scholarly journals A relationship between the activities of hepatic lanosterol 14α-demethylase and 3-hydroxy-3-methylglutaryl-CoA reductase

1988 ◽  
Vol 250 (1) ◽  
pp. 33-39 ◽  
Author(s):  
C Marco de la Calle ◽  
W Hwang ◽  
C R Pullinger ◽  
G F Gibbons
Keyword(s):  
Lipid Synthesis ◽  
Relative Increase ◽  
Rapid Decline ◽  
Intragastric Administration ◽  
Similar Time ◽  
Hmg Coa Reductase ◽  
Pre Treatment ◽  
Coa Reductase ◽  
Cytochrome P 450

At 1-2 h after intragastric administration of ketoconazole, a cytochrome P-450 inhibitor, to rats, there was a 50-60% decrease in the activity of hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. Inhibition reached a maximum at 6-12 h after the drug was given, but after 24 h enzyme activity was stimulated by 60%. The rates of synthesis of hepatic non-saponifiable lipids in vivo showed a similar time-dependent pattern of change. During the first few hours after drug administration, the hepatic cytochrome P-450-dependent metabolism of lanosterol was suppressed in vivo. However, 24 h after treatment, this activity was stimulated, an effect which was also observed by pre-treatment of the rats with the drug for several days. Suppression of hepatic HMG-CoA reductase and lanosterol 14 alpha-demethylase activities was accompanied by a relative increase in the accumulation of labelled polar sterols in the liver in vivo. In the intestine, ketoconazole also resulted in a rapid decline in the rate of synthesis of non-saponifiable lipids and an inhibition of lanosterol 14 alpha-demethylation in vivo. However, in contrast with the liver, there was no stimulation of non-saponifiable lipid synthesis after 24 h.

scholarly journals Hepatic and intestinal formation of polar sterols in vivo in animals fed on a cholesterol-supplemented diet

1988 ◽  
Vol 252 (2) ◽  
pp. 395-399 ◽  
Author(s):  
C Marco de la Calle ◽  
G F Gibbons
Keyword(s):  
Reductase Activity ◽  
Lipid Fraction ◽  
Dietary Cholesterol ◽  
Lipid Synthesis ◽  
Inverse Correlation ◽  
Normal Diet ◽  
Hmg Coa Reductase ◽  
Coa Reductase ◽  
Strong Inverse Correlation

In rats fed on a diet containing 1% cholesterol for 24 h, the decrease in hepatic non-saponifiable lipid synthesis, cholesterogenesis and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was accompanied by an increase in the proportion of newly synthesized polar sterols in vivo. In these animals there was also a strong inverse correlation between the proportion of polar sterols in the non-saponifiable lipid and hepatic HMG-CoA reductase activity. A similar correlation was not observed in animals fed on a normal diet. Cholesterogenesis in the intestine was not as sensitive to inhibition by dietary cholesterol as was that in the liver, and there was no increase in the polar-sterol content of the newly synthesized non-saponifiable-lipid fraction.

In Vivo LDL Receptor and HMG-CoA Reductase Regulation in Human Lymphocytes and Its Alterations During Aging

1995 ◽  
Vol 15 (7) ◽  
pp. 872-878 ◽  
Author(s):  
Thomas M. Stulnig ◽  
Helmut Klocker ◽  
H. James Harwood ◽  
Günther Jürgens ◽  
Dieter Schönitzer ◽  
...  
Keyword(s):  
Human Lymphocytes ◽  
Ldl Receptor ◽  
Hmg Coa Reductase ◽  
Coa Reductase

A 68-Year-Old Female with Progressive Pain and Weakness

2016 ◽  
Author(s):  
Jeffrey A. Cohen ◽  
Justin J. Mowchun ◽  
Victoria H. Lawson ◽  
Nathaniel M. Robbins
Keyword(s):  
Creatine Kinase ◽  
Muscle Biopsy ◽  
Creatine Kinase Level ◽  
Coenzyme A ◽  
Inflammatory Myopathy ◽  
Hmg Coa Reductase ◽  
System A ◽  
Coa Reductase ◽  
Cytochrome P 450

Statin myopathy can occur at anytime during use. This chapter discusses an approach to diagnosis, and emphasizes management considerations, including awareness of statin metabolism by the cytochrome P-450 system. A statin must be discontinued in any patient with evidence of myopathy or myalgias. A muscle biopsy should be done in cases that do not improve clinically or by creatine kinase level. It is important to note that there are cases of apparent statin myopathy which transform into a chronic autoimmune inflammatory myopathy. Antibodies to hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase have recently been identified in the majority of patients with autoimmune statin myopathy and this test may give further weight to treat with immunotherapy.

Bile duct cells: a novel in vitro model for the study of lipid metabolism and bile acid production

1999 ◽  
Vol 276 (2) ◽  
pp. G407-G414 ◽  
Author(s):  
Monika Zoltowska ◽  
Edgard E. Delvin ◽  
Khazal Paradis ◽  
Ernest Seidman ◽  
Emile Levy
Keyword(s):  
Bile Acid ◽  
Bile Duct ◽  
Bile Acids ◽  
Cytokeratin 19 ◽  
Sterol Metabolism ◽  
Hmg Coa Reductase ◽  
Biliary Epithelium ◽  
Duct Cells ◽  
Coa Reductase

Immortalized bile duct cells (BDC), derived from transgenic mice harboring the SV40 thermosensitive immortalizing mutant gene ts458, were utilized to investigate the role of the biliary epithelium in lipid and sterol metabolism. This cell model closely resembles the in vivo situation because it expresses the specific phenotypic marker cytokeratin 19 (CK-19), exhibits the formation of bile duct-like structures, and displays well-formed microvilli projected from the apical side to central lumen. The BDC were found to incorporate [14C]oleic acid (in nmol/mg protein) into triglycerides (121 ± 6), phospholipids (PL; 59 ± 3), and cholesteryl ester (16 ± 1). The medium lipid content represented 5.90 ± 0.16% ( P < 0.005) of the total intracellular production, indicating a limited lipid export capacity. Analysis of PL composition demonstrated the synthesis of all classes of polar lipids, with phosphatidylcholine and phosphatidylethanolamine accounting for 60 ± 1 and 24 ± 1%, respectively, of the total. Differences in PL distribution were apparent between cells and media. Substantial cholesterol synthesis was observed in BDC, as determined by the incorporation of [14C]acetate suggesting the presence of hydroxymethylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway. With the use of [14C]acetate and [14C]cholesterol as precursors, both tauro- and glycoconjugates of bile acids were synthesized, indicating the presence of cholesterol 7α- and 26R-hydroxylases, the key enzymes involved in bile acid formation. The transport of bile acids was not limited, as shown by their marked accumulation in the medium (>6-fold of cell content). HMG-CoA reductase (53.0 ± 6.7), cholesterol 7α-hydroxylase (15.5 ± 0.5), and acyl-CoA:cholesterol acyltransferase (ACAT; 201.7 ± 10.2) activities (in pmol ⋅ min−1 ⋅ mg protein−1) were present in the microsomal fractions. Our data show that biliary epithelial cells actively synthesize lipids and may directly contribute bile acids to the biliary fluid in vivo. This BDC line thus represents an efficient experimental tool to evaluate biliary epithelium sterol metabolism and to study biliary physiology.

scholarly journals An HMG-CoA Reductase Inhibitor, Cerivastatin, Suppresses Growth of Macrophages Expressing Matrix Metalloproteinases and Tissue Factor In Vivo and In Vitro

Circulation ◽  
2001 ◽  
Vol 103 (2) ◽  
pp. 276-283 ◽  
Author(s):  
Masanori Aikawa ◽  
Elena Rabkin ◽  
Seigo Sugiyama ◽  
Sami J. Voglic ◽  
Yoshihiro Fukumoto ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Tissue Factor ◽  
Reductase Inhibitor ◽  
Hmg Coa Reductase ◽  
Hmg Coa Reductase Inhibitor ◽  
Coa Reductase

scholarly journals Ameliorations in the Biomarker Indices of Dyslipidemia and Atherosclerotic Plaque by the Inhibition of HMG – CoA Reductase and Antioxidant Potential of Phytoconstituents of an Aqueous Seed Extract of Acacia Senegal (L.) Willd in Rabbits

2021 ◽  
Author(s):  
Jaykaran Charan ◽  
Priyanka Riyad ◽  
Heera Ram ◽  
Ashok Purohit ◽  
Sneha Ambwani ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
In Silico ◽  
Risk Index ◽  
Seed Extract ◽  
Atherogenic Index ◽  
Acacia Senegal ◽  
Hmg Coa Reductase ◽  
Coa Reductase

Abstract Background: The HMG-CoA inhibitor are used to control adverse cardiovascular event caused by Hypercholesterolemia and dyslipidaemia. The current study was aimed to evaluate the ability of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd to inhibit HMG-CoA reductase and regress the formation of atherosclerotic plaque. Methods: The chemical fingerprinting of the test extract was assessed by LC-MS. Consequently, the assessments of in-vitro, in-vivo, and in-silico were performed by following the standard methods.Results: The in-vitro assessment of the test extract revealed 74.1 % inhibition potential of HMG-CoA reductase. In-vivo evaluations of the test extract indicated that treated hypercholesterolemic rabbits exhibited a significant (𝑃 ≤ 0.001) ameliorations in the biomarker indices of the dyslipidaemia, such as the atherogenic index, Castelli risk index (I&II), atherogenic coefficient along with lipid profile. Concomitantly, significant reductions were observed in the atherosclerotic plaque area and antioxidants. The in-silico study of molecular docking shown interactions capabilities of key phytoconstituents of the test extract with target protein of HMG-CoA reductase which further validated by the molecular dynamics through potentail energy, NPT, NVT, RSMD and others. Subsequently, the ADMET analysis shown ideal druggability. Conclusion: The results indicate that phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd. could inhibit HMG-CoA reductase and improve the levels of antioxidants activity that may reduce symptoms associated with hypercholesterolemia.

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