Phospholipids are polar, ionic compounds that consist of an alcohol (such as choline or ethanolamine) linked to diacylglycerol (DAG) through a phosphodiester bond. This bond produces phosphatidylcholine or phosphatidylethanolamine. Alternatively, the alcohol sphingosine can be attached to a long-chain fatty acid to form ceramide. By adding phosphorylcholine, sphingomyelin is created. Phospholipids are the primary lipids found in cell membranes. They also serve as components of lung surfactant and bile. Dipalmitoylphosphatidylcholine, also known as dipalmitoyl lecithin, is the main lipid component of lung surfactant. Insufficient production of surfactant leads to respiratory distress syndrome. Phosphatidylinositol (PI) acts as a reservoir for arachidonic acid in membranes. The phosphorylation of PI within the membrane produces phosphatidylinositol 4,5-bisphosphate (PIP2). Phospholipase C degrades PIP2 in response to the binding of various neurotransmitters, hormones, and growth factors to membrane G protein-coupled receptors. The resulting degradation products, inositol 1,4,5-trisphosphate (IP3) and DAG, facilitate the mobilization of intracellular calcium and the activation of protein kinase C. These processes work together to elicit cellular responses. Specific proteins can be covalently attached to membrane-bound PI through a carbohydrate bridge, forming a glycosyl phosphatidylinositol (GPI) anchor. A deficiency in GPI synthesis in hematopoietic cells leads to the hemolytic disease paroxysmal nocturnal hemoglobinuria. Phosphoglyceride degradation is carried out by phospholipases present in all tissues and pancreatic juice. Sphingomyelin is broken down into ceramide and phosphorylcholine by the lysosomal enzyme sphingomyelinase. A deficiency of this enzyme causes Niemann-Pick (A and B) disease. Glycosphingolipids are ceramide derivatives with attached carbohydrates. The addition of a single sugar molecule results in a cerebroside, while an oligosaccharide produces a globoside, and the addition of an acidic N-acetylneuraminic acid molecule produces a ganglioside. Glycosphingolipids are mainly found in cell membranes of the brain and peripheral nervous tissue, with high concentrations in the myelin sheath. They are antigenic. Glycolipids are degraded in the lysosomes by acid hydrolases. A deficiency in any of these enzymes causes a sphingolipidosis, characterized by the accumulation of a specific sphingolipid. Prostaglandins (PG), thromboxanes (TX), and leukotrienes (LT), collectively known as eicosanoids, are produced in small quantities in almost all tissues. They act locally and have a short half-life. These molecules function as mediators of the inflammatory response. Arachidonic acid, derived from the essential fatty acid linoleic acid through elongation and desaturation, serves as the immediate precursor of the primary class of human PG (those with two double bonds). It is stored in the membrane as part of a phospholipid, typically PI. Arachidonic acid is released from the phospholipid by phospholipase A2, which is inhibited by cortisol. The synthesis of PG and TX begins with the oxidative cyclization of free arachidonic acid, resulting in PGH2, catalyzed by PGH2 synthase (also known as prostaglandin endoperoxide synthase). This endoplasmic reticular membrane protein possesses two catalytic activities: fatty acid cyclooxygenase (COX) and peroxidase. There are two isozymes of PGH2 synthase: COX-1 (constitutive) and COX-2 (inducible). Aspirin irreversibly inhibits both isozymes.
Phospholipids are polar, ionic compounds composed of an alcohol (for example, choline or ethanolamine) attached by a phosphodiester bond either to diacylglycerol (DAG), producing phosphatidylcholine or phosphatidylethanolamine, or to the amino alcohol sphingosine (Fig. 17.25). Addition of a long-chain fatty acid to sphingosine produces a ceramide. Addition of phosphorylcholine produces the phospholipid sphingomyelin. Phospholipids are the predominant lipids of cell membranes. Nonmembrane phospholipids serve as components of lung surfactant and bile. Dipalmitoylphosphatidylcholine, also called dipalmitoyl lecithin, is the major lipid component of lung surfactant. Insufficient surfactant production causes respiratory distress syndrome. Phosphatidylinositol (PI) serves as a reservoir for arachidonic acid in membranes. The phosphorylation of membrane-bound PI produces phosphatidylinositol 4,5-bisphosphate (PIP2). This compound is degraded by phospholipase C in response to the binding of various neurotransmitters, hormones, and growth factors to membrane G protein– coupled receptors. The products of this degradation, inositol 1,4,5trisphosphate (IP3) and DAG, mediate the mobilization of intracellular calcium and the activation of protein kinase C, which act synergistically to evoke cellular responses. Specific proteins can be covalently attached via a carbohydrate bridge to membrane-bound PI, forming a glycosyl phosphatidylinositol (GPI) anchor. A deficiency in GPI synthesis in hematopoietic cells results in the hemolytic disease paroxysmal nocturnal hemoglobinuria. The degradation of phosphoglycerides is performed by phospholipases found in all tissues and pancreatic juice. Sphingomyelin is degraded to a ceramide plus phosphorylcholine by the lysosomal enzyme sphingomyelinase, a deficiency of which causes Niemann-Pick (A and B) disease. Glycosphingolipids are derivatives of ceramides to which carbohydrates have been attached. Adding one sugar molecule to the ceramide produces a cerebroside, adding an oligosaccharide produces a globoside, and adding an acidic N-acetylneuraminic acid molecule produces a ganglioside. Glycosphingolipids are found predominantly in cell membranes of the brain and peripheral nervous tissue, with high concentrations in the myelin sheath. They are antigenic. Glycolipids are degraded in the lysosomes by acid hydrolases. A deficiency of any one of these enzymes causes a sphingolipidosis, in which a characteristic sphingolipid accumulates. Prostaglandins (PG), thromboxanes (TX), and leukotrienes (LT), the eicosanoids, are produced in very small amounts in almost all tissues, act locally, and have an extremely short half-life. They serve as mediators of the inflammatory response. Arachidonic acid is the immediate precursor of the predominant class of human PG (those with two double bonds). It is derived by the elongation and desaturation of the essential fatty acid linoleic acid and is stored in the membrane as a component of a phospholipid, generally PI. Arachidonic acid is released from the phospholipid by phospholipase A2 (inhibited by cortisol). Synthesis of the PG and TX begins with the oxidative cyclization of free arachidonic acid to yield PGH2 by PGH2 synthase (or, prostaglandin endoperoxide synthase), an endoplasmic reticular membrane protein that has two catalytic activities: fatty acid cyclooxygenase (COX) and peroxidase. There are two isozymes of PGH2 synthase: COX-1 (constitutive) and COX-2 (inducible). Aspirin irreversibly inhibits both.