Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:Q8NEX9 (reductase)
26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Unlike the normal liver, numerous transplantable rodent and human hepatomas are unable to alter their rate of sterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-GoA) reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34] activity in response to a dietary cholesterol challenge. It has been suggested that this metabolic defect is linked to the process of malignant transformation. Hepatoma 7288C "lacks" feedback regulation of cholesterol synthesis when grown in vivo but expresses this regulatory property when grown in vitro (then called HTC). Therefore, it was used as a model system to answer whether an established hepatoma cell line that modulates its rate of cholesterol synthesis in vitro can express this property when grown in vivo, and whether cells reisolated from the tumor mass have the same regulatory phenotype as before transplantation. Our results show that long-term growth of hepatoma 7288C in tissue culture has not caused a biotransformation that permits feedback regulation of HMG-CoA reductase when the cells are transplanted back into host animals. In addition, HTC cells reisolated from the tumor mass and established in tissue culture continue to have the ability to regulate HMG-CoA reductase activity. Therefore, malignant transformation is not categorically linked to the loss of the cellular components necessary to regulate sterol synthesis and HMG-CoA reductase activity.
...
PMID:Comparison of regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in hepatoma cells grown in vivo and in vitro. 18 7

The concentrations of cytochrome P-450 and the activities of aryl hydrocarbon [benzo(a)pyrene] hydroxylase (AHH) and reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase were measured in early (gray-white) and remodeled (brown) hyperplastic nodules induced in the livers of rats with 2-acetylaminofluorene and were compared to the values in control livers and in the liver surrounding the nodules. Cytochrome P-450 content of early (14 weeks) hyperplastic nodules is 30% of the activity of untreated control livers and 48% of the activity of the surrounding liver. AHH activity of the early nodules is 10% of the control activity and 33% of the activity in the surrounding nonnodular liver. Nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity in the microsomes of early nodules is 76% of the control activity and 78% of the activity in the surrounding liver. In the late remodeled nodules, (22 and 25 weeks), the cytochrome P-450 content is 40% of that of controls and AHH activity is 15% of the control activity. In primary hepatomas induced by 2-acetylaminofluorene, cytochrome P-450 content is 21% of that of controls, AHH activity is 11% of the activity of controls, and reductase is 50% of the control activity. These results, indicating a relative nodule deficiency in some of the cellular components believed to be important in the activation of hepatocarcinogens and hepatotoxins, offer one possible explanation for the relative resistance to carcinogen cytotoxicity of hyperplastic liver nodules.
...
PMID:A relative deficiency of cytochrome P-450 and aryl hydrocarbon [benzo(a)pyrene] hydroxylase in hyperplastic nodules induced by 2-acetylaminofluorene in rat liver. 18 17

HMG CoA reductase, which catalyzes the reaction, HMG CoA + 2 NADAPH2 leads to mevalonate + CoA-SH + 2 NADP, is considered to be the rate-limiting enzyme on cholesterol biosynthetic pathway. Since a degree in activity of this enzyme is almost proportional to the rate of cholesterol synthesis from acetate, elucidation of factors that regulate reductase activity would provide insight into the control mechanisms on the cholesterol biosynthesis. In the present study, attempts were made to establish standard assay conditions of HMG CoA reductase activiy, and to qualify the factors affecting the activity of the enzyme. The results obtained were as follows: (1) As standard assay conditions of HMG CoA reductase activity, 85, muM were chosen for substrate concentration, 25-80 mug for microsomal enzyme protein, and 20 min for incubation time in a final volume of 0.1 ml. (2) HMG CoA reductase activity of rat liver microsomes was exhibited diurnal variation. The level of reductase activity at night was 4 fold higher than that of at daytime. (3) Either ATP or insulin administration stimulated hepatic HMG CoA reductase activity. But, cyclic AMP had no effect on reductase activity. The stimulatory effect of ATP or insulin on reductase activity was inhibited by a preadministration of glucagon. These results suggested that an interplay of hormone might regulate reductase activity and consequently cholesterol biosynthesis. (4) HMG CoA reductase activity was increased by preincubation of microsomes with cytosol. Presence of ATP or Mg++ intensified this effect. When digested by trypsin or degenerated by heat treatment, cytosol lost the stimulating activity. These results suggested as existence of protein factors in cytosol, which might modulate the enzyme interconversion from inactive to active forms.
...
PMID:[Studies on the regulatory factors of 3-hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) activity]. 18 33

Cytochrome c immobilized on cyanogen bromide-activated Sepharose 4B may be used to study photochemical reactions in chloroplasts. Chloroplast reduction of both immobilized and soluble forms of the cytochrome occurs along the exogenous and endogenous pathways which results in a weaker reduction of the immobilized protein as compared to that of the soluble one. The time of the reduced immobilized cytochrome c oxidation in the dark is two orders of magnitude greater than that of the soluble one. This fact may be interpreted in terms of spatial dissociation of reductase and oxidase centers of chloroplasts with reference to the cytochrome. The optimal ionic strength for cytochrome reduction, i.e. ionic strength causing an in vitro destruction of the ferredoxin-NADP-reductase complex was found to equal to 0.2 M.
...
PMID:[Cytochrome c immobilized on Sepharose 4B and its participation in photochemical reactions of chloroplasts]. 19 41

Metabolic control associated with diauxic growth of Pseudomonas oxalaticus in batch cultures on mixtures of formate and oxalate was investigated by measuring intracellular enzyme and coenzyme concentrations and QO2 values during transition experiments from oxalate to formate and vice versa. In transition from oxalate to formate oxalyl-CoA reductase concentration declined after the exhaustion of oxalate and ribulose-1,5-diphosphate carboxylase and 14CO2 fixation appeared upon addition of formate. In the reciprocal transition, ribulose-1,5-diphosphate carboxylase and 14CO2 fixation rate declined sharply after formate exhaustion, and oxalyl-CoA reductase appeared only after addition of oxalate. The intracellular NAD and NADP concentrations measured in the same experiments are reported. At substrate exhaustion the proportion of NAD in the reduced form fell from 15-20% to 2%. On addition of formate to an oxalate-starved culture there was an immediate increase in the proportion of NADH to 50%; such an increase was not observed in the reverse experiment.
...
PMID:Metabolic regulation in Pseudomonas oxalaticus OX1. Enzyme and coenzyme concentration changes during substrate transition experiments. 20 39

A study was made of the inhibitors of the adrenal gland function and ACTH on the activity of NADP-specific glutathionreductase in the adrenal glands and the liver of dogs. After a 10-day feeding to dogs of o,p'-dichlordiphenyldichlorethane (o,p'-DDD) and p,p'-diethyldiphenyl dichlorethane (p,p'-pertane) in a dose of 50 mg/kg there was observed a marked activation of glutathion reductase in the adrenal glands. Elevation of the activity of the enzyme was revealed as soon as 24 hours after the administration of o,p'-DDD. The inhibitors under study failed to influence the activity of the enzyme in the liver of dogs, this indicating a specific action of o,p'-DDD and pertane on the adrenal gland cortex. Stimulation of glucocorticoid biosynthesis under the effect of ACTH administered once in a dose of 25 Units/kg was not accompanied by the changes in the activity of glutathione reductase in the adrenal glands and the liver of dogs. Prolonged ACTH administration (4 Units/kg) caused a significant reduction of the enzyme activity calculated as per 1 mg of protein in the adrenal gland homogenate.
...
PMID:[Activity of glutathione reductase in the adrenal glands and the liver of dogs after administration O,P-DDD, perthane and ACTH]. 20 22

Purple bacteria Rhodospirillum rubrum and Thiocapsa roseopersicina form two enzymes, hydrogenase and nitrogenase, which participate in hydrogen metabolism. H2 photoproduction in these bacteria is associated mainly or completely with the action of nitrogenase. The soluble and membrane-bound hydrogenases of T. roseopersicina have similar physicochemical properties (mol. weight, subunit composition, N-terminal amino acids, Fe2+ and S2- content, pl. Eo'). In comparison with other hydrogenases the enzyme from R. rubrum and T. roseopersicina evolve H2 with high rate from reduced cytochrome c3, but not from ferredoxins. H2 production and N2 fixation take place in the presence of NAD(P)H. NADP-reductase, ferredoxin and cytochrome c3 participate in this reaction. Possible relationships between hydrogenase-nitrogenase in the metabolism of molecular hydrogen are discussed.
...
PMID:Relationships in hydrogen metabolism between hydrogenase and nitrogenase in phototrophic bacteria. 20 59

Depression of the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase [mevalonate:NADP(+) oxidoreductase (CoA-acylating); EC 1.1.1.34] was elicited by the removal of serum from the growth medium of HeLa S3G cells with a concomitant expected increase in cellular sterol biosynthesis; if dexamethasone (9alpha-fluoro-11beta,17alpha,21-trihydroxy-16alpha-methyl-1, 4-pregnadiene-3,20-dione) was present in the serumless medium, there was an augmentation of HMG-CoA reductase activity but a suppression of sterol biosynthesis. When human serum, human low density lipoprotein, or calf serum was present in the medium, there was a reduction of both the enzyme activity and sterol biosynthesis, but the presence of dexamethasone resulted in an increase in HMG-CoA reductase activity as compared to the controls containing human serum, low density lipoprotein, or calf serum alone. In contrast, either low density lipoprotein or whole serum supplementation eliminated the differences in acetate incorporation into sterols between glucocorticoid-treated and untreated cells. Human high density lipoproteins had little effect on the enzyme activity and abolished the difference in sterol biosynthesis only at relatively high concentrations. Addition of low density lipoproteins to cells after preincubation in serumless medium elicited the same rate of decay of HMG-CoA reductase (t(1/2) 3.8-4.2 hr) regardless of the presence of glucocorticoids in the medium, but there was an exaggerated lag before the onset of suppression in the hormone-treated cells. If free cholesterol was present in the medium, the dexamethasone augmentation of HMG-CoA reductase was maintained, but the addition of either 7-ketocholesterol or 25-hydroxycholesterol abolished the difference between glucocorticoid-treated and control cells. These observations suggest that, under certain physiological conditions, HMG-CoA reductase activity no longer accurately reflects cellular sterol biosynthesis.
...
PMID:Regulation of cholesterol biosynthesis in HeLa S3G cells by serum lipoproteins: dexamethasone-mediated interference with suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase. 20 49

The free and esterified cholesterols of plasma low density lipoprotein (LDL) were extracted with heptane and replaced with 25-hydroxycholesteryl oleate. The resulting particle, designated r-[25-HC oleate]LDL, bound to LDL receptors on human fibroblasts, was taken up by adsorptive endocytosis and was hydrolyzed in lysosomes in a manner similar to that of native LDL. The r-[25-HC oleate]LDL suppressed 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate:NADP(+) oxidoreductase (CoA-acylating), EC 1.1.1.34], the enzyme catalyzing the rate-limiting step in cholesterol biosynthesis. This suppression did not occur when lysosomal hydrolysis of r-[25-HC oleate]LDL was inhibited by chloroquine. When fibroblasts were incubated with r-[25-HC oleate]LDL in the absence of a source of cholesterol, the cells developed an abnormal morphology, their growth was inhibited, and the cells died. The toxic effects of r-[25-HC oleate]LDL were prevented when the growth medium was supplemented with cholesterol in ethanol or with mevalonate, the product of the reductase reaction. These data suggest that the toxicity of r-[25-HC oleate]LDL was due to its suppression of reductase, which in turn caused cellular cholesterol deficiency. The r-[25-HC oleate]LDL did not suppress reductase activity nor did it alter the growth or morphology of mutant fibroblasts lacking LDL receptors, which were obtained from a patient with homozygous familial hypercholesterolemia. These experiments demonstrate the feasibility of using reconstituted LDL to selectively deliver hydrophobic compounds other than typical cholesteryl esters to cells possessing LDL receptors.
...
PMID:Receptor-mediated uptake of low density lipoprotein reconstituted with 25-hydroxycholesteryl oleate suppresses 3-hydroxy-3-methylglutaryl-coenzyme A reductase and inhibits growth of human fibroblasts. 21 11

The microsomal flavoprotein, NADPH-cytochrome c reductase, has been reexamined to determine: (1) the nature of the flavine bound to the enzyme and (2) the oxidation-reduction state of the "half-reduced" form of the flavoprotein. Iyanagi and Mason (Iyanagi, T., and Mason, H.S. (1973), Biochemistry 12, 2297) have recently proposed that NADPH-cytochrome c reductase contains both FAD and FMN as prosthetic groups in lieu of FAD as the sole constituent, as suggested by all previous studies of this enzyme. The data presented herein, utilizing the recently published fluorometric procedure of Faeder and Siegel (Faeder, E. J., and Siegle, L. M. (1973), Anal. Biochem. 53, 332) for the determination of FAD and FMN in mixtures, confirm the conclusions of Iyanagi and Mason for both rat and pig liver reductase preparations. Data for other flavoproteins are also presented. Iyanagi and Mason have also concluded that the air-stable "semiquinone" is a form of NADPH-cytochrome c reductase reduced by one electron per two falvines (F-FH). The present studies, however, do not agree with this conclusion, but instead support our previous results which indicate that both the aerobic and anaerobic half-reduced states of this flavoprotein exist in the two-electron reduced form (FH-FH). Removal of NADP+ does not affect the spectrum of the air-stable half-reduced form of the flavoprotein, nor does it affect the back titration of this intermediate by potassium ferricyanide. The possible implications of these observations on the catalytic cycle of the flavines of NADPH-cytochrome c reductase are discussed.
...
PMID:Properties of the stable aerobic and anaerobic half-reduced states of NADPH-cytochrome c reductase. 23 49


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

---