Chapter 21 LIPID BIOSYNTHESIS
Lipids play a variety of cellular roles, some recognized only recently. This chapter describes the biosynthetic pathways for some of the most common cellular lipids, illustrating the strategies employed in assembling these water-insoluble products from water-soluble precursors such as acetate. We first describe the biosynthesis of fatty acids, the primary components of both triacylglycerols and phospholipids, then examine the assembly of fatty acids into triacylglycerols and the simpler membrane phospholipids. Finally, we consider the synthesis of cholesterol, a component of some membranes and the precursor of steroids such as bile acids, sex hormones, and adrenocortical hormones.
Our coverage of lipid biosynthesis is organized around the following principles:
Lipids are the principal form of stored energy in most higher organisms, as well as the major constituents of membranes.
Anabolism is not simply the reverse of catabolism. Biosynthetic pathways typically diverge from breakdown pathways to overcome irreversible steps in catabolism.
Like other anabolic pathways, the reaction sequences in lipid biosynthesis are endergonic and reductive. They use ATP as a source of metabolic energy and a reduced electron carrier (usually NADPH) as a reductant.
Lipid biosynthesis, like other anabolic pathways, is subject to regulation to respond to cellular and organismal requirements. The places where catabolic and anabolic pathways diverge (Principle 2) provide opportunities to impose metabolic regulation to conserve resources and avoid futile cycles.
Like other major classes of biological molecules, lipids have a plethora of cellular functions. Specialized lipids serve as pigments (retinal, carotene), cofactors (vitamin K), detergents (bile salts), transporters (dolichols), hormones (vitamin D derivatives, sex hormones), extracellular and intracellular messengers (eicosanoids, phosphatidylinositol derivatives), and anchors for membrane proteins (covalently attached fatty acids, prenyl groups, phosphatidylinositol). The ability to synthesize a variety of lipids is essential to all organisms.
Lipids are the principal form of stored energy in most higher organisms, as well as the major constituents of membranes.
Anabolism is not simply the reverse of catabolism. Biosynthetic pathways typically diverge from breakdown pathways to overcome irreversible steps in catabolism.
Like other anabolic pathways, the reaction sequences in lipid biosynthesis are endergonic and reductive. They use ATP as a source of metabolic energy and a reduced electron carrier (usually NADPH) as a reductant.
Lipid biosynthesis, like other anabolic pathways, is subject to regulation to respond to cellular and organismal requirements. The places where catabolic and anabolic pathways diverge (Principle 2) provide opportunities to impose metabolic regulation to conserve resources and avoid futile cycles.
Like other major classes of biological molecules, lipids have a plethora of cellular functions. Specialized lipids serve as pigments (retinal, carotene), cofactors (vitamin K), detergents (bile salts), transporters (dolichols), hormones (vitamin D derivatives, sex hormones), extracellular and intracellular messengers (eicosanoids, phosphatidylinositol derivatives), and anchors for membrane proteins (covalently attached fatty acids, prenyl groups, phosphatidylinositol). The ability to synthesize a variety of lipids is essential to all organisms.We will focus on eukaryotes, with occasional digressions to highlight important distinctions in bacteria and plants.