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

Most chemical carcinogens require activation by polysubstrate monooxygenase. The phosphorylation of essential components of this cytochrome P-450 monooxygenase system, isolated from rabbit liver microsomes, cytochrome P-450 (LM2) and cytochrome reductase, was tested using two different protein kinases. One of the kinases, a cyclic AMP-independent phosvitin kinase (kinase P), was inactive in all systems tested. However, the catalytic subunit of a cyclic AMP-dependent protein kinase (kinase C) catalyzed phosphoryl group transfer to both proteins, but to different extents. Cytochrome P-450 was phosphorylated when added as sole component and also when in the presence of P-450 reductase and phosphatidylcholine. In contrast, the weak phosphorylation of P-450 reductase was reduced considerably in a complete reconstituted system containing P-450 and phosphatidylcholine. The inclusion of kinase P did not alter these results which excludes the possibility that these kinases participate in a sequential phosphorylation mechanism. The monooxygenase constituents themselves were without kinase activity. When hepatic microsomes were isolated in presence of the phosphatase inhibitor sodium fluoride no significant change in monooxygenase (7-ethoxycoumarin O-deethylation) activity was observed, whilst after preincubation with either acid or alkaline phosphatase a significant reduction in monooxygenase activity was measured. Thus, cytochrome P-450 (LM2) is phosphorylatable by protein kinase C and the catalytic activity of polysubstrate monooxygenase decreases after preincubation of microsomes with phosphatases.
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PMID:Phosphorylation of cytochrome-P-450-dependent monooxygenase components. 685 Sep 89

The endocrine regulation of the key enzyme of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34) and of the brush border enzyme alkaline phosphatase (EC 3.1.3.1) was studied in short (2 h) and long term (24 h) organ culture of rabbit ileum mucosa. In contrast to the hepatic enzyme, intestinal reductase is not subject to regulation by insulin or glucagon even at a pharmacological level. This applies to both 'total' and 'active' reductase, prepared in the absence or presence of sodium fluoride, respectively. During culture, there is a gradual, time-dependent increase in the active, dephosphorylated enzyme form. This endogenous activation was found to be unaffected by all hormones tested. Similarly, alkaline phosphatase was not influenced by both pancreatic hormones. In contrast, triamcinolone significantly (P less than 0.05) suppressed reductase in a dose-dependent fashion to 38% of controls after 24 h, but not after 2 h culture. Alkaline phosphatase was induced after both periods, but the effect was more marked after 24 h. A parallel minor stimulation of both enzyme activities was noted in the presence of 10(-9)M triiodothyronine (P less than 0.05), lower and very high (10(-5)M) concentrations were ineffective. In view of the role of glucocorticoids as intestinal growth inhibitors and of thyroid hormones as growth stimulators, it is suggested that changes in reductase reflect alterations of crypt membrane cholesterol synthesis, whereas the induction of alkaline phosphatase is mediated through an enhanced enterocyte regeneration and/or maturation.
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PMID:Hormonal regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and alkaline phosphatase in cultured intestinal mucosa. 703 2

The early effects of lithium on the kidney were studied in rats receiving a moderate daily dose (serum-Li: 0.5 to 0.8 mM per liter) for 3, 7, and 21 days. Enzyme histochemical reactions for acid and alkaline phosphatase, glucose 6-phosphatase, succinate and alpha-glycerophosphate dehydrogenase, and NADH tetrazolium reductase revealed changes confined to distal convoluted tubules and collecting ducts. The distal convoluted were unchanged at 3 days of treatment. At 7 days, a decrease in succinate dehydrogenase and NADH tetrazolium reductase and an increase in alpha-glycerophosphate dehydrogenase were noted. These changes were more conspicuous at 21 days and accompanied by tubular dilation and changes in light microscopic cellular morphology. In the collecting ducts, a cell enlargement and an increase in mitochondrial oxidative enzyme activities began to appear at 3 days, becoming more pronounced at 7 and particularly at 21 days. At 7 and even more at 21 days, a cellular hyperplasia was evident in the collecting ducts, and autoradiography after 3H-thymidine incorporation showed a marked increase in DNA synthesis in the collecting duct cells. The changes observed in the collecting ducts were most pronounced near the limit between the outer and the inner zone of the medulla. In conclusion, the rats developed morphologic changes at 3 to 7 days of treatment. The changes include (1) signs of cellular damage in the distal convoluted tubules and (2) hyperplasia and signs of increased functional activity in the collecting ducts.
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PMID:Early changes in renal distal convoluted tubules and collecting ducts of lithium-treated rats: light microscopy, enzyme histochemistry, and 3H-thymidine autoradiography. 706 26

The skin epidermis of the Teleost fish Lepadogaster candollei has been studied by cytoenzymatic methods. Besides the common epithelial cells, the epidermis is constituted of various cell types, among which are calciform cells, sacciform cells and acidophilic cells. In the cells of the basal epithelium are found hydrolytic enzymes and oxidation-reduction enzyme systems that are tied to processes of growth and cell proliferation. The positive cytoenzymatic reactions in the epithelial elements and in the glandular sacciform cells of the intermediate layers reflect their high metabolic activity. There is even more intense activity in the polygonal epithelial cells of the more superficial layers whose enzymatic machinery is characterized by high reductase and oxidoreductase activities and by alkaline phosphatase activity. These results suggest an active utilization of glucose by anaerobic and aerobic processes as well as by the pentose phosphate shunt thus suggesting the absence of the keratinization processes in the piscine skin epidermis. The cytoenzymatic findings also demonstrate that the epidermis is capable of synthesizing and elaborating materials for cell regeneration.
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PMID:Histochemical studies of some hydrolytic and oxidative enzymes in the skin epidermis of the clingfish Lepadogaster candollei Risso (Gobiesociformes, Pisces). 713 61

In vitro regulation of the key enzyme of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34) by compactin, a competitive inhibitor of the enzyme, and mevalonate was studied in rabbit ileum organ culture. Addition of compactin suppressed ileum homogenate reductase activity by over 80% at concentrations up to 0.5 microgram/ml. In contrast, compactin at the same concentrations added to the culture medium induced reductase activity up to 240% of controls. This increase was blocked by cycloheximide and mevalonolactone at 10 mM, but not by mevalonate (salt form) and cholesterol. Similarly, in contrast to ionized mevalonate, mevalonolactone significantly suppressed reductase activity of cultured intestine at 1 and 10 mM by 23 and 62%, respectively. A minor effect was also observed with preformed enzyme in fresh mucosal homogenate. When endogenous cholesterol synthesis was blocked by compactin, mucosal alkaline phosphatase activity decreased progressively, whereas medium activity from desquamated cells did not change. This distribution of the villous cell marker enzyme is characteristic of a decrease in crypt cell renewal and/or villous cell differentiation. This effect of compactin was also reversible with mevalonolactone. The reductase enzyme induced by compactin was probably latent intracellularly, since tissue cholesterol contents dropped sharply after blockade of endogenous sterol synthesis.
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PMID:Regulation of 3-hydroxy-3-methylglutaryl-CoA reductase by endogenous sterol synthesis in cultured intestinal mucosa. 722 1

Glycogen in the epithelium is interpreted as a sign of cell activity; its accumulation seems to take place gradually during cell migration. The oxido-reductase and hydrolytic enzyme-groups represent a sensitive indicator of changes in cell metabolism. The occurrence and intensity of glycogen, lactic and succinic dehydrogenases, NAD-cytochrome-c-reductase, alkaline and acid phosphatases were studied in 20 biopsy materials obtained from patients with keratotic buccal lesions. The results were compared with 20 biopsies from healthy oral mucosa. Variations were found in the localization and amount of glycogen, but no significant difference could be observed in the intensity of the oxido-reductase enzymes and alkaline phosphatase reactions. Acid phosphatase showed increased reactivity in most superficial layers of the keratinized epithelium.
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PMID:Keratotic lesions of the oral epithelium. 730 73

Ovaries of two goats with persistent corpus luteum were studied by histochemical methods. Lutein cells showed moderate alkaline phosphatase and acid phosphatase activity associated with strong delta 5-3beta-hydroxysteroid dehydrogenase and succinic tetrazolium reductase activity. The results are interpreted as an indication that the corpus luteum was functioning.
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PMID:Mucometra with persistent corpus luteum in goats. 742 41

The distribution and intensity of alkaline phosphatase deposition in 54 patients with dermatomyositis-polymyositis (PM-DM) was analyzed by the enzyme histochemical method. Increased enzyme reactivity of endomysial capillaries was found in 28% of patients, equally distributed between adult onset PM (Group I) and PM-DM with overlap in other connective tissue diseases (Group V). Patients with high endomysial capillary reactivity (R1 larger than or equal to 60) responded poorly to steroids, had an increased incidence of rheumatoid factor, and had less fiber degeneration/necrosis in their biopsies. Twenty-two percent of patients demonstrated prominent perimysial phosphatase reactivity localized in newly formed collagen and fibroblasts. Thirty patients (55%) demonstrated significant numbers of alkaline-phosphatase-positive fibers positively correlated with increased fiber degeneration/necrosis, endomysial fibrosis, increased numbers of triglyceride-containing muscle fibers, and NADH tetrazolium reductase hyperreactivity. Minimal overlap between the three enzyme distribution patterns was found. Endomysial capillary activity probably represents endothelial alkaline phosphatase induction analogous to the pattern seen normally in lower mammals (rat, rabbit, guinea pig). Alkaline phosphatase fiber reactivity probably represents a particular phase in fiber regeneration/maturation especially after denervation and is positively correlated with an increased incidence of spontaneous fibrillation potentials in PM-DM.
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PMID:Polymyositis-dermatomyositis: diagnostic and prognostic significance of muscle alkaline phosphatase. 744 98

Bone is known to be a target organ of not only estrogens, but also androgens. The mechanism by which these steroids exert their action on bone cells is still poorly understood. In the present study, the effect of 17 beta-estradiol (E2) on 5 alpha-reductase activity, converting testosterone (T) to a more potent biological androgen, dihydrotestosterone (DHT), was assessed in an osteoblast-like cell line of rat origin (UMR106-01). Cells were incubated under standardized conditions with varying concentrations of E2 (10(-12)-10(-6) M) for 48 hours. Incubation medium was replaced when the cells were preconfluent and thereafter at 24 hour intervals. Then the cells were harvested. Each cell homogenate was incubated with [4-14C]-T. DHT was detected as a single metabolite on silicagel thin layer chromatography. 5 alpha-reductase activity was determined by measuring the amount of labeled DHT from T. The radiochemical purity of DHT recovered after incubation was confirmed by recrystallization to constant specific activity. Under the conditions used, no estrogen was detected. Production of insulin-like growth factor-I and alkaline phosphatase in UMR106-01 was increased when E2 was added into the culture medium, however, 5 alpha-reductase activity was significantly decreased by the addition of 10(-12) M to 10(-6) M of E2. Maximum inhibition was noticed at 10(-10) M. Our results demonstrate that UMR106-01 cells have a capacity to transform T into the biologically more potent androgen, DHT. The result, that the enzyme activity was influenced by E2, suggests the regulatory mechanism of both sex steroids on the steroid metabolism in osteoblasts.
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PMID:[Effect of estradiol on 5 alpha-reductase activity in osteoblast-like cell (UMR106-01)]. 755 76

The membrane-anchoring subunit of Bacillus subtilis succinate:menaquinone reductase is a protein of 202 residues containing two protoheme IX groups with bis-histidine axial ligation. Residues His13, His28, His70, His113, and His155 are the possible heme ligands. The transmembrane topology of this cytochrome was analyzed using fusions to alkaline phosphatase. The results support a proposed model with five transmembrane polypeptide segments and the N-terminus exposed to the cytoplasm. Mutant B. subtilis cytochromes containing a His13-->Tyr, a His28-->Tyr, and a His113-->Tyr mutation, respectively, were produced in Escherichia coli, partially purified, and analyzed. In addition, succinate: menaquinone reductase containing the His13-->Tyr mutation in the anchor subunit was overproduced in B. subtilis, purified, and characterized. The data demonstrate that His13 is not an axial heme ligand. Thermodynamic and spectroscopic properties of the cytochrome are, however, affected by the His13-->Tyr mutation; compared to wild type, the redox potentials of both hemes are negatively shifted and the gmax signal in the EPR spectrum of the high-potential heme is shifted from 3.68 to 3.50. From the combined results we conclude that His28 and His113 function as axial ligands to the low-potential heme, which is located in the membrane near the outer surface of the cytoplasmic membrane. Residues His70 and His155 ligate the high-potential heme, which is positioned close to His13 in the protein, near the inner surface of the membrane.
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PMID:Transmembrane topology and axial ligands to hemes in the cytochrome b subunit of Bacillus subtilis succinate:menaquinone reductase. 766 65


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