• BMB Reports
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• v.28 no.6
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• pp.515-522
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• 1995

The effects of the thyroid hormone ($T_3$) on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity were evaluated in a baby hamster kidney cell line, C100. The cells cultured in MEM were supplemented with 10% thyroid hormone-depleted fetal bovine serum (THDS-MEM) and had a 82.5% lower level of HMG-CoA reductase activity than the cells grown in a medium supplemented with fetal bovine serum (FBS-MEM). When $T_3$ was supplemented to THDS-MEM, the reduction of the reductase activity was blocked in a dose-dependent manner. In the cells grown in THDS-MEM containing $T_3$ at a concentration of $10^{-6}$ M, the level of HMG-CoA reductase activity was 91.8% relative to the cells grown in FBS-MEM. These changes in HMG-CoA reductase activity seemed to be at least partly due to the changes of HMG-CoA reductase mRNA levels. The level of HMG-CoA reductase mRNA in cells incubated in THDS-MEM decreased to 76.2% relative to the cells grown in FBS-MEM, while the level of reductase mRNA in cells incubated in THDS-MEM containing $T_3$ at a concentration of $10^{-6}$ M increased to 243.4% relative to the cells grown in FBS-MEM. The increase of HMG-CoA reductase mRNA level after $T_3$ treatment may have been due to the increased stability of reductase mRNA, because the transcriptional rate of the reductase gene did not change significantly in the presence or absence of $T_3$. These results indicate that $T_3$ stabilizes HMG-CoA reductase mRNA at the posttranscriptional level and regulates HMG-CoA reductase activity in a dose-dependent manner.

• Journal of the Korean Society of Food Science and Nutrition
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• v.21 no.5
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• pp.580-593
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• 1992

Cholesterol have many essential functions as a component of cellular and subcellular membranes, metabolic precursor of bile acids and steroid hormones, and obligatory part of the metabolic systems involved in DNA synthesis and cell division. These essential funtions demand a continuous and appropriate supply of cholesterol to the tissues. Body cholesterol pool is maintained by the balance of acquirement from diets, de novo synthesis, and excretion either as bile acids or neutral steroids. In these metabolic process, cholesterol biosynthesis is controlled by the change in the activity of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase. Under most physiological or nutritional situations, the activity of this enzyme is adroitly regulated to maintain tissue cholesterol balance. Excess cholesterol accumulation in the cells induces the decrease in the number of LDL-receptor, followed by the increase in the level of serum LDL-cholesterol. Increase in the level of serum cholesterol appears to be an important determinant for the incidence of the coronary heart disease. Dietary intervention may be helpful in alleviating an increase in the level of serum cholesterol or body cholesterol pool.

• Asian-Australasian Journal of Animal Sciences
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• v.6 no.2
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• pp.281-290
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• 1993

This experiment was designed to evaluate the effect of degree of unsaturation (Experiment 1) and the chain length of constituent fatty acids of dietary fats (Experiment 2) on-3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activities in the liver and small intestine of chicks. Chicks were fed experimental diets for 10 days and then killed for the determination of the HMG-CoA reductase activities in the intestinal epithelial cell and hepatic microsomes. The hepatic HMG-CoA reductase activity showed the highest value in chicks fed the tallow-containing diet. Chicks fed diets containing safflower or coconut oil resulted in a significantly lower intestinal HMG-CoA reductase activity in comparison with those fed the olive oil-containing diet. The hepatic HMG-CoA reductase activity was significantly higher when fat-free and trilaurin were fed than when any other triglycerides were fed. This activity showed the lowest value in the chicks fed the diet containing tristearin. The HMG-CoA reductase activities in the jejunum and ileum were significantly or tended to be higher when trilaurin was fed than when any other triglycerides were fed. Except when trilaurin was fed, the presence of saturated fat in the diet did not have a significant effect on the intestinal HMG-CoA reductase activity, unlike the effect shown when a highly unsaturated fat was added to the diet. There was no significant correlation between the HMG-CoA reductase activities of the liver and intestinal, and the HMG-CoA reductase activity and cholesterol content of the intestinal epithelial cells.

• KSBB Journal
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• v.6 no.1
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• pp.55-61
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• 1991

The objective of this in vitro study is to screen a possible inhibitor, originated from some chinese herb medicines, of 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase that is the major regulatory enzyme of hepatic cholesterol biosynthesis. Fourteen kinds of herbal plant were extracted with water and evaporated for prescreening. The methanol extracts of the effective 3 kinds (9 species) were fractionated with chloroform, ethylacetate, butanol and water, and vacuum evaporated. The degree of inhibition of the extracts to HMG-CoA reductase activity was calculated by the spectrophotometric method using microsomal protein of Saccharomyces cerevisiae ATCC 42949 as an enzyme source. Among these samples, marked inhibitory effects were observed in the extracts of ethylacetate and chloroform fractions of the Rosa rugosa roots, and those of butanol, ehtylacetate and water fractions of pine leaves. Also, the inhibitory effects of the extracts obtained from buckwheat shell and the roots of Rosaceae were found.

• Korean Journal of Poultry Science
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• v.23 no.3
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• pp.129-134
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• 1996

his study was conducted to determine the effect of dietary garlic supplementation on the growing performance and activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in broiler chicks from 3 to 5 wk post hatching. Fifty chicks were divided into 5 groups with 10 replicates per treatment and placed in a wire battery cage. Five levels of dietary garlic(0, 0.1, 0.3, 0.6 and 1.0%) were provided in an one way analysis. Feed and water were given ad libitum. Feed intake, weight gain and feed conversion rate(FCR) were not affected by the garlic supplementations. The HMG-CoA reductase activity decreased significantly(P<0.05) with the supplementation of garlic powder, compared to the garlic free group. As the dietary garlic level was increased, chicks showed decreased lipid contents in liver and blood serum. The results of this study indicate that blood cholesterol of chicks fed garlic supplemented diet might be reduced by inhibition of RMG-CoA reductase activity.

• Journal of Life Science
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• v.18 no.4
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• pp.427-434
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• 2008

Osteonecrosis of the femoral head (ONFH) is a multifactorial disease and certain individuals are more at risk or may be predisposed to it. An altered lipid metabolism is one of the major risk factors for osteonecrosis, especially corticosteroid therapy and alcoholism. 3-hydroxy-3-methylglutaryl coenzyme A. (HMG-CoA) reductase inhibitors, stalin used as lipid-clearing agent, have been known to decrease the risk of osteonecrosis in patients receiving steroids and affect coagulation and fibrinolysis. Therefore we evaluated the association of HMG-CoA reductase gene polymorphisms and haplotypes between osteonecrosis patients and normal controls. We directly sequenced the HMG-CoA reductase gene in 24 Korean individuals, and identified five sequence variants. Four SNPs (-6933C>T, -6045T>G, +12673G>A, and +18128C>T) were selected and genotyped in 349 male ONFH patients and 300 male control subjects. The genotypes, allele frequencies, and haplotypes of the polymorphisms in the total patients as well as in the subgroup by etiology were not significantly different from those in the control group. In addition, no significant differences between each genotype of the polymorphisms and plasma lipid level could be found in the control group. These results suggest that the polymorphisms and haplotypes of HMG-CoA reductase gene are unlikely to be associated with a susceptibility to ONFH.

• Food Engineering Progress
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• v.13 no.4
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• pp.243-250
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• 2009

Pravastatin sodium, competitive inhibitors of HMG-CoA(3-hydroxy-3-methylglutaryl coenzyme A) reductase, is produced from the culture broth of Streptomyces carbophilus KCCM 10370, The production of Pravastatin sodium was increased about 45 fold compared to wild type by UV mutation. Production of Pravastatin was also improved by continuous feeding of Compactin sodium to 24% and bioconversion ratio was also increased to 4.3% by intermittent addition. In main culture, concentration of Compactin sodium was kept less than 0.1%(w/v) under continuous feeding of Compactin sodium then product was 0.49% and bioconversion was 70%. After finishing the fermentation, Pravastatin was purified by various chromatographies such as Diaion HP20 resin column, Partition, and ODS(Octa-Decylsilyl Silicagel) resin column with a final yield of 70~72% and over 99.7% purity. The IR, UV, and NMR study of the purified Pravastatin sodium showed the same pattern as that of EP(European Pharmacopoeia).

• Journal of Applied Biological Chemistry
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• v.61 no.1
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• pp.1-8
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• 2018

The objective of this study was to compare the antihyperlipidemic effects of different Dendropanax morbifera leaf extracts in vitro. The extracts differed in terms of specimen age, harvesting season, and extraction method. RAW 264.7 cells were pretreated with these extracts and stimulated by oxidized low-density lipoprotein. Ethanol was used to induce toxicity in HepG2 cells. Cellular lipid accumulation was quantified using oil red O staining in both these cells. The extracts were evaluated for their inhibitory effects on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. RAW 264.7 cells treated with the 60% ethanol extract of an 8-year-old specimen harvested in November exhibited the lowest lipid accumulation. The 30% ethanol extract of a 5-year-old specimen harvested in May exhibited the greatest protection from ethanol-induced cytotoxicity in HepG2 cells. The hot water extract of an 8-year-old specimen harvested in May showed the greatest inhibition of HMG-CoA reductase. These results showed that D. morbifera extracts prepared from leaves that are harvested in May possess the highest antihyperlipidemic effects.

• Journal of the Korean Society of Food Science and Nutrition
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• v.12 no.3
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• pp.212-218
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• 1983

The effect of dietary calcium and magnesium on the 3-Hydroxy-3-methyl-glutaryl coenzyme A reductase (E.C. 1.1.1.34) in rabbit's liver microsomal protein was studied for a period of 4 weeks using isocalories and isonitro-genous as a basal diet. The experimental rabbits fed the following basal diets, such as crude protein 68.45%, carbohydrates 13.38%, fats 16.17% and added some sorts of calcium and magnesium, according to experimental plan making. The subject rabbits were divided into 9 feeding groups. The results are summarized as follows. Body weight gains per week of the groups fed magnesium and basal diet showed a little bit increase, but the groups fed calcium and basal diet showed a little bit decrease compare with control group. In case of serum magnesium, control group was 9.5mg% groups fed basal diet and magnesium were 8.27mg% in average, groups fed basal diet and calcium were 4.45mg% in average. In case of serum calcium, control group was 15.3mg%, groups fed basal diet and magnesium were 14.6mg% in average, groups fed basal diet and calcium were 14.1mg% in average. There was no great difference between magnesium fed groups in serum calcium. In serum triglyceride, control group was 82.8mg%, groups fed magnesium and basal diet were 60.3mg% in average, groups fed calcium and basal diet were 69.5mg% in average. The calcium fed groups were higher than the magnesium fed groups in serum triglyceride. In serum cholesterol, control group was 80mg%, groups fed magnesium and basal diet were 64.3mg% in average, groups fed calcium and basal diet were 56.3mg% in average. The calcium fed groups were lower than the magnesium fed groups in serum cholesterol. In case of the 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity, control group was 0.998nmol/min/mg protein, groups fed magnesium and basal diet of HMG-CoA were 0.849nmol/min/mg in average.

• Applied Biological Chemistry
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• v.41 no.1
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• pp.47-52
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• 1998

3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR) catalyzes the conversion of HMG-CoA to mevalonic acid, the first intermediate of isoprenoid biosynthetic pathway in plants. The enzyme was solubilized with 0.4% Brij (polyoxyethylene ether) W-1 from a microsomal fraction of etiolated rice seedlings (Oryza sativa L.) in which its maximal activity was observed on the fourth day after germination. HMGR was purified to near homogeneity by employing $(NH_4)_2SO_4$ fractionation plus chromatographic procedures including DEAE-Sephadex A-50 and HMG-CoA-hexane-agarose affinity column. The size of the purified enzyme was estimated to be 55 kDa when judged by SDS-PAGE analysis with silver staining method. The apparent $K_m$ and $V_{max}$ values for HMG-CoA were determined to be $180\;{\mu}M$ and 107 pmol/min/mg, and those for NADPH were $810\;{\mu}M$ and 32.1 pmol/min/mg, respectively.