What is SREBP pathway?
The SREBPs (sterol regulatory element binding proteins) are membrane-bound transcription factors that control lipid synthesis in animal cells. The transcriptionally active amino terminus is released from the membrane following two sequential proteolytic steps that are carried out by S1P and S2P.
What does SREBP-2 do?
It has long been viewed that SREBP2 is primarily responsible for activation of genes involved in cholesterol synthesis, as opposed to fatty acid synthesis. In contrast, SREBP1c functions primarily in the liver to drive fatty acid synthesis, while SREBP1a can drive both pathways in all tissues.
How does SREBP control lipid and cholesterol biosynthesis?
In mammals, intracellular levels of cholesterol and fatty acids are controlled through a feedback regulatory system mediated by a family of transcription factors called sterol regulatory element-binding proteins (SREBPs). SREBPs are synthesized as inactive precursors bound to membranes of the endoplasmic reticulum.
What genes does SREBP regulate?
The target genes of SREBPs include the rate-limiting lipogenic and cholesterogenic genes, such as fatty acid synthase, HMG-CoA reductase and the LDL receptor[12,13]. Thus, SREBP activation promotes fatty acid and cholesterol biosynthesis, and cholesterol uptake.
How is SREBP regulated?
SREBP processing is mainly controlled by cellular sterol content. When sterol levels decrease, the precursor is cleaved to activate cholesterogenic genes and maintain cholesterol homeostasis.
What does HMG-CoA reductase do?
The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase catalyzes the conversion of HMG-CoA to mevalonate, a four-electron oxidoreduction that is the rate-limiting step in the synthesis of cholesterol and other isoprenoids.
Is SREBP a transcription factor?
Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate lipid homeostasis by controlling the expression of a range of enzymes required for endogenous cholesterol, fatty acid (FA), triacylglycerol and phospholipid synthesis.
How is HMG-CoA reductase activated?
Regulation of HMG-CoA Reductase First by regulation of transcription of the reductase gene, which is activated by sterol regulatory element binding protein, a protein that binds to the promoter of the HMGR gene when cholesterol levels fall.
How is HMG-CoA reductase inhibited?
Statins competitively inhibit the HMG-CoA reductase enzyme. Statins bind to the active site of the enzyme and change its structure. As the structure of the enzyme is changed, it cannot bind with the receptor, thus its activity is reduced.
What is the SREBP pathway?
The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 1997;89(3):331–340. doi: 10.1016/S0092-8674(00)80213-5.
Is lanosterol a specific regulator of SREBP-2 cleavage?
DOI: 10.1194/jlr.RA119000201 Abstract Sterol-regulated HMG-CoA reductase (HMGCR) degradation and SREBP-2 cleavage are two major feedback regulatory mechanisms governing cholesterol biosynthesis. Reportedly, lanosterol selectively stimulates HMGCR degradation, and cholesterol is a specific regulator of SREBP-2 cleavage.
Is the SREBP pathway involved in Xanthophyllomyces dendrorhous astaxanthin production?
The SREBP pathway in X. dendrorhous Xanthophyllomycesdendrorhousproduces the carotenoid astaxanthin and a carotenoid overproduction phenotype was observed in an ergosterol biosynthesis mutant, which was one of the first evidence that suggested that carotenoid production in this yeast could be regulated, at least in part, by the SREBP pathway.
How are SREBPs regulated?
Besides proteolytic activation, SREBPs are regulated by covalent modifications and by interaction with other proteins. This has been studied more in mammals than in fungi. In mammals, regulation of SREBP by phosphorylation-dependent degradation has been reported [56, 57].