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)

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase, E.C. 1.1.1.34), the major rate-limiting enzyme of the sterol biosynthetic pathway, was studied in ileal epithelial cells isolated in a villus-to-crypt gradient according to Weiser (Weiser, M. M. 1973. J. Biol. Chem, 248:2536-2541). Alkaline phosphatase (E.C. 3.1.3.1) served as a marker for the mature villus cells. Protease effects on activity determinations were negligible. The intracellular location of HMG-CoA reductase could not be precisely determined. The activity of ileal reductase was predominantly associated with the less differentiated lower villus and crypt cells, while the reverse gradient occurred with alkaline phosphatase. This distribution of enzymes persisted in both fed and fasted rats injected with control saline-phosphate, although fasting decreased total reductase units in the ileum by 86% in 72 hr. Treatment with cholestyramine and with 4-aminopyrazolo[3,4-d]pyrimidine (APP) enhanced reductase activity in ileal cells. The percent stimulation in both cases was higher in the upper villus cells than in the crypt cells, leading to abolition of the gradient in enzyme activity. However, APP treatment caused a 98% loss in total alkaline phosphatase units and a 55% loss in total epithelial cell protein in 72 hr. Thus, there was no increase in total reductase units. These data show that APP affects ileal cell metabolism directly. Furthermore, it appears that the regulation of sterol synthesis in the intestinal mucosa, via HMG-CoA reductase, involves a complex interplay of the effects exerted by the level of alimentation, the enterohepatic circulation of bile, and the levels of plasma lipoproteins.
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PMID:Distribution of 3-hydroxy-3-methylglutaryl coenzyme A reductase and alkaline phosphatase activities in isolated ileal epithelial cells of fed, fasted, cholestyramine-fed, and 4-aminopyrazolo[3,4-d]pyrimidine-treated rats. 49 57

In the paper we observed histochemically the distribution and activity of 16 enzymes in the normal rat gastric mucosa. The lysosomal enzymes were demonstrated by the method of semipermeable membranes (LOJDA 1972). At the proof of dehydrogenases aqueous and gel media were used. The parietal cells of the gastric mucosa contained a moderate activity of acid phosphatase, E-600 resistant esterase, and only a very slight activity of beta-glucuronidase and N-acetyl-beta-D-glucosaminidase. The macrophages of the interstice contained a high activity of beta-glucruonidase, acid phosphatase, E-600 resistant esterase and a low activity of N-acetyl-beta-D-glucosaminidase. The chief cells of the rat gastric mucosa, in contrast to the human, did not contain nonspecific esterase and also in them acid phosphatase was mostly lacking. The alkaline phosphatase was found only in the endothelium of the capillaries of the gastric mucosa. The parietal cells contained high activities of succinate dehydrogenase, alpha-glycerophosphate dehydrogenase, beta-hydroxybutyrate dehydrogenase, NADH tetrazolium reductase, a lower activity of NADPH tetrazolium reductase, as well as other soluable dehydrogenases. At the examination of dehydrogenases using aqueous as well as gel media with PMS during optimal short incubation periods, we found more and less active forms of parietal cells. The different oxidoreductase capacity of parietal cells in normal rat gastric mucosa can point to their unequal-functional load at the production of hydrochloric acid. The findings obtained are compared with the findings in older papers concerning different experimental animals and with the distribution of enzymes in the human gastric mucosa.
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PMID:Histochemical localization of enzymes in the normal rat gastric mucosa using the technique of the semipermeable membranes and the other methods. 82 7

The localization of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase, E.C. 1.1.1.34) in the villous and crypt cells of the small intestine was accomplished after separating these cells from the mucosal layer by sequential dissociation in a "dual-buffer" system. Consistent separation was demonstrated by using the marker enzymes alkaline phosphatase, specific to the villous cell, and thymidine kinase, specific to the crypt cell. Cells obtained were 95-100% viable, and no relative difference in lability was observed, as evidenced by the equal distribution of acid phosphatase. This method of cell separation was an improvement over the "scraping" technique which damaged cells severely and produced villous preparations that contained little or no reductase activity. The HMG-CoA reductase specific activity in whole cell homogenates of the ileal villi was 0.47 and of the crypts was 0.27 nmol/min per mg of protein, considerably higher values than have been reported earlier. Also in comparison to the crypts, the villi incorporated 1.5-fold more [(14)C]-acetate into sterols, a ratio similar to that describing the distribution of HMG-CoA reductase in the two cell populations. These results unequivocally establish that the villi have higher HMG-CoA reductase activity than the crypts and confirm an earlier report from this laboratory that the villi are a major site of sterol synthesis. The sterol bio-synthetic capacity of the small intestine was highest in the ileum and decreased towards the jejunum. The HMG-CoA reductase specific activity of the ileum averaged 0.30 and that of the jejunum 0.10 nmol/min per mg of protein; however, the cholesterol content of the ileum was slightly lower than the jejunum. These results are discussed to suggest the possibility that the sterol content of the ileum may largely be due to in situ synthesis.
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PMID:3-Hydroxy-3-methylglutaryl coenzyme A reductase in isolated villous and crypt cells of the rat ileum. 92 17

Subcellular distribution study of cytoplasmic organelles was performed on human polymorphonuclear leukocytes after homogenization in 0.34 molar sucrose by differential centrifugation and sucrose density gradient centrifugation of the homogenate. The whole homogenate and each fraction was assayed for nitroblue tetrazolium (NBT)-reductase with and without 1 mM potassium cyanide, and the distribution of this enzyme was compared to the distribution of lysozyme, peroxidase, beta-glucuronidase, and acid and alkaline phosphatase. Enzyme recovery was 97 per cent and ranged between 74 and 124 per cent. Latent activity of all enzymes except NBT-reductase, acid, and alkaline phosphatase was demonstrated by observing a four- to sixfold increase in activity after the addition of Triton-X 100. Maximal relative specific activity using either DPNH or without cyanide for NBT-reductase was found in the 100,000 x g differential centrifugation fraction and was concentrated in the less dense top fraction of the sucrose density gradient. The distribution pattern was similar to acid and alkaline phosphatase. In contrast, the maximal concentration of beta-glucuronidase and peroxidase was found in the heavier 7,200 x g granule fraction and in the more dense bottom fractions of the sucrose density gradient. Maximal lysozyme activity was concentrated in the 30,000 x g granule fraction and in the fractions located between the heaviest and lightest fractions of the sucrose density gradient. The lack of latent activity and the similarity of subcellular distribution of NBT-reductase to acid and alkaline phosphatase, two enzymes associated with microsomes and plasmalemal membranes in human polymorphonuclear leukocytes (PMN), indicates that NBT-reductase is also a nonlysosomal enzyme located in microsomes or in plasmalemal membranes. These findings support the previously described histochemical observations that initial reduction of NBT to formazan occurs on the PMN plasmalemal surface membrane at the point of particle attachment. In addition, they suggest that alteration of the surface membrane of the PMN by particle attachment or other surface forces may activate NBT-reductase, leading to an accumulation of formazan in the region of the altered membrane as the phagocytic vacuole is formed.
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PMID:Subcellular distribution of nitroblue tetrazolium reductase (NBT-R) in human polymorphonuclear leukocytes (PMN). 118 38

This study observed the effect of Gu Chi Wan on the enzyme histochemistry changes of diabetic rats with experimental periodontal disease. The results indicate that the experimental group has not the decrease of oxidase-reductase and alkaline phosphatase as seen in control group and demonstrate the protective effect of Gu Chi Wan perhaps acts through regulating metabolism of periodontium of rats with experimental periodontal disease, and then improving the immune response of the host.
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PMID:[The effect of gu chi wan on enzyme histochemistry changes in diabetic rats with experimental periodontal disease]. 128 94

Gastric mucosal PG E2 receptors are the common antisecretory working point of all prostanoid types and may also be involved in "protective" effects. We investigated the subcellular localization of these receptors, as measured by displaceable 3H-PG E2 binding, and identified different organelles by monitoring the activities of specific marker enzymes. Porcine mucosal homogenates were subdivided by differential centrifugation into fractions P1 (1000 x g), P2 (20,000 x g), P3 (300,000 x g) and the supernatant S1. P3 was further fractionated over a series of sucrose step gradients. Mitochondria and lysosomes were enriched in P2 (maximum specific activities of cytochrome-c-oxidase of beta-glucosidase, beta-glucuronidase, beta-galactosidase, respectively). Plasma membranes (alkaline phosphatase, gamma-glutamyl-transpeptidase, 5-nucleotidase), tubulovesicles (H+/K(+)-ATPase) and rough endoplasmic reticulum (NADPH-cytochrome-c-reductase) were mainly found in P3, which also contained the majority of 3H-PG E2 binding sites. In contrast, prostanoid binding was barely detectable in S1. Density fractionation of P3 revealed that 3H-PG E2 binding sites shared a similar sedimentation profile with plasma membranes and tubulovesicular markers. No or negative correlation was found with lysosomes, rough endoplasmic reticulum and mitochondria. We conclude that mucosal PG E2 receptors are predominantly located at the cell surface. This supports the view that prostanoids inhibit gastric secretion through membrane receptors, but gives no clue for intracellular "protective" working points.
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PMID:Subcellular localization of prostaglandin E2 receptors in the gastric mucosa. 134 83

Hepatic microsomal activities of acyl-CoA:cholesterol acyltransferase (ACAT) and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, rate-limiting enzymes in cholesterol esterification and cholesterol synthesis, and the concentration sand compartmentalization of esterified and unesterified cholesterol, were studied in carp acclimated to 10 and 30 degrees C. Irrespective of acclimation temperature, carp-liver ACAT is characterized by an apparent Km-value for oleoyl-CoA of 11-15 microM and displays an optimum activity at pH 7.4. The enzyme activity is reduced approx. 2-fold upon preincubation of microsomes with alkaline phosphatase. Arrhenius plots of ACAT-activity are curvilinear, with curvatures considerably affected by the acclimation temperature of the fish. Carp HMG-CoA reductase has been characterized previously by Teichert and Wodtke ((1987) Biochim. Biophys. Acta 920, 161-170). When measured at 30 degrees C, ACAT activities from 30 degrees C- and 10 degrees C-acclimated carp are identical (approx. 6 pmol/min per mg protein), whilst 'expressed' HMG-CoA reductase activity (18.1 +/- 12.2 pmol/min per mg protein for 30 degrees C-acclimated carp vs. 159.8 +/- 106.6 pmol/min per mg protein for 10 degrees C-acclimated carp) is enhanced 9-fold in the cold environment. This disparity indicates that cold-acclimation results in a massive increase in the capacity for hepatic cholesterol synthesis relative to hepatic cholesterol esterification. At the same time, hepatic compositional analysis reveals identical contents of unesterified cholesterol in either groups of carp but significantly decreased (3-fold) amounts in cholesterol ester (and also in triacylglycerol, 4-fold) in cold-acclimated carp. Moreover, microsomal fractions display lower cholesterol to phospholipid ratios in the cold. In contrast, concentrations of either cholesterol fractions (and of triacylglycerols) in plasma--the mobile compartment for lipoprotein transport--do not differ in cold- and warm-acclimated carp. Based on current concepts of cholesterol metabolism, it is concluded that the cold-enhanced expression of hepatic HMG-CoA reductase activity is a homeostatic response directed against and compensating for a cold-induced but not yet characterized deficiency in hepatic cholesterol availability.
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PMID:Acyl-CoA: cholesterol acyltransferase and 3-hydroxy-3-methylglutaryl-CoA reductase in carp-liver microsomes: effect of cold acclimation on enzyme activities and on hepatic and plasma lipid composition. 145 Feb 16

We previously reported that dog diabetes results in hypercholesterolemia and the accumulation of a high-density lipoprotein (HDL) subclass, HDL1. Hypercholesterolemic diabetic rodents exhibit hyperphagia, intestinal hypertrophy, and increased intestinal cholesterol synthesis and absorption; intestinal 3-hydroxy-3-methylglutaryl (HMG) CoA reductase activity is increased, whereas hepatic activity is unchanged or reduced. To determine whether similar mechanisms operate in the hypercholesterolemic diabetic dog, we measured hepatic and intestinal cholesterologenesis. Streptozocin-alloxan-induced diabetic dogs allowed access to food ad libitum were hyperphagic and hypercholesterolemic (10.1 vs. 4.47 mM) but normotriglyceridemic. Plasma HDL1 concentrations were markedly increased. Differences in renal and hepatic function were not statistically significant, except serum alkaline phosphatase, which was elevated 4-fold (P = 0.0003). Urinary mevalonate, an index of whole-body cholesterol synthesis, was increased 6-fold. Intestinal and hepatic weights were both increased, and direct measurements showed crypt and villus thickening. The activity of HMG CoA reductase per gram organ weight was increased 1.7-fold in liver and 2.1-fold in intestine. Calculated whole-organ activity in intestine was nearly twice that in liver. These observations provide strong evidence that intestinal cholesterogenesis is involved in the pathogenesis of hypercholesterolemia in dog diabetes and support the conclusion that increased cholesterol synthesis plays a role in the hypercholesterolemia of diabetes.
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PMID:Intestinal and hepatic cholesterogenesis in hypercholesterolemic dyslipidemia of experimental diabetes in dogs. 175 3

The authors studied distribution of alkaline and acid phosphatases, non specific esterase and NADH2 tetrazolium reductase in the dental pulp of children treated by fix orthodontic appliances. All the enzymes studied exhibited positive reaction, the activity, however, was lower than in the controls, except of the alkaline phosphatase. The results of the study demonstrated that the forces between 60-200 g cannot be evaluated as biologically favorable.
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PMID:[Histochemical observations on enzyme activity of the dental pulp following the orthodontic therapy]. 181 66

Treatment of rat liver microsomes with alkaline phosphatase results in a loss in the FMN but not the FAD flavin prosthetic group of NADPH-cytochrome P-450 reductase (Taniguchi, H. and Pyerin, W. (1987) Biochim. Biophys. Acta 912, 295-307). Experiments were carried out to evaluate the effect of preventing electron transfer from the FADH2 to FMN component of the reductase, and subsequent mixed function oxidase activity, on reduction of ferric chelates, production of H2O2, and the generation of .OH-like species by microsomes. Treatment with alkaline phosphatase was confirmed to decrease NADPH-cytochrome c, but not NADPH-ferricyanide, reductase activity by microsomes and by purified NADPH cytochrome P-450 reductase. The oxidation of hydroxyl radical scavenging agents by microsomes and reductase was decreased by the alkaline phosphatase treatment in accordance with the decline in cytochrome c reductase activity. This decrease in hydroxyl radical production occurred in the presence of various ferric chelate catalysts. Rates of microsomal reduction of the ferric chelates were also inhibited after alkaline phosphatase treatment. Production of H2O2 was decreased in accordance to the fall in cytochrome c reductase activity and .OH production. Rates of H2O2 production appeared to be rate-limiting for the overall generation of .OH as the addition of an external H2O2-generating system stimulated .OH production as well as prevented the decline in .OH production caused by the alkaline phosphatase treatment. These results suggest that both the FAD and FMN flavin prosthetic groups of the reductase contribute towards the reduction of various ferric chelates. However, loss of the FMN component and activities dependent on electron transfer from this prosthetic group result in a decrease in H2O2 production, which appears to be responsible for the decline in the generation of .OH-like species by microsomes after treatment with alkaline phosphatase.
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PMID:Inhibition of the oxidation of hydroxyl radical scavenging agents after alkaline phosphatase treatment of rat liver microsomes. 190 77


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