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. 2003 Jan 7;100(1):4-6.
doi: 10.1073/pnas.0237205100. Epub 2002 Dec 30.

Role of ABC transporters in secretion of cholesterol from liver into bile

Donald M Small  1
Affiliations

Role of ABC transporters in secretion of cholesterol from liver into bile

Donald M Small. Proc Natl Acad Sci U S A. .
No abstract available

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Figures

Figure 1
Figure 1
(A) When the bile salt secretion rate is high, BSEP (ABCB11) pumps bile salt from the cytoplasm into the cannilicular lumen at secretion rates 5–10 times the rate of PC secretion, i.e., in great excess. (B) PC are flipped from the cytoplasmic leaflet to the luminal side by MDR-2 (ABCB4). (C) Bile salts pick up PC that have been flipped to the outer leaflet either directly in contact with MDR-2 or from projections of PC from the luminal leaflet. (D) Bile salts and PC in the lumen combine to form small mixed PC-bile salt micelles. (E) These micelles collide with the ABC5G8 transporter, which projects cholesterol partly into the aqueous phase (the activated state shown with yellow halo), and the micelle captures it. (F) Mixed bile salt-PC-cholesterol micelles move down the biliary tract into the gallbladder and duodenum.
Figure 2
Figure 2
(A) Bile salt secretion is low because of physiologic interruption of the enteropatic circulation (e.g., fasting) or, in extreme cases, because of dysfunctional BSEP. (B) MDR-2 flips PC from the cytoplasmic to the luminal layer, where excess PC form projections into the lumen and then vesicles in close proximity to the cannilicular membrane (27). These vesicles may contain a small amount of cholesterol. (C) They could also pick up a small amount of activated cholesterol (yellow halo) from the membrane, but this process is very slow and probably unimportant. (D) Movement of cholesterol to the vesicle on collision with ABCG5G8 is greatly facilitated to the point where the vesicle becomes saturated at ≈1:1 cholesterol:PC. This result exceeds the micellar solubility of cholesterol (26) and creates a vesicular phase (liquid crystals) and the potential for cholesterol crystallization. (E) When the secretion rate of bile salts is relatively low, some micelles are formed, but most of the PC and cholesterol travels to the gallbladder in vesicular liquid crystalline form. In BSEP-null mice, where bile salt secretion is very low, the transfer of PC into vesicles and the movement of cholesterol into those vesicles from ABCG5G8 is enhanced, so that BSEP−/− mice actually secrete more PC and cholesterol than wild-type control (10).
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