Cholesterol synthesis is a complex, multi-step pathway that has many layers of regulation to ensure homeostasis. As an important rate-limiting enzyme, the regulation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the best understood [1,2]. HMGCR is the well-known target of the statin...
A simplified cholesterol synthesis pathway. The basic initial molecule is acetyl CoA, which is subsequently enzymatically processed into intermediate compounds hydroxymethylglutaryl-CoA (HMG CoA), mevalonic acid, squalene and lanosterol. The pathway for synthesis then diverges into two pathways that make ...
98]. Specifically, elevated cholesterol synthesis gene expression was found prevalent in breast cancer stem-cell tumorspheres and inhibition of the cholesterol synthesis pathway by statin hindered the sphere formation in vitro [99]. On the other hand, atorvastatin...
a key enzyme in cholesterol synthesis. Since cholesterol levels in cells are tightly controlled (cholesterol is critical to many cellular functions), the shutdown of cellular cholesterol synthesis causes the cell to respond by increasing the activity of the LDL receptor on the cell surface, which ...
form lanosterol and subsequently to synthesize cholesterol. The process is regulated by a negative feedback mechanism with the downstream products.52,53The SREBP pathway and the HMGCR degradation pathway serve as two major negative feedback regulatory mechanisms to regulate cholesterol de novo synthesis...
Cholesterol biosynthesis is a highly regulated, oxygen-dependent pathway, vital for cell membrane integrity and growth. In fungi, the dependency on oxygen for sterol production has resulted in a shared transcriptional response, resembling prolyl hydroxyl
Hepatic bile acid synthesisCholesterol delivered to the liver via HDL enters the bile acid synthesis pathway (also known as the cholesterol catabolic pathway), which begins with the enzymatic modulation of hepatic cholesterol to 7-α-hydroxycholesterol by cholesterol 7-α-hydroxylase (CYP7A1) (80)....
DHCR7 catalyzes the conversion of 7-dehydrocholesterol to cholesterol, which is the final step of cholesterol synthesis in the Kandutsch–Russell pathway. [9] Previous research has indicated that DHCR7 plays important roles in several kinds of malignant tumors. For example, elevated DHCR7 ...
Cholesterol de novo synthesis is a highly regulated, multistep process known as the mevalonate pathway. Primary place of cholesterol production is the liver, which contributes 20–25% of total cholesterol synthesis, while cholesterol is also synthesized in the intestines, adrenal glands, and ...
in thereverse cholesterol transportpathway. This pathway serves to remove cholesterol from peripheral cells into HDL, and to transport cholesterol, in the form of cholesterol esters, to the liver or to steroidogenic tissues for excretion or utilization in bile salt orsteroid hormone synthe...