Title: Cholesterol Synthesis - an overview | ScienceDirect Topics
Headings: Cholesterol Synthesis
Cholesterol Synthesis
Cholesterol Synthesis
7 Regulation of Cholesterol Synthesis
7.1 Transcription
7.2 Posttranslational Regulation
7.3 Other Modes of Regulation
Cholesterol Synthesis
Abstract
Molecular Cell Biology
Cholesterol Biosynthesis
CHOLESTEROL | Sources, Absorption, Function and Metabolism
Biosynthesis
Tissue Cholesterol Synthesis
Regulation of Synthesis
Diabetes Mellitus and Intestinal Niemann-Pick C1–Like 1 Gene Expression
1.1 Cholesterol Synthesis
Cholesterol: Sources, Absorption, Function, and Metabolism
Tissue Cholesterol Synthesis
Volume 1
Cholesterol Biosynthesis and Congenital Defects
Dyslipidemia
Pantethine
Dosage
Precautions
Vitamin D Hormone
2 A View from Evolution

Content: First, sterols signal for the enzymes to be ubiquitylated by an E3 ligase. In this process, the 76-amino acid protein ubiquitin is attached to the target protein, which is subsequently poly-ubiquitylated, marking it for degradation by the proteasome. In the case of SM, the E3 ligase is MARCH6, but for HMGCR, several E3 ligases have been proposed, including gp78, TRC8, HRD1 and also MARCH6. An intriguing difference between sterol-stimulated degradation of HMGCR and SM is that degradation of the former is stimulated by oxysterols and metabolic intermediates of the mevalonate pathway, whereas SM degradation is accelerated by cholesterol. This may allow differential production of cholesterol and nonsterol products, since HMGCR acts prior to the isoprenoid (nonsterol) branch point, whereas SM acts at a later stage from which mostly sterols (including cholesterol) are formed. In contrast to SM and HMGCR, the final enzyme in the Bloch pathway, DHCR24, is remarkably stable under changing sterol conditions, although its activity is affected by other posttranslational mechanisms as described in the following section (Luu et al., 2014 ). 7.2.2 Phosphorylation
The addition of a phosphate group to serine, threonine or tyrosine can have significant effects on enzyme activity. While it is known from large-scale mass spectrometry studies that many cholesterol synthesis enzymes are phosphorylated, very little has been done to determine the functional consequences of this modification. Only three enzymes have more detailed information.