Preferred Label : Lipid Synthesis Pathway;
NCIt related terms : SREBP control of lipid synthesis;
Alternative definition : BIOCARTA: Sterol-regulatory element binding proteins (SREBPs) play a key role in transcriptional
regulation of cholesterol metabolism in response to cholesterol levels in the cell.
When cholesterol is abundant in the cell, the SREBPs are retained in the ER. When
cholesterol levels decrease, SREBPs are cleaved and released to act as transcription
factors, binding to the promoters of genes such as the LDL receptor and HMG CoA Synthase.
Binding of SREBPs to the LDL receptor promoter increases the expression of LDL receptor
on the cell surface and increases the internalization of LDL from plasma, increasing
cellular cholesterol levels and lowering LDL cholesterol in the plasma. Upregulation
of genes such as HMG CoA synthase increases the biosynthesis of cholesterol. The SREBP
proteins are cleaved and activated by two proteases, S1P (Site 1 protease) and S2P
(Site 2 protease). S1P cleaves SREBP region in the ER lumen and S2P cleaves in the
transmembrane region of SREBPs. Regulation by sterols is provided by SCAP. SCAP activates
S1P when sterols are low, inducing SREBP activation, and does not activate S1P when
sterol levels increase. Drugs acting at various steps in this process can alter cholesterol
metabolism and plasma cholesterol levels that contribute to coronary heart disease.
The statins such as lovastatin are drugs that inhibit cholesterol biosynthesis, lowering
intracellular cholesterol levels and activating SREBP cleavage to increase LDLR expression
on the cell surface. Inhibition of S1P may provide another mechanism to alter plasma
cholesterol levels, as suggested by the low cholesterol levels in mice lacking the
S1P gene. Ligands that bind to SCAP also lower cholesterol levels through induction
of LDLR expression. (This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_s1pPathway;
Origin ID : C39226;
UMLS CUI : C1517899;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
