The Biosynthesis of Membrane Lipids and Steroids

When you have mastered this chapter, you should be able to complete the following objectives. 

Name the three major lipid-based components of biological membranes (Chapter f2). 

Phosphatidate Is a Common Intermediate in the Synthesis of Phospholipids and Triacylglycerols (Text Section 26.1) 

Describe the roles of phosphatidate, glycerol 3-phosphate, lysophosphatidate, and diacylglycerol (DAG) in the synthesis of triacylglycerols and phospholipids. 

List the primary biological functions of triacylglycerols and phospholipids. 

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Sterols and Cholesterol. Natural sterols are crystalline C76 C1(1 steroid alcohols containing an aliphatic side chain at C17. Sterols were first isolated as lionsaponifiable fractions of lipids from various plant and animal sources and have been identified in almost all types of living organisms. By far, the most common sterol in vertebrates is cholesterol (8). Cholesterol serves two principal functions in mammals. First, cholesterol plays a role in the structure and function of biological membranes.. Secondly, cholesterol serves as a central intermediate in the biosynthesis of many biologically active steroids, including bile acids, corticosteroids, and sex hormones. 

Various inborn errors of metabolism (Table 25-1) result from deficiencies or absence of some of the enzymes listed in Figure 25-9. Some of these are discussed later in the chapter. The relationship of carbohydrate metabolism to the production of lactate, ketone bodies, and triglycerides is also depicted in Figure 25-9. The pentose phosphate pathway, also known as the hexose monophosphate shunt, is an alternative pathway for glucose metaboUsm that generates the reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH), which is used in maintaining the integrity of red blood cell membranes, in lipid and steroid biosynthesis, in hydroxylation reactions, and in other anabolic reactions. The complete picture of intermediary metabolism of carbohydrates is rather complex and interwoven with the metabolism of lipids and amino acids. For details, readers should consult a biochemistry textbook. 

The ultimate precursor of all the carbon atoms in cholesterol and in the other steroids that are derived from cholesterol is the acetyl group of acetyl-GoA. There are many steps in the biosynthesis of steroids. The condensation of three acetyl groups produces mevalonate, which contains six carbons. Decarboxylation of mevalonate produces the five-carbon isoprene unit frequently encountered in the structure of lipids. The involvement of isoprene imits is a key point in the biosynthesis of steroids and of many other compounds that have the generic name terpenes. Vitamins A, E, and K come from reactions involving terpenes that humans cannot carry out. That is why we must consume these vitamins in our diets vitamin D, the remaining lipid-soluble vitamin, is derived from cholesterol (Section 8.8). Isoprene units are involved in the biosynthesis of ubiquinone (coenzyme Q) and of derivatives of proteins and tRNA with specific five-carbon units attached. Isoprene units are often added to proteins to act as anchors when the protein is attached to a membrane. 

Cholesterol is a major constituent of the cell membranes of animal cells (see p. 216). It would be possible for the body to provide its full daily cholesterol requirement (ca. 1 g) by synthesizing it itself However, with a mixed diet, only about half of the cholesterol is derived from endogenous biosynthesis, which takes place in the intestine and skin, and mainly in the liver (about 50%). The rest is taken up from food. Most of the cholesterol is incorporated into the lipid layer of plasma membranes, or converted into bile acids (see p. 314). A very small amount of cholesterol is used for biosynthesis of the steroid hormones (see p. 376). In addition, up to 1 g cholesterol per day is released into the bile and thus excreted. 

Metabolism employs phosphorus compounds in many ways. Phosphate esters are central to information storage, serve as the currency for energy exchange, and contribute to membrane fluidity. They are important intermediates in carbohydrate metabolism, in formation of nucleotides and their assembly into RNA and DNA, and in steroid fabrication and protein lipidation through the isoprenoid biosynthesis pathways. They hold key roles in cell signaling processes, including G-protein... 

Membrane-located enzymes in the sER catalyze lipid synthesis. Phospholipid synthesis (see p. 170) is located in the sER, for example, and several steps in cholesterol biosynthesis (see p. 172) also take place there. In endocrine cells that form steroid hormones, a large proportion of the reaction steps involved also take place in the sER (see p. 376). 

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