Relationship between fatty acid binding proteins, acetyl-CoA formation and fatty acid synthesis in developing human placenta

Abstract

The relationship between fatty acid binding proteins, ATP citrate lyase activity and fatty acid synthesis in developing human placenta has been studied. Fatty acid binding proteins reverse the inhibitory efect of palmitoyl-CoA and oleate on ATP citrate lyase and fatty acid synthesis. In the absence of these inhibitors fatty acid binding proteins activate ATP citrate lyase and stimulate ( 1- 14 C) acetate incorporation into placental fatty acids indicating binding of endogenous inhibitors by these proteins. Thus these proteins regulate the supply of acetyl-CoA as well as the synthesis of fatty acids from that substrates. As gestation proceeds and more lipids are required by the developing placenta fatty acid binding protein content, activity of ATP citrate lyase and rate of fatty acid synthesis increase indicating a cause and efect relationship between the demand of lipids and supply of precursor fatty acids during human placental development. During embryogenesis when demand of lipid is very high to supply energy and to synthesize cellular membranes for the developing placenta, more lipids and precursor fatty acids are to be synthesized. The rate of fatty acid synthesis and total activities of the synthesizing enzymes are positively correlated in several animal systems. In chicken liver, fatty acid synthesis and the activities of acetyl-CoA carboxylase (Goodridge 1973), malic enzyme and ATP citrate lyase (Goodridge 1968; Silpananta and Goodridge 1971) are correlated when neonatal chicks are fed. Activities of these enzymes are determined largely by the relative concentrations of enzyme activators and inhibitors as well as by the composition of long chain fatty acids and acyl-CoA pool. The long chain fatty acids and their CoA esters may be compartmentalized in the cell and changes in their distribution might affect lipogenesis. It has been suggested that intracellular trafficking of these inhibitors might be affected partly by their binding to fatty acid binding proteins (FABPs) (Spener and Mukherjea 1990). These proteins belong to a class of low molecular mass (14-15 kDa) non-enzymic proteins which bind hydrophobic ligands and are abundantly present in the cytosol of many mammalian cells (Bass 1985; Sweetser et al 1987; Das et al 1989). FABPs are distinct from the recently discovered 10 kDa