Cholesterol translocation

Li G, Gu HM, Zhang DW (2013) ATP-binding cassette transporters and cholesterol translocation. IUBMB Life 65 505-512... 

Porn, M. I., Tenhunen, J., and Slotte, J. P. (1991). Increased steroid hormone secretion in mouse Leydig tumor cells after induction of cholesterol translocation by sphingomyelin degradation. Biochim Biophys Acta 1093, 7-12. 

LDL (apo B-lOO, E) receptors occur on the cell surface in pits that are coated on the cytosolic side of the cell membrane with a protein called clathrin. The glycoprotein receptor spans the membrane, the B-lOO binding region being at the exposed amino terminal end. After binding, LDL is taken up intact by endocytosis. The apoprotein and cholesteryl ester are then hydrolyzed in the lysosomes, and cholesterol is translocated into the cell. The receptors are recycled to the cell surface. This influx of cholesterol inhibits in a coordinated manner HMG-CoA synthase, HMG-CoA reductase, and, therefore, cholesterol synthesis stimulates ACAT activ-... 

ABCA1 functions to translocate cholesterol and phospholipids outward across the plasma membrane after their delivery to the inner plasma membrane leaflet via vesicular pathways [35]. This occurs in astrocytes and developing neurons. Astrocytes also secrete apoE. Extracellular apoE binds and interacts with ABCA1 to promote cholesterol and PC efflux from cultured astrocytes through a mechanism that results in apoE-stabilized... 

Allen-Vercoe, E., Waddell, B., Livingstone, S., Deans, J., and DeVinney, R. (2006). Entero-pathogenic Escherichia coli Tir translocation and pedestal formation requires membrane cholesterol in the absence of bundle-forming pili. Cell. Microbiol. 8, 613-624. 

Lipids and proteins can shift easily within one layer of a membrane, but switching between the two layers ( flip/flop") is not possible for proteins and is only possible with difficulty for lipids (with the exception of cholesterol). To move to the other side, phospholipids require special auxiliary proteins (translocators, flipases ). 

Figure 15-2. A simplified schematic of cholesterol transport. Cholesterol travels to non-hepatic cells, such as the macrophage, via VLDL and LDL particles, while excess cholesterol is shuttled to the liver via HDL particles. Note that AHCAl mediates nascent HDL formation by translocating cellular cholesterol and phospholipids to apolipoprotein A-I (apoA-I) in an active, energy-dependent reaction. CETP, cholesteryl ester transfer protein LCAT, lecithinxholesterol acyltransferase LDLR, low-density lipoprotein receptor SR-B1, scavenger receptor Bl.

The lipids in a lipid bilayer may translocate across the bilayer from one monolayer to the apposed monolayer. This transmembrane translocation process, which is also known as flip-flop, is slow for lipids with large polar head groups such as glyc-erolipids and sphingophospholipids but can be fast in the case of lipids with very small polar moieties such as cholesterol. Typical first-order rate constants for transmembrane translocation of a phospholipid-like molecule in liquid-disordered phase bilayers prepared from l-palmitoyl-2-oleoylphosphatidylcholine (POPC) are s and may be about 10-fold slower in... 

La liquid-ordered phase bilayers prepared from binary mixtures of the same phosphatidylcholine and cholesterol but is much slower ( 10 s ) in Lx liquid-ordered phase membranes prepared from sphingomyelin and cholesterol (55). The activation free energy for the process, which corresponds to the energy necessary to put the translocating lipid molecule at the bilayer mid-plane, is 100kJmol In contrast, the rate constant for transmembrane translocation of cholesterol may be 1 s (56). 

A reduction in the cholesterol level due to lactulose was observed by N. Ebner in 1973 and confirmed by D. Conte etal. in 1977. Lactulose can also be used in hepatogenic disturbances of lipid metabolism. Translocation of... 

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