Squalene undergoes a two-step cyclization to yield lanosterol catalyzed by sequalene mono-oxygenase and sequalene 2, 3 epoxidase enzymes. Sequalene mono oxygenase is the second committed step in cholesterol biosynthesis and lead to the formation squalene 2, 3 epoxide. This enzymatic reaction require supernatant protein factor (SPF) and NADPH as a cofactor to introduce molecular oxygen as an epoxide at the 2, 3 position of squalene. The activity of supernatant protein factor itself is regulated by phosphorylation/dephosphorylation (Singh et al., 2003). Through a series of 19 additiona lreactions, lanosterol is converted to cholesterol. The first sterol intermediate, lanosterol, is formed by the condensation of the 30 carbon isoprenoid squalene, and subsequent enzymatic reactions define the ‘post-squalene’ half of the pathway. The conversion of lanosterol to cholesterol involves the reduction of the C-24 double bond, removal of three methyl groups at the C-14 and C-4 positions, and ‘migration’ of the C-8(9) double bond (Herman, 2003). Some of the enzymatic reactions must occur …show more content…
As the VLDL circulate, their component triacylglycerols and most types of their apolipoproteins are removed in the capillaries of muscle and adipose tissues, sequentially converting the VLDL to intermediate density lipoproteins (IDL) and then to low-density lipoproteins (LDL). Peripheral tissues normally obtain most of their exogenous cholesterol from LDL by receptor mediated endocytosis. Inside the cell, cholesteryl esters are hydrolyzed by a lysosomal lipase to free cholesterol, which is either incorporated into cell membranes or reesterified by ACAT for storage as cholesteryl ester