Cellular uptake of long chain free fatty acids: the structure and function of plasma membrane fatty acid binding protein

Abstract

Publisher Summary Non-esterified long chain fatty acids (LCFA) are important energy substrates, building blocks for the complex lipid components of cellular membranes, and precursors of biological mediators, such as the prostaglandins and leukotrienes. The chapter discusses the mechanisms of cellular uptake of long chain fatty acids. The apparent saturability of LCFA uptake challenged the long-held view that LCFA uptake occurred solely by passive diffusion. Saturability is a necessary, but not sufficient, condition to establish the existence of facilitated transport. The significance of putative LCFA transport systems lies in the roles they play in human physiology, pathophysiology, and disease. The chapter summarizes adipocytes and HepG2 cells that suggests important roles for regulated plasma membrane expression of mAspAT in LCFA transport systems that contribute to the pathogenesis of obesity, type 2 diabetes, and EtOH-associated fatty liver, whereas identification of mAspAT, FAT, and an FATP in particular human placental plasma membranes suggests that they are important for transplacental LCFA transport. Facilitated transport mechanisms increasingly appear to be critical providers of energy substrates to skeletal and cardiac muscle. Finally, a selective LCFA uptake defect is reportedly the basis of a syndrome of recurrent bouts of nonketotic, hypoglycemic acidosis and liver failure requiring transplantation in children. Current work in the field of fatty acids transport provides convincing evidence that cellular LCFA is a regulatable, protein mediated process of considerable, potential clinical importance.