bromination of cholesterol mechanism

(NPC1). Sundqvist, A. et al. & Dong, X. C. FoxO3 transcription factor and Sirt6 deacetylase regulate low density lipoprotein (LDL)-cholesterol homeostasis via control of the proprotein convertase subtilisin/kexin type 9 (Pcsk9) gene expression. A central regulator ofenergy homeostasis that is activated when the cellular ATP level is low. This work shows that the ER protein INSIG1 binds to the SCAPSREBP complex in the presence of sterols and mediates its negative feedback regulation of cholesterol synthesis. Gastroenterology 152, 11261138 (2017). Wang, J. et al. 18, 15681574 (1998). 16 April 2023, Access Nature and 54 other Nature Portfolio journals, Get Nature+, our best-value online-access subscription, Receive 12 print issues and online access, Get just this article for as long as you need it, Prices may be subject to local taxes which are calculated during checkout. The dibromocholesterol should crystalize out as a a plastic white paste. Res. PubMedGoogle Scholar. Proc. Biol. Chem. You'll get a detailed solution from a subject matter expert that helps you learn core concepts. Repa, J. J., Buhman, K. K., Farese, R. V., Dietschy, J. M. & Turley, S. D. ACAT2 deficiency limits cholesterol absorption in the cholesterol-fed mouse: impact on hepatic cholesterol homeostasis. Cell Metab. Zhang, D. Q. et al. Chem. Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Acta 1771, 12161225 (2007). Experiments have shown that when the alkane and halogen reactants are not exposed . Arterioscler. Nature 533, 561564 (2016). Poirier, S. et al. wrote the Review and H.Y. Insulin induces human acyl-coenzyme A:cholesterol acyltransferase1 gene expression via MAP kinases and CCAAT/enhancer-binding protein . J. Distinct functional domains contribute to degradation of the low density lipoprotein receptor (LDLR) by the E3 ubiquitin ligase inducible degrader of the LDLR (IDOL). 285, 3349933509 (2010). 276, 3943839447 (2001). Weinglass, A. Mol. Yang, L. et al. eLife 4, e05560 (2015). J. Lipid Res. The authors thank Lu-Yi Jiang and Yun-Feng Li for drafting the original figures. Purpose This reaction involves nucleophilic attack by the alkene on bromine, forming a tertiary carbocation with bromonium ion character. The largest type of E3 ubiquitin ligases with the RING (really interesting new gene) finger domains that bind two zinc ions in a unique cross-brace arrangement through a defined motif of cysteine and histidine residues. Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8. & van de Sluis, B. PLOS ONE 9, e109886 (2014). Chem. J. Biol. Sorrentino, V. et al. Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism. 107, 163171 (2001). 29, 12351241 (2009). Natl Acad. Cell 11, 36753687 (2000). 290, 2346423477 (2015). Trends Biochem. 20, 910918 (2014). Cell 169, 12281239 (2017). Proc. PubMed Myeloid Acat1/Soat1 KO attenuates pro-inflammatory responses in macrophages and protects against atherosclerosis in a model of advanced lesions. This study shows that hepatic ABCG5 and ABCG8 mediates cholesterol excretion into bile and that intestinal ABCG5 and ABCG8 contributes to cholesterol efflux via the non-hepatobiliary route. Neufeld, E. B. et al. Chem. Google Scholar. Disturbed cholesterol balance underlies not only cardiovascular disease but also an increasing number of other diseases such as neurodegenerative diseases and cancers. USA 108, 2010720112 (2011). This study shows that IDOL is differentially expressed in mice and non-human primates, and that activation of the LXRIDOL pathway reduces hepatic LDLR protein and elevates plasma LDL levels in non-human primates. Cancer Res. Chem. Intestinal CREBH overexpression prevents high-cholesterol diet-induced hypercholesterolemia by reducing Npc1l1 expression. 3, 1524 (2006). Genomics 65, 137145 (2000). 59, 749763 (2018). microRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo. Chem. The first sterol intermediate inthe mevalonate pathway consisting of 30 carbons. The core of a sphingolipid is an amino alcohol called sphingosine. Google Scholar. Arterioscler. Structure and inhibition mechanism of the catalytic domain of human squalene epoxidase. Soto-Acosta, R., Bautista-Carbajal, P., Cervantes-Salazar, M., Angel-Ambrocio, A. H. & del Angel, R. M. DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: apotential antiviral target. NPC1L1-deficient mice absorb much less cholesterol and are insensitive to ezetimibe, a cholesterol absorption inhibitor. Hepatocyte nuclear factor 1 plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine. Am. J. Biol. J. Biol. Proc. Effects of acceptor composition and mechanism of ABCG1-mediated cellular free cholesterol efflux. Biophys. 54, 21742184 (2013). 811, 7486 (2017). USA 100, 1202712032 (2003). This article provides a historical overview and the latest theory on SCAP and the SREBP pathway. Extracellular loop C of NPC1L1 is important for binding to ezetimibe. Chem. Vance, J. E. & Karten, B. NiemannPick C disease and mobilization of lysosomal cholesterol by cyclodextrin. Laden, B. P., Tang, Y. 18, 361374 (2017). Sato, R., Goldstein, J. L. & Brown, M. S. Replacement of serine-871 of hamster 3-hydroxy-3-methylglutaryl-CoA reductase prevents phosphorylation by AMP-activated kinase and blocks inhibition of sterol synthesis induced by ATP depletion. Ufd1 is a cofactor of gp78 and plays a key role in cholesterol metabolism by regulating the stability of HMG-CoA reductase. Intrathecal 2-hydroxypropyl--cyclodextrin in a single patient with NiemannPick C1. Chem. Biochem. Sci. 59, 21812187 (2018). J. Physiol. Modulation of human NiemannPick C1-like 1 gene expression by sterol: role of sterol regulatory element binding protein 2. Xie, C., Li, N., Chen, Z. J., Li, B. L. & Song, B. L. The small GTPase Cdc42 interacts with NiemannPick C1-like 1 (NPC1L1) and controls its movement from endocytic recycling compartment to plasma membrane in a cholesterol-dependent manner. Cell. 13, 771782 (2006). Proc. Cell Biol. Cell Biol. This This problem has been solved! Dissection of the endogenous cellular pathways of PCSK9-induced low density lipoprotein receptor degradation: evidence for an intracellular route. Metab. EMBO J. The membrane vesicles coated by coatomer II (COP II), which is a type of vesicle coat protein that facilitates the formation of transport vesicles from the endoplasmic reticulum (ER). Biochem. 295, 276282 (2002). Cardiol. Commun. & Dietschy, J. M. Multiple mechanisms limit the accumulation of unesterified cholesterol in the small intestine of mice deficient in both ACAT2 and ABCA1. Science 325, 100104 (2009). Rev. Alrefai, W. A. et al. Membrane cholesterol efflux drives tumor-associated macrophage reprogramming and tumor progression. J. Biol. Li, T. et al. (SIRT1). The N-terminal domain of NPC1L1 protein binds cholesterol and plays essential roles in cholesterol uptake. Mol. Overexpression of cholesterol 7-hydroxylase promotes hepatic bile acid synthesis andsecretion and maintains cholesterol homeostasis. & Ioannou, Y. ISSN 1471-0072 (print). Cholesterol-regulated translocation of NPC1L1 to the cell surface facilitates free cholesterol uptake. The cellular cholesterol level reflects the dynamic balance between biosynthesis, uptake, export and esterification a process in which cholesterol is converted to neutral cholesteryl esters either for storage in lipid droplets or for secretion as constituents of lipoproteins. (LCAT). Mol. Jiang, L. Y. et al. J. Biol. Chem. Cell 11, 2533 (2003). Natl Acad. Abstraction of hydrogen by a bromine atom is endothermic in both cases. Out, R. et al. Costet, P., Luo, Y., Wang, N. & Tall, A. R. Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. The IDOLUBE2D complex mediates sterol-dependent degradation of the LDL receptor. Ezetimibe inhibits cholesterol uptake by blocking the endocytosis of NPC1L1. Liver Physiol. Natl Acad. Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2 encoded by ABCG5 and ABCG8 respectively. Bromination was the method chosen to remove traces of 3B-cholestanol, 7-cholesten-3b-ol, and 5,7-cholestadien-3B-ol that were assumed to be present in the sample used. Giandomenico, V., Simonsson, M., Gronroos, E. & Ericsson, J. Coactivator-dependent acetylation stabilizes members of the SREBP family of transcription factors. The cholesterol C=C and the cholesterol dibromide C-Br is one way to show it worked. USA 108, 551556 (2011). PubMed Nature 548, 352355 (2017). NPC1 is ubiquitously expressed and localizes on lysosomal membrane. Nowaczyk, M. J. M. & Irons, M. B. SmithLemliOpitz syndrome: phenotype, natural history, and epidemiology. Schoebel, S. et al. eLife 8, e44396 (2019). J. Lipid Res. Sitosterolemia: diagnosis, investigation, and management. Parini, P. et al. Sci. Kennedy, M. A. et al. Kim, Y. C. et al. Res. J. Biol. J.L. Luo, J., Jiang, L., Yang, H. & Song, B. L. Routes and mechanisms of post-endosomal cholesterol trafficking: a story that never ends. 293, 312323 (2018). Peterson, T. R. et al. Scotti, E. et al. Google Scholar. USA 99, 1275312758 (2002). Seidah, N. G., Chretien, M. & Mbikay, M. The ever-expanding saga of the proprotein convertases and their roles in body homeostasis: emphasis on novel proprotein convertase subtilisin kexin number 9 functions and regulation. A protein that binds lipids to form lipoproteins, which then transport lipids and fat-soluble vitamins in circulation. A family of two ubiquitously expressed, membrane-associated proteins, namely, flotillin 1 and flotillin 2. Curr. Arterioscler. Natl Acad. A metabolite of vitamin A1 (all-trans-retinol). AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell. 286, 3593335942 (2011). Du, X. et al. Cellular localization and trafficking of the human ABCG1 transporter. Biochim. 371, 20722082 (2014). Cell 89, 331340 (1997). Circ. Horton, J. D., Goldstein, J. L. & Brown, M. S. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. They participate in the regulation ofmetabolism and growth. & Ye, J. Proteasomal degradation of ubiquitinated Insig proteins is determined by serine residues flanking ubiquitinated lysines. The sterol transporting heterodimer ABCG5/ABCG8 requires bile salts to mediate cholesterol efflux. Open Access Lipogenic transcription factor ChREBP mediates fructose-induced metabolic adaptations to prevent hepatotoxicity. Tao, R. Y., Xiong, X. W., DePinho, R. A., Deng, C. X. Nat. A. Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interactswith AP-2. Hong, C. et al. Cell Metab. 116, 29953005 (2006). volume21,pages 225245 (2020)Cite this article. Recombinant acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) purified toessential homogeneity utilizes cholesterol in mixed micelles or in vesicles in a highly cooperative manner. 316, C559C566 (2019). Acta Mol. Biology 3, 781800 (2014). Sci. 44, 273292 (2019). Bromination of Cholesterol Mechanism. Cholesterol is superior to 7-ketocholesterol or 7-hydroxycholesterol as an allosteric activator for acyl-coenzyme A:cholesterol acyltransferase 1. Mol. Nat Rev Mol Cell Biol 21, 225245 (2020). Jinjin Ma. 13, 260273 (2011). Nat. 87, 783807 (2018). Ablation of gp78 in liver improves hyperlipidemia and insulin resistance by inhibiting SREBP to decrease lipid biosynthesis. Bromination of an alkene by N-bromosuccinimide (NBS) in the presence of light or peroxide is a radical reaction and produces an allylic bromide. Experiment 5 - Bromination of Cholesterol. 286, 2508825097 (2011). J. Biol. Natl Acad. Article J. Med. & Porter, T. D. Cloning, heterologous expression, and enzymological characterization of human squalene monooxygenase. 31, 11081115 (2011). After filtration from the mother liquor, the cholesterol dibromide was theoretically stripped of all its original impurities. Davis, H. R. et al. Liu, J., Chang, C. C., Westover, E. J., Covey, D. F. & Chang, T. Y. This study suggests that competitive oxidation and ubiquitylation of Cys is a new mechanism of sensing ROS. Kobayashi, A. et al. 279, 2291322925 (2004). 11, 367383 (2012). Chem. Natl Acad. Heat shock protein 90 modulates lipid homeostasis by regulating the stability and function of sterol regulatory element-binding protein (SREBP) and SREBP cleavage-activating protein. Gut microbiota metabolism of anthocyanin promotes reverse cholesterol transport inmice via repressing miRNA-10b. Debromination of 473 and 468 was achieved by heating with sodium sulfite in aqueous solution to give 456 (1987ACSA(B)724).The 4,5-dibromo compound 476 was debrominated regioselectively furnishing the 4-bromo compound 473 (1987ACSA(B)724).The regioselectivity reflects that the 5-anion 475 according to H/D exchange rates is formed faster than the 4-anion 474 (Scheme 138). J. Das, A., Davis, M. A. 6, 8100 (2015). Proc. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in 1, 179189 (2005). Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. A class of lipids with a polar head group and two non-polar tails. J. Biomed. Lipidol. Ezetimibe added to statin therapy after acute coronary syndromes. Proc. Chem. Biophys. 116, 7579 (2015). 119, 827838 (2016). J. Biol. Acta 1821, 547551 (2012). Comparative genome analysis of potential regulatory elements in the ABCG5ABCG8 gene cluster. 56, 447467 (2016). Kotzka, J. et al. Goldstein, J. L. & Brown, M. S. Regulation of the mevalonate pathway. 288, 2925229259 (2013). 290, 2753327544 (2015). Su, Y. R. et al. Deficiency of acyl CoA:cholesterol acyltransferase 2 prevents atherosclerosis in apolipoprotein E-deficient mice. Kuzu, O. F., Noory, M. A. Nelson, J. K. et al. Nguyen, T. M. et al. Biol. Biol. 282, 1860218612 (2007). Proc. Silvente-Poirot, S. & Poirot, M. Cholesterol and cancer, in the balance. 13, 376388 (2011). microRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. The clathrin adaptor proteins ARH, Dab2, and numb play distinct roles in NiemannPick C1-Like 1 versus low density lipoprotein receptor-mediated cholesterol uptake. Zelcer, N. et al. 10, 97 (2019). 289, 1905319066 (2014). J. Biol. To debrominate cholesterol, 20 mL of t-butylmethyl ether, 5 mL of acetic acid and 0.2 g of Zn dust were added into the Erlenmeyer flask containing the dibromocholesterol solid. Mol. Article Res. In the present experiment, it is employed for the very practical purpose of purifying crude cholesterol through the process of bromination, crystallization, and then zinc dust debromination. Am. LXRs promote cholesterol efflux mainly by upregulating ATP-binding cassette (ABC) subfamily A member 1 (ABCA1) and ABC subfamily G member 1 (ABCG1), ABCG5 and ABCG8. Chem. Continuous transport of a small fraction of plasma membrane cholesterol to endoplasmic reticulum regulates total cellular cholesterol. 156, 227236 (2000). Pharmacokinet. 310, G618G628 (2016). Int. & DeBose-Boyd, R. A. Geranylgeranyl-regulated transport of the prenyltransferase UBIAD1 between membranes of the ER and Golgi. It is biosynthesized by all mammalian cells and predominantly localizes to cell membranes, where it interacts with the adjacent lipids to regulate rigidity, fluidity and permeability of the. Also known as ubiquitin-conjugating enzyme. 25. 14, 413419 (2007). Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol. Natl Acad. Lipidol. Drug Metab. Luu, W., Sharpe, L. J., Capell-Hattam, I., Gelissen, I. C. & Brown, A. J. Oxysterols: old tale, new twists. Chem. Song, B. L., Javitt, N. B. INSIG proteins, including INSIG1 and INSIG2, are integral membrane proteins of the endoplasmic reticulum that mediate sterol regulation of sterol regulatory element-binding protein cleavage-activating protein (SCAP) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase). Cholesterol homeostasis is vital for proper cellular and systemic functions. Natl Acad. Genet. Cholesterol homeostasis is vital for proper cellular and systemic functions. Annu. Consult your lecture text.] Opin. Edit 2 I remembered some brominations on dimethoxy-substituted hydroxymethylnaphthalines I did back in the days. 1, 379391 (2005). Commun. Goldstein, J. L. & Brown, M. S. The LDL receptor. Qian, H. et al. Cholesterol is an essential component of cell membranes and the precursor for the synthesis of steroid hormones and bile acids. Yu, C. et al. Intracisternal cyclodextrin prevents cerebellar dysfunction and Purkinje cell death in feline NiemannPick type C1 disease. FERM-dependent E3 ligase recognition is a conserved mechanism for targeted degradation of lipoprotein receptors. Res. 49, 17701781 (2008). Biol. Thekey factors governing these pathways and the major mechanisms by which they respond tovarying sterol levels are described. Natl Acad. & Chang, T. Y. Pub Date: June 2003 DOI: 10.1021/ed080p670 Bibcode: 2003JChEd..80..670G . Jakulj, L. et al. Differential use of E2 ubiquitin conjugating enzymes for regulated degradation of the rate-limiting enzymes HMGCR and SQLE in cholesterol biosynthesis. Heparan sulfate proteoglycans present PCSK9 to the LDL receptor. Rayner, K. J. et al. J. Hum. PubMed Chem. Science 328, 15701573 (2010). Sci. Sci. Cooperative interaction between hepatocyte nuclear factor 4 and GATA transcription factors regulates ATP-binding cassette sterol transporters ABCG5 and ABCG8. Struct. Chua, N. K., Howe, V., Jatana, N., Thukral, L. & Brown, A. J. Chem. Nuclear factor-B regulates the expression of multiple genes encoding liver transport proteins. Rep. 8, 9006 (2018). An adaptor protein that binds low-density lipoprotein receptor and mediates its endocytosis in hepatocytes and lymphocytes. Z. Insig-dependent ubiquitination anddegradation of mammalian 3-hydroxy-3-methylglutaryl-CoA reductase stimulated by sterolsand geranylgeraniol. Arterioscler. J. Biol. Song, B. L. & DeBose-Boyd, R. A. Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase stimulated by - and -tocotrienols. Song, B. L., Sever, N. & DeBose-Boyd, R. A. gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase. Repa, J. J. et al. & Dong, X. C. Hepatic SREBP-2 and cholesterol biosynthesis are regulated by FoxO3 and Sirt6. Back, S. S. et al. J. Biol. Chem. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. USA 105, 18201825 (2008). 372, 23872397 (2015). Opin. The bromination of a double bond is an important and well-understood reaction. Thank you for visiting nature.com. Cell Metab. Biochim. Cell. Lee, P. C. W., Sever, N. & DeBose-Boyd, R. A. Rev. Science 303, 12011204 (2004). Iwayanagi, Y., Takada, T. & Suzuki, H. HNF4 is a crucial modulator of the cholesterol-dependent regulation of NPC1L1. Adi, D. et al. Open Access Sci. 53, 95104 (2012). Proc. Genet. Biophys. In most cases, FBPs recognize phosphorylated proteins. Nature 531, 651655 (2016). USA 114, 79998004 (2017). Escola-Gil, J. C. et al. Biol. 151, 102107 (2015). Natl Acad. Arterioscler. Foam cells promote the atherosclerotic plaque build-up and inflammation during atherosclerosis. Structure of the human lipid exporter ABCA1. & Shimano, H. Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice. Endocrinol. Small heterodimer partner and fibroblast growth factor 19 inhibit expression of NPC1L1 in mouse intestine and cholesterol absorption. Plasma cholesteryl esters provided by lecithin: cholesterol acyltransferase and acyl-coenzyme A:cholesterol acyltransferase 2 have opposite atherosclerotic potential. Sci. Tveten, K. et al. This study identifies direct SREBP targets through systematically analysing genes differentially expressed in mice overexpressing Srebp1a or Srebp2, or lacking Scap. Li, P. S. et al. The transition states are more product-like and possess more radical character; therefore, the difference in radical stability is more strongly expressed, and E a c t is larger. TNF- stimulates the ACAT1 expressionin differentiating monocytes to promote the CE-laden cell formation. A Mechanism for Electrophilic Substitution Reactions of Benzene A two-step mechanism has been proposed for these electrophilic substitution reactions. Kennedy, M. A. et al. Sci. Nguyen, T. M., Sawyer, J. K., Kelley, K. L., Davis, M. A. Theyplay a role in forming cholesterol-rich membrane microdomains, endocytosis and signal transduction. 55, 16091621 (2014). DISCUSSION. Lee, J. N., Gong, Y., Zhang, X. Y. 41, 457463 (2016). Regulated endoplasmic reticulum-associated degradation of a polytopic protein p97 recruits proteasomes to Insig-1 before extraction from membranes. Cholesterol increases protein levels of the E3 ligase MARCH6 and thereby stimulates protein degradation. They transport ubiquitylated cargo to cellular vesicles by promoting membrane budding into the endosomes to form multivesicular bodies, which eventually fuse with lysosome and cause degradation ofthecargo. & Edwards, P. A. ATP binding cassette transporter G1 (ABCG1) is an intracellular sterol transporter. Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. Annu. J. Biol. Med. 29, 144150 (2018). In the meantime, to ensure continued support, we are displaying the site without styles Biddinger, S. B. et al. Xiao, X. et al. Blom, D. J. et al. 291, 48134825 (2016). Chem. Chem. 295, 7480 (2002). Nature Reviews Molecular Cell Biology thanks N. Ridgway and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Chem. 277, 1879318800 (2002). Thromb. Cell 110, 489500 (2002). Circ. Maxfield, F. R. & van Meer, G. Cholesterol, the central lipid of mammalian cells. The authors declare no competing interests. 31, 18851893 (2011). & DeBose-Boyd, R. A. Sequential actions of the AAA-ATPase valosin-containing protein (VCP)/p97 and the proteasome 19S regulatory particle in sterol-accelerated, endoplasmic reticulum (ER)-associated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. NiemannPick C1 like 1 protein is critical for intestinal cholesterol absorption. Biol. 260, 522530 (1985). Chang, T. Y., Li, B. L., Chang, C. C. & Urano, Y. Acyl-coenzyme A:cholesterol acyltransferases. 56, 963971 (2015). Am. de Boer, J. F. et al. Mol. Cell Dev. 26, 11971211 (2016). Melton, E. M. et al. Cell Metab. The complex that catalyses theubiquitylation of proteins for degradation. Hum. CAS Mechanisms and regulation ofcholesterol homeostasis. USA 102, 32423247 (2005). Zhang, J. H. et al. & Rudel, L. L. Identification of putative active site residues of ACAT enzymes. Jo, Y., Lee, P. C. W., Sguigna, P. V. & DeBose-Boyd, R. A. Sterol-induced degradation of HMG CoA reductase depends on interplay of two Insigs and two ubiquitin ligases, gp78 and Trc8. Front. Takahashi, Y. 36, 285294 (2016). Chem. Nat. 289, 2402024029 (2014). New insights into cellular cholesterol acquisition: promoter analysis of human HMGCR and SQLE, two key control enzymes in cholesterol synthesis. Rev. 102, 113120 (2008). Biol. Proteins with glycosylphosphatidylinositol (GPI) attached at the C-termini. Natl Acad. Commun. Biol. 275, 2808328092 (2000). Rosenson, R. S. et al. 279, 3358633592 (2004). Pramfalk, C., Davis, M. A., Eriksson, M., Rudel, L. L. & Parini, P. Control of ACAT2 liver expression by HNF1. Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP. Chem. Thromb. Transcriptional control of intestinal cholesterol absorption, adipose energy expenditure and lipid handling by Sortilin. Lee, J. P. et al. Lanosterol is synthesized by cyclization of squalene and can potently stimulate degradation of hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) without inhibiting the processing of sterol regulatory element-binding protein (SREBP). Mol. Natl Acad. Radhakrishnan, A., Goldstein, J. L., McDonald, J. G. & Brown, M. S. Switch-like control of SREBP-2 transport triggered by small changes in ER cholesterol: a delicate balance. Intramembrane aspartic acid inSCAP protein governs cholesterol-induced conformational change. Table of Content Types of Bromination Bromination via a Free Radical Mechanism Bromination via an Addition Reaction Cell 165, 14671478 (2016). Biochemistry 41, 37623769 (2002). Kwon, H. J., Lagace, T. A., McNutt, M. C., Horton, J. D. & Deisenhofer, J. Molecular basis for LDL receptor recognition by PCSK9. Role of the N-terminal hydrophilic domain of acyl-coenzyme A:cholesterol acyltransferase 1 on the enzymes quaternary structure and catalytic efficiency. Yu, L. et al. 7, 276ra26 (2015). This is a preview of subscription content, access via your institution. China Life Sci. Mol. 273, 3513235141 (1998). Nagata, K. O., Nakada, C., Kasai, R. S., Kusumi, A. Zhang, D. W., Garuti, R., Tang, W. J., Cohen, J. C. & Hobbs, H. H. Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor. Luo, J., Yang, H. & Song, BL. J. Clin. Morris, S. M. & Cooper, J. J. AMPK activation inhibits cholesterol and fatty acid synthesis. 203, 427436 (2013). The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1. Istvan, E. S., Palnitkar, M., Buchanan, S. K. & Deisenhofer, J. 370, 18091819 (2014). Sci. VLDLs are converted to intermediate-density lipoproteins and low-density lipoproteins inthe bloodstream. Med. Proc. Horie, T. et al. Chem. Chem. Med. Song, B. L. et al. revised it. Chem. Opin. CAS 29, 17181722 (2009). Traffic 2, 111123 (2001). Atheroscler. CAS Lu, K. et al. In this Review, we discuss the latest advances regarding how each of the four parts of cholesterol metabolism is executed and regulated. Nagai, M., Sakakibara, J., Nakamura, Y., Gejyo, F. & Ono, T. SREBP-2 and NF-Y are involved in the transcriptional regulation of squalene epoxidase. Ge, L. et al. Wang, Y., Huang, Y., Hobbs, H. H. & Cohen, J. C. Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR. 5, 10921102 (2016). This study identifies that mutations in the ARH gene cause a different form of hypercholesterolaemia from that caused by LDLR deficiency in humans. Oncogene 35, 63786388 (2016). Proc. Bromination -nucleophilic attack by the alkene on bromine - forming a tertiary carbocation with bromonium ion character .-ion is attacked from the backside by bromide ion to form dibromocholesterol in the trans and diaxial configuration -practical purpose of purifying cholesterol. A diterpene alcohol containing 20 carbons that is synthesized in the mevalonate pathway. Lee, J. Y. et al. p53 represses the mevalonate pathway to mediate tumor suppression. Gustafsen, C. et al. (AMP-activated protein kinase). EMBO J. Natl Acad. Provided by the Springer Nature SharedIt content-sharing initiative, Journal of Animal Science and Biotechnology (2023), Nature Reviews Molecular Cell Biology (Nat Rev Mol Cell Biol) Brown, M. S., Radhakrishnan, A.

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