicles (4-6 mm) of prepubertal pigs, and cultured under chemically defined conditions in the presence of FSH (1 microgram/ml, NIADDK-oFSH-S13) with and without the androgens for an initial 48-h induction period. Subsequently, the spent medium was replaced with fresh medium containing only testosterone as substrate and the cells were reincubated for a further 6 h. The conversion of this steroid to oestradiol-17 beta during this latter 'test' period was taken as a measure of the aromatase activity. The addition of 5 alpha-dihydrotestosterone (DHT) into cultures of FSH-stimulated cells during the induction period resulted in a definite dose-dependent inhibition (30-70%) of the aromatase activity expressed in the test period. This inhibitory action, of the mixed non-competitive type, is characterized by a decrease in the apparent Vmax and an increase in the Km value, suggestive of an androgen inhibition of FSH-stimulated aromatase synthesis. This inhibition was also shown by the other 5 alpha- and 5 beta-reduced androgens: 5 beta-androstanedione was the most effective, while DHT was the least. Other steroids such as pregnenolone and progesterone were inhibitory, but testosterone and diethylstilboestrol were stimulatory. These results suggest an important mechanism for the intrafollicular control of oestrogen synthesis, involving a possible reciprocal relationship between aromatase and 5 alpha-reductase activities.
 ...
PMID:FSH-induced aromatase activity in porcine granulosa cells: non-competitive inhibition by non-aromatizable androgens. 308 93

Human placental NADPH-cytochrome P-450 reductase (EC 1.6.2.4) was purified to electrophoretic homogeneity in two chromatographic steps with a high retention of bioactivity. After solubilization with 1% sodium cholate in a protective medium containing 20% glycerol, 10 microM 4-androstene-3,17-dione, 1 mM dithiothreitol, and 0.2 mM EDTA, a 35-60% ammonium sulfate precipitate was prepared. The crude protein mixture was then applied to a 2',5'-ADP-Sepharose 4B affinity column, followed by high-performance anion-exchange chromatography (Pharmacia Mono-Q column). Two forms of the reductase were isolated. One was eluted at higher salt concentration and had a relative mass (Mr) of 79 kdaltons (kDa) as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high-performance gel permeation chromatography. A smaller size reductase with a Mr of 70 kDa, eluting at lower salt concentration, was also formed by trypsinolysis of the 79-kDa reductase. It must therefore be regarded as a proteolytic artifact. The absolute spectra in the visible region of the two reductases were identical with maxima at 376 and 452 nm, typical of a flavoprotein. They also had the same specific activity of 24.7 +/- 0.7 mumol/min per milligram protein towards cytochrome c. However, only the 79-kDa reductase showed aromatase-reconstitution activity. The homogeneity of these reductases was further confirmed by the appearance of a single peak when subjected to gradient, reversed-phase high-performance liquid chromatography. According to its amino acid composition, the 79-kDa reductase is a highly acidic and hydrophobic protein, composed of 695 residues.
 ...
PMID:Purification and properties of human placental NADPH-cytochrome P-450 reductase. 308 84

Antibodies were obtained against both protein components of the cytochrome P-450 enzyme system responsible for estrogen biosynthesis, estrogen synthetase (aromatase), from human placental microsomes. The antiserum against the NADPH-cytochrome P-450 reductase component (antiserum denoted RE-DFBIV) gave a single major band at the Mr of the authentic enzyme by immunoblotting after electrophoretic separation of SDS-solubilized microsomes and inhibited both the reductase and aromatase activities in human placental and endometrial microsomes (Tseng, L. and Bellino, F.L. (1985) J. Steroid Biochem. 22, 555-557) and in homogenates of cultured aromatase-stimulated human endometrial stromal cells and human ovarian microsomes. The antiserum against the cytochrome P-450 component of aromatase (antiserum denoted P45FBIII) also gave a single band at the Mr of the authentic protein by immunoblotting after electrophoresis, and inhibited aromatase activity in homogenates of human placental microsomes, ovarian and decidual particulate fractions and cultured aromatase-stimulated endometrial stromal cells. This antiserum had no effect on NADPH-cytochrome c reductase activity in any of the systems studied. We conclude that these antiserum preparations separately recognize the NADPH-cytochrome P-450 reductase and cytochrome P-450 components of aromatase in human placenta, ovary, decidua and endometrium. Epitopes on these aromatase component proteins involved in enzyme activity are shared among these various human tissue sources.
 ...
PMID:Antisera against estrogen synthetase from human placental microsomes. Antibody characterization and cross-reactivity studies in other organs. 311 25

Aromatase has been purified to homogeneity from human placental microsomes based on detection of its catalytic activities in the eluates from columns of octylamino-Sepharose 4B, hydroxylapatite, Mono S, hydroxylapatite HCA, and Mono Q. The purified preparation shows only one band corresponding to the apparent subunit molecular weight of 51,000 daltons on sodium dodecyl sulfate-polyacrylamide gel. The aromatase in the presence of NADPH and NADPH-cytochrome P-450 reductase converts testosterone to 17 beta-estradiol with the high specific activity of 103 nmol/min/mg of protein. However, whether the preparation is reduced by sodium dithionate chemically or by NADPH and the reductase enzymatically, its reduced, CO-difference spectrum has no peak at about 450 nm and has only a small peak at about 420 nm, probably due to its inactivation in spite of the catalytically full activity in the same preparation. The absolute spectrum of the aromatase exhibits a Soret peak at 423 nm in the absence of testosterone and addition of testosterone to the aromatase sample makes its absorption peak shift gradually from 423 to 393 nm (high spin type peak), which is a usual characteristic in the spectrum of cytochrome P-450. The reconstituted aromatase system efficiently catalyzes aromatization of 4-androstenedione, 19-hydroxy-4-androstenedione as well as testosterone. 16 alpha-Hydroxy-4-androstenedione and 16 alpha-hydroxytestosterone are also aromatized less efficiently and 19-nortestosterone is aromatized least efficiently. The reconstituted aromatase could scarcely oxidize various xenobiotics examined, suggesting a strict and narrow substrate specificity of this enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Novel properties of human placental aromatase as cytochrome P-450: purification and characterization of a unique form of aromatase. 312 18

Parturition in the pregnant sheep is preceded by an abrupt alteration in placental steroid metabolism causing a shift from progesterone to estrogen production. This change is believed to be a consequence of the prepartum rise in cortisol in the fetal circulation and involves increases in activities of the enzymes steroid 17 alpha-hydroxylase (cytochrome P-450(17)alpha), steroid C-17,20-lyase, and possibly aromatase. We have investigated the activity levels of aromatase and 17 alpha-hydroxylase in placental microsomes in late pregnancy and dexamethasone-induced labor. Over the gestational period of 118-140 days basal levels of placental aromatase were relatively constant [mean value (+/- SD) of 5.6 +/- 1.6 pmol min-1 mg microsomal protein-1 (n = 10)]. Steroid 17 alpha-hydroxylase activity was undetectable [less than 0.5 pmol min-1 mg microsomal protein-1 (n = 7)]. In six animals in labor induced with infusion of dexamethasone into the fetus, placental aromatase activity had a mean value of 14.0 +/- 2.5 pmol min-1 mg protein-1; placental steroid 17 alpha-hydroxylase, measured in four of the animals, had a mean (+/- SD) activity of 319 +/- 58 pmol min-1 mg microsomal protein-1. Immunoblotting of placental microsomal preparations with specific antibodies to cytochrome P-450(17)alpha and NADPH-cytochrome P-450-reductase indicated that the glucocorticoid-induced activity of 17 alpha-hydroxylase was associated with increased content of cytochrome P-450(17)alpha. Northern blotting with a cDNA probe for cytochrome P-450(17)alpha showed that glucocorticoid increased the levels of mRNA for the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The regulation of ovine placental steroid 17 alpha-hydroxylase and aromatase by glucocorticoid. 313 86

The kinetic properties of the testosterone-metabolizing enzymes were studied in the hypothalamus of adult and young zebra finches of both sexes. Estradiol, 5 alpha-dihydrotestosterone, 5 beta-dihydrotestosterone and 5 beta-androstane-3 alpha,17 beta-diol were identified as metabolites of testosterone in males and females at different ages between 5 days post-hatch and adulthood. During maturation, the maximum velocity (Vmax) of the aromatase and 5 beta-reductase decreased in males and females while the affinity of these enzymes for the substrate increased (decrease in km). These changes were more pronounced for 5 beta-reductase than for aromatase. The affinity change of the 5 beta-reductase occurred progressively during the post-hatching development between 5 and 30 days and is thus probably a true developmental process. In the case of the aromatase, the change in affinity occurred much later (after 30-40 days) and is thus probably related to the sexual maturation. These kinetic changes during development are directly related to the roles played by testosterone and its metabolites, in particular estradiol, in the differentiation and activation of reproductive behavior in the zebra finch. In particular, the dramatic decrease in 5 beta-reductase activity during sexual maturation should correspond to a potentiation of testosterone action in the brain.
 ...
PMID:Changes in the activity of testosterone-metabolizing enzymes in the brain of male and female zebra finches during the post-hatching period. 319 20

Sixteen dicyclohexane derivatives including the parent compound d,1-3,4-bis (4-oxocyclohexyl)-hexane (PRDX) have been synthesized and studied for putative interference with androgen binding to transport proteins, metabolizing enzymes, and receptors from rat tissues. Several of these analogues inhibited competitively the binding of dihydrotestosterone to ABP, the epididymal androgen transport protein. One compound had an affinity for ABP as high as Kd = 70 nM. Some dicyclohexanes also inhibited the aromatase enzyme which catalyses conversion of androgens into estrogens, as well as the NADPH-dependent, particulate form of 3 alpha(beta)-hydroxysteroid dehydrogenase, the enzyme that converts dihydrotestosterone into 5 alpha-androstanediol. For both enzymes the inhibition potency Ki of PRDX was about equal to the Km of the substrate. All of these interactions were specific in that they were modulated by single substitutions on the dicyclohexane molecule and they did not occur with other steroid binding proteins such as 5 alpha-reductase and the intracellular androgen receptor. A conformational study showed that dicyclohexanes can assume a 'steroidoid' conformation that differs from the crystal structure and which could account for the specific interactions with the steroid binding sites described here.
 ...
PMID:Inhibition of steroid-protein interactions by dicyclohexane derivatives. 319 13

Diagnosis of XY pure gonadal dysgenesis was established in a patient of female phenotype, with female internal genitalia, but with a chromosomal constitution of 46 XY. Streak gonads had undergone neoplastic transformation--gonadoblastoma and dysgerminoma. Before operation the concentrations of gonadotrophins in plasma were high and of oestradiol was low. Administration of oestradiol benzoate initially suppressed and then stimulated an increase in the plasma concentration of LH. These changes were not accompanied by changes in blood levels of endogenous sex steroids. A single injection of hCG failed to stimulate steroid secretion. The activities in vitro of steroid-metabolizing enzymes in the dysgenetic gonadal tissue more closely resembled those of ovarian tissue from a premenopausal and from a postmenopausal women than those in testes from two androgen-insensitive patients. However, aromatase activity was higher in the dysgenetic gonads than in the pre or post-menopausal ovaries. Examination of enzymes in genital skin fibroblasts demonstrated normal activities of 3 alpha/beta-beta-hydroxysteroid dehydrogenase and 17 beta-hydroxysteroid dehydrogenase (oxidative and reductive directions). However, 5 alpha-reductase activity was low in minces and fibroblasts of genital skin from the patient. Androgen binding was within the range for male controls.
 ...
PMID:In-vivo and in-vitro endocrine investigation of pure gonadal dysgenesis. 325 30

The in vitro inhibition of Leydig cell microsomal steroidogenesis by ketoconazole, a potent P-450 dependent enzyme blocker, was evaluated in the human, stallion and pig. Purified Leydig cells were isolated by mechanical dispersion of teased, decapsulated whole testes and sieving through a 0.25 mm stainless steel mesh. The activity of 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD), 17-hydroxylase (17-OHase), 17,20-desmolase (17,20D), 17-ketosteroid reductase (17-KSR) and aromatase were measured using a constant amount (50 microM) of 14C-labelled substrates in the presence of varying concentrations of pure ketoconazole. Products were isolated by thin layer chromatography and verified by derivative formation. 17-OHase and 17,20D activities were significantly inhibited (p less than .001) by ketoconazole at concentrations as low as 5 microM. 3 beta-HSD, 17-KSR and aromatase activities were only significantly inhibited by ketoconazole at concentrations of 500 and 5000 microM. These data describe the specific loci of inhibition of ketoconazole on testicular steroidogenesis and confirm the observations that ketoconazole is an effective inhibitor of androgen biosynthesis in several species.
 ...
PMID:The effect of ketoconazole on steroidogenesis: I. Leydig cell enzyme activity in vitro. 326 6


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>