Sterol response element binding protein SREBP

The concentration of LDL-cholesteroi in the blood is a function of its rate of production and rate of removal from the bloixistream. Diet influences LDL-cho-lesterol by changing its rate of removal or clearance, according to the following scenario. Let us briefly return to the topics of proteins and DMA, A transcription factor called sterol response element binding protein (SREbP) binds to a stretch of DNA called the sterol response element. The sterol response element has the structure CACCCCAC. In discussing any sequence of DNA, it is conventional to... 

Sterol-response element-binding proteins (SREBPs) are transcription factors that coor-dinately increase the synthesis of fatty acids and cholesterol (Chapters 6, 7, and 14). The transcriptionally active forms of SREBPs are generated from precursor proteins by a sterol-dependent proteolytic cleavage [8]. Several studies have indicated that an increased production of transcriptionally active SREBPs stimulates VLDL secretion. 

Sterol responsive element binding protein (SREBP)... 

Members of a family of nuclear transcription factors called sterol regulatory element-binding proteins (SREBP) are responsible for the regulation of these cholesterol feedback mechanisms. SREBP are able to activate a number of genes encoding for proteins involved in the homeostasis of cholesterol and other lipids, including the LDL receptor gene itself. 

SREBP Sterol response element binding protein... 

Abbreviations FASN, fatty acid synthase ACC, acetyl-CoA-carboxylase ACL, ATP-citrate lyase NADPH, nicotinamide adenine dinucleotide phosphate MAT, malonyl acetyl transferases KS, ketoacyl synthase KR, p-ketoacyl reductase DH, p-hydroxyacyl dehydratase ER, enoyl reductase TE, thioesterase ACP, acyl carrier protein VLCFA, very long chain fatty acids ELOVL, elongation of very long chain fatty acids SCDl, stearoyl-CoA desaturase-1 AMPK, AMP-activated kinase ME, malic enzyme FASKOL, liver-specific deletion of FAS PPARa, Peroxisome Proliferator-Activating Receptor alpha HMG-CoA, 3-hydroxy-3-methyl-glutaryl-CoA SREBP, sterol response element binding protein SIP, site-one protease S2P, site-two... 

Fig. 12. Panel A Inhibitory effects of various polyunsaturated fatty acids (PUFA) on sterol regulatory element binding protein (SREBP)-lc promoter activity. EtOH, ethanol SA, saturated fatty acid OL, oleic acid LA, linoleic acid DHA, docosa-hexaenoic acid EPA, eicosapentaenoic acid AA, arachidonic acid. Panel B Mechanism by which polyunsaturated fatty acids suppress the SREBP-1 c promoter activity, through an effect on the liver X receptor (LXR)/9-c/s-retinoic acid receptor (RXR) activation pathway [redrawn from Yoshikawa etal. (129), reproduced with permission]. PUFA competitively interfere with binding of the endogenous ligand (possibly oxysterols) to LXR, thereby repressing LXR/RXR transactivity and SREBP-lc and lipogenic gene expression. Meanwhile, PUFA can bind and activate peroxisome proliferator activated receptor-a (PPARa) to induce 3-oxidation of fatty acids. PPRE PPAR response element LXRE LXR response element.

Fatty acid synthase is transcriptionally regulated by upstream stimulatory factor and sterol regulatory element binding protein Ic (SREBP-lc), in response to feeding/insulin. 

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