ISSN: 2577-4360
Authors: Taylor M Borah, Alexandria C Guerra and Kevin Francis*
Global occurrence of cardiovascular diseases is a serious health concern resulting in over 2 million deaths annually. A major cause of cardiovascular disease is elevated levels of blood plasma cholesterol which leads to the precipitation of lipoproteins and arterial plaque formation. This review details treatment of hypercholesterolemia that target redox enzymes involved in the biosynthesis of the lipid. It begins with a brief discussion of both high- and low-density lipoproteins that are the vehicles for cholesterol transport in humans. An overview of the five stages of cholesterol anabolism in the liver is then provided focusing on the two rate-limiting redox enzymes involved in the pathway. These enzymes are 3-hydroxy-3-methylglutyl CoA reductase (HMGR) and squalene monooxygenase (SMO). The structure and catalytic mechanisms are presented in great detail to lay the foundation for a presentation of common cholesterol lowering drugs. The first of these are the statins that competitively inhibit HMGR and have shown the greatest success in both the treatment and prevention of cardiovascular diseases. An inhibitor of SMO called terbinafine is then discussed. This drug molecule is a fairly effective anti-fungal but is not currently approved in the U.S. to treat high cholesterol. However, it has been shown to lower low-density lipoproteins and exhibits promise to provide the framework for the development of new cholesterol lowering treatments to target SMO. It is hoped that this review article will raise awareness and spur future research into the treatment of hypercholesterolemia to treat and/or prevent cardiovascular disease.
Keywords: Cholesterol Biosynthesis; High and Low Density Lipoproteins; 3-Hydroxy-3-Methylglutyl Coa Reductase; Squalene Monooxygenase; Coenzyme A; Flavin Adenine Dinucleotide; Nucleotide Adenine Diphosphate; Statins; Terbinafine
