The Role of Structure and Biophysical Properties in the Pleiotropic Effects of Statins

Autor: Christopher Murphy, Evelyne Deplazes, Alvaro Garcia, Charles G. Cranfield
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Models
Molecular
Lipid Bilayers
Review
Bioinformatics
030226 pharmacology & pharmacy
Protein Structure
Secondary
lcsh:Chemistry
0302 clinical medicine
lcsh:QH301-705.5
Spectroscopy
Biotransformation
Lipoprotein cholesterol
hepatoselectivity
Anticholesteremic Agents
General Medicine
Computer Science Applications
Liver
membranes
Thermodynamics
lipids (amino acids
peptides
and proteins)
Competitive inhibitor
Hydrophobic and Hydrophilic Interactions
Protein Binding
Statin
medicine.drug_class
Hypercholesterolemia
pleiotropic effects
Catalysis
statins
Inorganic Chemistry
03 medical and health sciences
medicine
Humans
cardiovascular diseases
Physical and Theoretical Chemistry
Prescribed medications
drug-membrane interactions
Molecular Biology
Serum cholesterol
business.industry
Organic Chemistry
Cell Membrane
nutritional and metabolic diseases
Biological Transport
Cholesterol
LDL
030104 developmental biology
Pleiotropy (drugs)
lcsh:Biology (General)
lcsh:QD1-999
Hepatocytes
Hydroxymethylglutaryl CoA Reductases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
business
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 21, Iss 8745, p 8745 (2020)
ISSN: 1422-0067
Popis: Statins are a class of drugs used to lower low-density lipoprotein cholesterol and are amongst the most prescribed medications worldwide. Most statins work as a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR), but statin intolerance from pleiotropic effects have been proposed to arise from non-specific binding due to poor enzyme-ligand sensitivity. Yet, research into the physicochemical properties of statins, and their interactions with off-target sites, has not progressed much over the past few decades. Here, we present a concise perspective on the role of statins in lowering serum cholesterol levels, and how their reported interactions with phospholipid membranes offer a crucial insight into the mechanism of some of the more commonly observed pleiotropic effects of statin administration. Lipophilicity, which governs hepatoselectivity, is directly related to the molecular structure of statins, which dictates interaction with and transport through membranes. The structure of statins is therefore a clinically important consideration in the treatment of hypercholesterolaemia. This review integrates the recent biophysical studies of statins with the literature on the physiological effects and provides new insights into the mechanistic cause of statin pleiotropy, and prospective means of understanding the cholesterol-independent effects of statins.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje