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Comment
. 2004 Feb 20;303(5661):1149-50.
doi: 10.1126/science.1095519.

Biomedicine. Will the real cholesterol transporter please stand up

Eric L Klett  1 , Shailesh B Patel
Affiliations
Comment

Biomedicine. Will the real cholesterol transporter please stand up

Eric L Klett et al. Science. .
No abstract available

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Figures

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The absorption of dietary cholesterol and noncholesterol sterols
NPC1L1, expressed at the apical surface of enterocytes, may be the transporter that selectively absorbs dietary cholesterol (C) from micelles in the lumen of the small intestine, a step that is blocked by the drug ezetimibe. We propose a model for NPC1L1 action, in which this transporter permits the uptake of cholesterol (and noncholesterol sterols) into vesicles that then move through a subapical endosomal sorting compartment (6). Mutations in either of the transporters ABCG5 or ABCG8 cause the hyperabsorption of dietary plant sterols (PS) and other noncholesterol sterols from the small intestine, resulting in the human disease sitosterolemia (4, 5). The endosomal sorting compartment allows cholesterol to progress to the endoplasmic reticulum (ER), where it is esterified (CE) by ACAT-2 and then transferred to chylomicrons (pink) ready for secretion into the bloodstream; plant sterols are shunted through a pathway resulting in their transport back to the gut lumen via ABCG5 and ABCG8. Cholesterol that is synthesized de novo is also esterified by ACAT-2 and enters chylomicrons (7). Mutations in the microsomal triglyceride transfer protein (MTP) result in the human disorder abetalipoproteinemia characterized by secretion of chylomicrons (8). When bound to the protein disulfide isomerase, MTP transfers neutral lipids into newly formed chylomicrons in the ER, a necessary step in the pathway of lipid secretion. Mutations in the small guanosine triphosphatase (GTPase) Sar1, which is involved in trafficking of chylomicrons in the ER, causes chylomicron retention disease (9). Although no human disease has been linked to ARF-1 (ADP-ribosylation factor 1), this GTPase appears to be important for lipoprotein secretion by regulating vesicle budding from the Golgi (10). The parts played by SRB1 (scavenger receptor type B1), expressed on the apical and basolateral enterocyte surface, and ABCA1, expressed on the basolateral enterocyte surface, remain unclear. (TG, triglyceride; B48, apolipoprotein B48; HDL, high density lipoprotein.)
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References

    1. Schoenheimer R. Z Physiol Chem. 1929;180:1.
    1. Klett EL, et al. Curr Opin Lipidol. 2003;14:341. - PMC - PubMed
    1. Altmann SW, et al. Science. 2004;303:1201. - PubMed
    1. Berge KE, et al. Science. 2000;290:1771. - PubMed
    1. Lee MH, et al. Nature Genet. 2001;27:79. - PMC - PubMed

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