Glycerophospholipids in brain: their metabolism, incorporation into membranes, functions, and involvement in neurological disorders

Abstract

Neural membranes contain several classes of glycerophospholipids which turnover at different rates with respect to their structure and localization in different cells and membranes. The glycerophospholipid composition of neural membranes greatly alters their functional efficacy. The length of glycerophospholipid acyl chain and the degree of saturation are important determinants of many membrane characteristics including the formation of lateral domains that are rich in polyunsaturated fatty acids. Receptor-mediated degradation of glycerophospholipids by phospholipases A_l, A₂, C, and D results in generation of second messengers such as arachidonic acid, eicosanoids, platelet activating factor and diacylglycerol. Thus, neural membrane phospholipids are a reservoir for second messengers. They are also involved in apoptosis, modulation of activities of transporters, and membrane-bound enzymes. Marked alterations in neural membrane glycerophospholipid composition have been reported to occur in neurological disorders. These alterations result in changes in membrane fluidity and permeability. These processes along with the accumulation of lipid peroxides and compromised energy metabolism may be responsible for the neurodegeneration observed in neurological disorders.

Introduction

Brain tissue contains relatively high amounts of glycerophospholipids. In adult brain, they account for ≈20–25% of the dry weight. In neural membranes, the glycerophospholipids, along with cholesterol and glycolipids, represent ≈50–60% of the total membrane mass with proteins accounting for most of the remainder. Glycerophospholipids are amphipathic molecules. They contain polar and nonpolar ends. The polar end is called the head group and the nonpolar end is referred to as the tail. The polar end is charged due to the ionization of the phosphate group and nitrogenous base. The nonpolar tail groups (fatty acid acyl chains) are hydrophobic and tend to aggregate in an aqueous environment. Variations in the head group, length of the phospholipid acyl chains and the degree of saturation produce changes in surface charge and physicochemical characteristics of neural membranes. Among the membranes of the brain, myelin contains the highest content of glycerophospholipids. The major glycerophospholipids include ethanolamine plasmalogen and phosphatidylcholine. The phospholipid composition of myelin is similar to that of white matter and very different from that of gray matter.

Four major classes of glycerophospholipids are found in neural membranes. The first three classes, 1,2-diacyl glycerophospholipid, 1-alk-1′-enyl-2-acyl glycerophospholipid or plasmalogen, and 1-alkyl-2-acyl glycerophospholipid, have a glycerol backbone with a fatty acid, usually unsaturated, at carbon-2 and a phosphobase (choline, ethanolarnine, serine or inositol) at carbon-3 of the glycerol moiety. The fourth class, of which the only representative is sphingomyelin, contains ceramide linked to phosphocholine through its primary hydroxyl group. These glycerophospholipids provide neural membranes with stability, fluidity, and permeability. They are also required for the proper function of integral membrane proteins, receptors, and ion-channels (Farooqui and Horrocks, 1985). The purpose of this review is to discuss the progress that has been made recently on neural membrane glycerophospholipid metabolism. This includes their incorporation in the membrane for their role as a storage depot for second messengers, in apoptosis, and in modulating the activities of transporters, membrane-bound enzymes, and ion-channels.