Complex lipids, synthesis

Cerebrosides are major constituents of the membrane of brain cells. They are the simplest glycosphingolipids, serving as model substances for more complex lipids of this kind. Furthermore, they are credited with important properties as receptors for hormones and toxins.29 Schemes 4 13 and 4 14 provide a method for preparing sphingosine and its analogs that can be used for the synthesis of cerebroside compounds. 

The first step in the activation of a fatty acid— either for energy-yielding oxidation or for use in the synthesis of more complex lipids—is the formation of its thiol ester (see Fig. 17-5). The direct condensation of a fatty acid with coenzyme A is endergonic, but the formation of fatty acyl-CoA is made exergonic by stepwise removal of two phosphoiyl groups from ATP. First, adenylate (AMP) is transferred from ATP to the carboxyl group of the fatty acid, forming a mixed anhydride... 

In addition to its role as an intermediate in cholesterol biosynthesis, isopentenyl pyrophosphate is the activated precursor of a huge array of biomolecules with diverse biological roles (Fig. 21-48). They include vitamins A, E, and K plant pigments such as carotene and the phytol chain of chlorophyll natural rubber many essential oils (such as the fragrant principles of lemon oil, eucalyptus, and musk) insect juvenile hormone, which controls metamorphosis dolichols, which serve as lipid-soluble carriers in complex polysaccharide synthesis and ubiquinone and plastoquinone, electron carriers in mitochondria and chloroplasts. Collectively, these molecules are called isoprenoids. More than... 

Among the biological lipids, few exceed bovine milk fat in the complexity of fatty acids present and triacylglycerol (TAG) structure. This, together with its importance commercially as a human food, has generated very large data bases on the synthesis and composition of milk fat. In spite of this, Jensen (2002) lamented the paucity of new information on the content of trace fatty acids and complex lipids in milk fat. 

Arachidonic acid, a 20-carbon fatty acid, is the primary precursor of the prostaglandins and related compounds (see Figure 39.3). Arachidonic acid is present as a component of the phospholipids of cell membranes, primarily phosphatidyl inositol and other complex lipids.1 Free arachidonic acid is released from tissue phospholipids by the action of phospholipase A2 and other acyl hydrolases, via a process controlled by hormones and other stimuli (see Figure 39.3). There are two major pathways in the synthesis of the eicosanoids from arachidonic acid (see Figure 39.3). 

Oxidative phosphorylation is central to the metabolism of all higher organisms, because the free energy of hydrolysis of the ATP so generated is used in the synthesis of, inter alia, nucleic acids (Chaps. 7 and 16), proteins (Chaps. 4,9, and 17), and complex lipids (Chap. 6), as well as in processes as diverse as muscle contraction (Chap. 5) and the transmission of nerve impulses. 

Fatty acids are incorporated into complex lipids through de novo synthetic and remodeling pathways. As detailed below and shown in Fig. 2a, intracellular pools of acyl-CoA are involved in processes outside of lipid metabolism and, in many instances, function as important regulatory molecules. Figure 2b illustrates an overview of glycerol phospholipid synthesis and how fatty acids in the form of acyl-CoA enter these metabolic pathways. Readers are referred to the article entitled Lipid Synthesis in this series for specific details regarding these pathways. 

The question then arises by what pathways are archaeal ether lipids biosynthesized and how were these pathways selected rather than those used by all other organisms for acyl ester lipid synthesis The available information on lipid biosynthesis in archaea is based largely, with a few exceptions, on labelling studies with whole cells (see previous reviews [4,5,9,10,13,15,85]). Biosynthetic pathways for archaeol, caldarchaeol and their complex lipid derivatives will now be discussed. 

Archaea are a group of organisms, previously classified as bacteria, from which eubacte-ria and other life may have evolved. A melavonic acid (six carbon)-building block is used for synthesis instead of acetic acid. The generated phytanyl chains are attached to glycerol moieties of complex lipids by ether linkages. Thus, these lipids are unlike anything found in eubacteria or eukaryotes today. 

---