Quantification of urinary mevalonic acid as a biomarker of HMG-CoA reductase activity by a novel translational LC–MS/MS method

Bioanalysis ◽  
2014 ◽  
Vol 6 (7) ◽  
pp. 919-933 ◽  
Author(s):  
Alison VM Rodrigues ◽  
James L Maggs ◽  
Stephen J McWilliam ◽  
Munir Pirmohamed ◽  
Muireann Coen ◽  
...  
Keyword(s):  
Reductase Activity ◽  
Mevalonic Acid ◽  
Hmg Coa Reductase ◽  
Coa Reductase

scholarly journals Regulation of hepatic cholesterol biosynthesis. Effects of a cytochrome P-450 inhibitor on the formation and metabolism of oxygenated sterol products of lanosterol

1989 ◽  
Vol 264 (2) ◽  
pp. 495-502 ◽  
Author(s):  
J Iglesias ◽  
G F Gibbons
Keyword(s):  
Reductase Activity ◽  
Cholesterol Biosynthesis ◽  
Mevalonic Acid ◽  
Subcellular Fractions ◽  
Hmg Coa Reductase ◽  
Hepatocyte Cultures ◽  
C 32 ◽  
Lanosterol Demethylase ◽  
Cholesterol Precursor ◽  
Coa Reductase

The involvement of oxygenated cholesterol precursors in the regulation of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was studied by examining the effect of ketoconazole on the metabolism of mevalonic acid, lanosterol and the lanosterol metabolites, lanost-8-ene-3 beta,32-diol,3 beta-hydroxylanost-8-en-32-al and 4,4-dimethylcholesta-8,14-dien-3 beta-ol, in liver subcellular fractions and hepatocyte cultures. Inhibition of cholesterol synthesis from mevalonate by ketoconazole at concentrations up to 30 microM was due exclusively to a suppression of cytochrome P-450LDM (LDM = lanosterol demethylase) activity, resulting in a decreased rate of lanosterol 14 alpha-demethylation. No enzyme after the 14 alpha-demethylase step was affected. When [14C]mevalonate was the cholesterol precursor, inhibition of cytochrome P450LDM was accompanied by the accumulation of several labelled oxygenated sterols, quantitatively the most important of which was the C-32 aldehyde derivative of lanosterol. There was no accumulation of the 24,25-oxide derivative of lanosterol, nor of the C-32 alcohol. Under these conditions the activity of HMG-CoA reductase declined. The C-32 aldehyde accumulated to a far greater extent when lanost-8-ene-3 beta,32-diol rather than mevalonate was used as the cholesterol precursor in the presence of ketoconazole. With both precursors, this accumulation was reversed at higher concentrations of ketoconazole in liver subcellular fractions. A similar reversal was not observed in hepatocyte cultures.

A Novel NAD+/MWNTs Nanocomposite-Based Electrochemical Biosensor for Measuring Mevalonic Acid

2014 ◽  
Vol 605 ◽  
pp. 388-391 ◽  
Author(s):  
Rungtiva Palangsuntikul ◽  
Saithip Pakapongpan ◽  
Porntip Khownarumit ◽  
Werasak Surareungchai
Keyword(s):  
Electrocatalytic Activity ◽  
Electrochemical Biosensor ◽  
Limit Of Detection ◽  
Reductase Activity ◽  
Mevalonic Acid ◽  
Fast Response ◽  
Good Stability ◽  
Screen Printed Electrode ◽  
Hmg Coa Reductase ◽  
Coa Reductase

A novel, simple and precise electrochemical biosensor, was developed for measuring mevalonic acid (MA) concentration, which is thought to be a good indicator of HMG-CoA reductase activity. This sensor is based on noncovalent-linking NAD+/MWNTs nanocomposite coated on a screen-printed electrode (SPE). The resulting biosensor exhibited excellent electrocatalytic activity, fast response and good stability to MA. At the NAD+/MWNTs-modified SPE, the current is linear with the concentration of MA being within a concentration range from 18.1 to 145 μM with a limit of detection down to 4.25 μM (S/N = 3), and the sensor exhibited a sensitivity of 92.2 μA/mM.

The effects of tunicamycin, mevinolin and mevalonic acid on HMG-CoA reductase activity and nuclear division in the myxomycete Physarum polycephalum

1989 ◽  
Vol 92 (3) ◽  
pp. 341-344
Author(s):  
W. Engstrom ◽  
O. Larsson ◽  
W. Sachsenmaier
Keyword(s):  
Physarum Polycephalum ◽  
Nuclear Division ◽  
Reductase Activity ◽  
Mevalonic Acid ◽  
Minor Effect ◽  
Hmg Coa Reductase ◽  
Rate Limiting Step ◽  
Coa Reductase ◽  
A Minor ◽  
Rate Limiting

The effects of two inhibitors of 3-hydroxy 3-methyl glutaryl-coenzyme A reductase (tunicamycin and mevinolin) on nuclear division in the myxomycete Physarum polycephalum were examined. Tunicamycin exerted a minor effect on division in synchronized cultures, whereas mevinolin delayed the second, third and fourth nuclear divisions with increasing efficiency. Mevinolin also appeared to be the more potent inhibitor of HMG-CoA reductase, which catalyses the rate-limiting step in the biosynthesis of cholesterol and other isoprene derivatives. These effects of mevinolin could be partially reversed by the addition of mevalonate, suggesting that mevinolin exerts its inhibitory effects on Physarum nuclear division by decreasing the activity of HMG-CoA reductase.

scholarly journals The absolute rate of cholesterol biosynthesis in monocyte-macrophages from normal and familial hypercholesterolaemic subjects

1984 ◽  
Vol 219 (2) ◽  
pp. 461-470 ◽  
Author(s):  
D D Patel ◽  
C R Pullinger ◽  
B L Knight
Keyword(s):  
Cholesterol Synthesis ◽  
Reductase Activity ◽  
Cholesterol Biosynthesis ◽  
Specific Radioactivity ◽  
Density Lipoprotein ◽  
Cellular Protein ◽  
True Rate ◽  
Hmg Coa Reductase ◽  
Coa Reductase ◽  
In Cells

The true rate of cholesterogenesis in cultured monocyte-macrophages was determined from the incorporation of [2-14C]acetate into cholesterol, using the desmosterol (cholesta-5,24-dien-3 beta-ol) that accumulated in the presence of the drug triparanol to estimate the specific radioactivity of the newly formed sterols. It was shown that this procedure could be successfully adapted for use with cultured monocytes despite the accumulation of other unidentified biosynthetic intermediates. In cells maintained in 20% (v/v) whole serum approx. 25% of the sterol carbon was derived from exogenous acetate. Cholesterol synthesis was as high in normal cells as in cells from homozygous familial hypercholesterolaemic (FH) subjects and accounted for 50% of the increase in cellular cholesterol. The addition of extra low-density lipoprotein (LDL) reduced cholesterol synthesis, apparently through a decrease in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). When incubated in lipoprotein-deficient serum some cells did not survive, but those that remained showed a normal increase in protein content; the amount of cellular protein and cholesterol in each well did not increase and cholesterol synthesis was reduced by over 80%. HMG-CoA reductase activity fell less dramatically and the proportion of sterol carbon derived from exogenous acetate increased, suggesting that the low rate of cholesterogenesis with lipoprotein-deficient serum was due to a shortage of substrate. The results indicate that under normal conditions monocyte-macrophages obtain cholesterol from endogenous synthesis rather than through receptor-mediated uptake of LDL, and that synthesis together with non-saturable uptake of LDL provides the majority of the cholesterol required to support growth.

scholarly journals The roles of different protein kinases and of calmodulin in the effects of Ca2+ mobilization on 3-hydroxy-3-methylglutaryl-CoA reductase activity in isolated rat hepatocytes

1991 ◽  
Vol 273 (2) ◽  
pp. 485-488 ◽  
Author(s):  
V A Zammit ◽  
A M Caldwell
Keyword(s):  
Protein Kinase ◽  
Reductase Activity ◽  
Rat Hepatocytes ◽  
Total Activity ◽  
Isolated Hepatocytes ◽  
Isolated Rat Hepatocytes ◽  
Hmg Coa Reductase ◽  
Lysosomal Proteolysis ◽  
Dependent Protein ◽  
Coa Reductase

The roles of protein kinase C, Ca2+/calmodulin-dependent protein kinase and AMP-activated protein kinase in the phosphorylation of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase induced by Ca2(+)-mobilizing conditions in isolated hepatocytes were investigated. Only partial evidence for the involvement of AMP-activated kinase was found. Antagonism of calmodulin action prolonged the decrease in expressed/total activity ratio induced by vasopressin plus glucagon. Protease inhibitors active against Ca2(+)-dependent cytosolic proteases or lysosomal proteolysis did not attenuate the loss of total HMG-CoA reductase induced by glucagon plus vasopressin, but calmodulin antagonists largely prevented this effect.

Differential effects of dietary fat on chick plasma and liver composition and HMG-CoA reductase activity

1999 ◽  
Vol 10 (4) ◽  
pp. 198-204 ◽  
Author(s):  
Mercedes Castillo ◽  
José H Hortal ◽  
Almudena Gil-Villarino ◽  
Purificación Luque ◽  
José Iglesias ◽  
...  
Keyword(s):  
Dietary Fat ◽  
Reductase Activity ◽  
Hmg Coa Reductase ◽  
Differential Effects ◽  
Coa Reductase

scholarly journals Effect of portacaval anastomosis on hepatic HMG-CoA-reductase activity in normal rats

FEBS Letters ◽  
1977 ◽  
Vol 75 (1-2) ◽  
pp. 101-104 ◽  
Author(s):  
G.H. Bützow ◽  
F.W. Ossenberg ◽  
K. Becker ◽  
Chr. Schudt ◽  
U. Gaertner
Keyword(s):  
Reductase Activity ◽  
Portacaval Anastomosis ◽  
Hmg Coa Reductase ◽  
Coa Reductase
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