Selective lipid uptake

Liu B. and Krieger M. (2002) Highly purified scavenger receptor class B, type I reconstituted into phosphatidylcholine/cholesterol liposomes mediates high affinity high density lipoprotein binding and selective lipid uptake. J. Biol. Chem. 277, 34125-34135. 

Export by ABC proteins endocytosis/exocytosis as part of lipoproteins import by selective lipid uptake from lipoproteins... 

NPCl) protein 753 receptor SR-Bl 763 receptor-mediated endocytosis 760 reverse cholesterol transport 771 selective lipid uptake 760 SRE-binding protein (SREBP) 764 statin 773... 

The first entirely synthetic derivative, fluvastatin (see Ref. [19]), and its subsequent derivative, atorvastatin, have a lipid solubility that is intermediate between pravastatin and the lactone prodrugs (see Tab. 4.2), and consequently their liver specificities are less expressed. In order to benefit from selective statin uptake mechanism into the liver cells and thereby decrease passive diffusion into other cell types, the recently introduced rosuvastatin molecule was purposefully made more hydrophilic by the introduction of a sulfonamide group. Indeed, the ratio of IC5 values measured in fibroblasts and hepatocyte cultures became considerable higher than that of atorvastatin (see Tab. 4.1). The pronounced differences of inhibitory potency, lipophilicity and the extent of active OATP-linked transport jointly... 

During, A. et al.. Carotenoid uptake and secretion by Caco-2 cells 3-carotene isomer selectivity and carotenoid interactions, J. Lipid. Res., 43, 1086, 2002. 

This permeability barrier shows selectivity in that small hydrophobic molecules can partition into and diffuse across the lipid bilayer of the cell membrane, whereas small hydrophilic molecules can only diffuse between cells (i.e., through the intercellular junctions). In addition, the presence of uptake and efflux transporters complicates our ability to predict intestinal permeability based on physicochemical properties alone because transporters may increase or decrease absorptive flux. The complexity of the permeability process makes it difficult to elucidate permeability pathways in complex biological model systems such as animals and tissues. For this reason, cultured cells in general, and Caco-2 cells in particular, have been used extensively to investigate the role of specific permeability pathways in drug absorption. 

The HDL lipids are removed from the circulation by a selective uptake and by an indirect pathway. The selective uptake of cholesterol esters from HDL into he-patocytes and steroidogenic cells is mediated by the binding of HDL to scavenger receptor B1 (SR-BI). This selective uptake by SR-BI may depend on the presence of cofactors such as HL, which hydrolyses phospholipids on the surface of both HDL and plasma membranes and thereby enables the flux of cholesteryl esters from the lipoprotein core into the plasma membrane [42]. The indirect pathway involves the enzyme CETP, which exchanges cholesteryl esters of a-HDL with triglycerides of chylomicrons, VLDL, IDL, and LDL. The a-HDL derived cholesteryl esters are therefore removed via the LDL-receptor pathway. The removal of excess cholesterol from the periphery and the delivery to the liver for excretion in the bile is termed reverse cholesterol transport. 

The discriminative uptake of alkali metal cations by biological systems, through their membranes, has been an area of much interest. In the membrane, the cations must pass through a lipid bilayer of low dielectric constant and this has led to the proposition that the cation could be selectively transferred via a carrier molecule, or through a suitably donor-lined pore.7-9 As a consequence of their selective properties, the polyethers and cryptands have been investigated as speculative models for the above process and selectivity sequences have been established. 

Camarota, L. M., Chapman, J. M., Hui, D. Y., and Howies, P. N. (2004) Carboxyl ester lipase coffactionates with scavenger receptor BI in hepatocyte lipid rafts and enhances selective uptake and hydrolysis of cholesteryl esters from HDL3. J. Biol. Chem. 279, 27599-27606. 

Several carrier systems have been shown to be present in the brain endothelium, allowing for the selective transport of a group of common substrates (Table 13.1). The most common system is the one that mediates the transport of glucose, which provides the brain with virtually all its energy. Carrier-mediated mechanisms are also responsible for the absorption of two other energy sources ketone bodies, which are derived from lipids, and lactic acid, a by-product of sugar metabolism. Carrier-mediated transport systems are also involved in the uptake of amino acids by the brain. The brain can manufacture its own small neutral and acidic amino acids however, large neutral and basic amino acids are obtained from the bloodstream. 

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