Mechanism of cellular fatty acid uptake.

circulation and represent an important, readily available energy source for certain organs like liver and heart. Controversy exists over how they are translocated across the plasma membrane [ 13. Since albumin is not taken up into the cells, only the dissociated unbound fatty acids are available for uptake. For evaluation of whether this uptake occurs by simple diffusion or facilitated transport, it was first examined whether fatty acids interact specifically with the plasma membrane. Therefore the binding characteristics of a representative long chain fatty acid, ['Hloleate, to isolated rat liver plasma membranes were analysed [2]. For these experiments oleate was complexed to albumin in various molar ratios which served to keep albumin in solution and to modulate the unbound oleate concentration in the medium. Saturable membrane binding characteristics were obtained with a K,, of 20 m i , indicating the presence of high affinity binding sites [2]. Furthermore, binding was inhibited by heat denaturation and trypsin pretreatment of the plasma membranes [2, 31. All of these observations suggested the presence of a membrane fatty acid 'receptor' protein. This suggestion was pursued by isolation of such a membrane fatty acid binding protein from rat liver plasma membranes. A single step affinity chromatography technique of detergent solubilized plasma membrane proteins over an oleate agarose gel revealed a single protein with a molecular weight of 40 kDa and a pI of 8.5-9.0 [2] (Fig. 1). This membrane fatty acid binding protein (MFABP) had no carbohydrate or lipid components, was poorly soluble in water, showed also affinity for long chain fatty acids in vitro, and was distinct from the 12 kDa cytosolic fatty acid binding protein (cFABP). It was isolated from plasma membranes of rat hepatocytes, cardiomyocytes and jejunal mucosal cells [2, 4, 51. The protein was clearly distinct from rat mitochondria1 glutamic oxaloacetic transaminase (mGOT) [6] which was recently suggested by others to represent the responsible carrier protein [7 ] . This group isolated the protein by a different isolation procedure using