Cholesterol Biosynthesis: A Mechanistic Overview

Abstract

Cholesterol is an essential component of cell membranes and the precursor for the synthesis of steroid hormones and bile acids. The synthesis of this molecule occurs partially in a membranous world (especially the last steps), where the enzymes, substrates, and products involved tend to be extremely hydrophobic. The importance of cholesterol has increased in the past half-century because of its association with cardiovascular diseases, which are considered one of the leading causes of death worldwide. In light of the current need for new drugs capable of controlling the levels of cholesterol in the bloodstream, it is important to understand how cholesterol is synthesized in the organism and identify the main enzymes involved in this process. Taking this into account, this review presents a detailed description of several enzymes involved in the biosynthesis of cholesterol. In this regard, the structure and catalytic mechanism of the enzymes involved in cholesterol biosynthesis, from the initial two-carbon acetyl-CoA building block, will be reviewed and their current pharmacological importance discussed. We believe that this review may contribute to a deeper level of understanding of cholesterol metabolism and that it will serve as a useful resource for future studies of the cholesterol biosynthesis pathway.

The effect of commercially available chicken feed and chicken meat on body weight and serum estrogen levels in female albino Wistar rats

“…This could be attributed to amplified cholesterol levels in the body after such consumption facilitating steroidal hormones synthesis (Cinar et al, 2012). Augmented cholesterol levels enable body to produce more estrogens and other steroidal hormone as reported earlier (Cerqueira et al, 2016). Therefore, increased cholesterol and fat intake results in more cholesterol formation and storage in the body as adipose tissue ensuing increased growth and steroidal hormone E2 synthesis (Psifidi et al, 2016).…”

Serum lipid profile as a predictor of dengue severity: A systematic review and meta‐analysis

“…Liver damage is a hallmark of DF, particularly severe cases, and higher levels of liver enzymes (eg, aspartate aminotransferase, alanine aminotransferase) are frequent in dengue patients, having been reported in more than 80% of cases . Because the liver is a major site of cholesterol synthesis in humans, this suggests that the lesions induced by viral replication reduce the production of this lipid, resulting in the lower circulating levels of cholesterol observed in clinical studies …”

Fat for fuel: lipid metabolism in haematopoiesis

“…Cholesterol is produced de novo from acetyl‐CoA incorporation into the mevalonate pathway. The downstream metabolite of the mevalonate pathway, squalene, can be utilised by the Kandutsch–Russell and Bloch pathways to produce cholesterol …”

“…The downstream metabolite of the mevalonate pathway, squalene, can be utilised by the Kandutsch-Russell and Bloch pathways to produce cholesterol. 51 Haematopoietic stem and progenitor cell mobilisation has been observed under hypercholesterolaemic conditions such as atherosclerosis where increased myelopoiesis occurs in the BM and in secondary sites like the spleen to produce monocytes and neutrophils that infiltrate the plaque due to defects in cholesterol efflux 52 (Figure 3ci). This myeloproliferative phenotype has been mechanistically demonstrated by our laboratory and others to be a consequence of membrane cholesterol accumulation and subsequent lipid raft formation where the common b subunit of the IL-3/GM-CSF receptor or CD131 becomes more highly expressed.…”