Introduction to Molecular Biology: From Cells to Atoms - Anthony Rees, Michael Sternberg 2002

Carbohydrates and lipids
Lipids: 2

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Fig. 33.1.

NON-GLYCEROL LIPIDS are found in many types of membranes alongside lipids based on a glycerol backbone. They are particularly abundant in nervous tissues, especially the Brain. There are three main classes of non-glycerol lipids: cerebrosides, phosphosphingolipids, and gangliosides. In all of them, Fatty acids and polar groups are linked to a sphingosine molecule.

Sphingosine is an amino alcohol with a long hydrocarbon chain. Structurally, it is very similar to glycerol. Its key features are the presence of a non-hydrolyzable unsaturated hydrocarbon chain attached to one of the three carbon atoms, and an amino group (NH₂) instead of a hydroxyl (OH) group at the central carbon atom.

Ceramide is the primary sphingolipid from which all three classes of non-glycerol lipids are derived. It is formed by attaching a (typically) monoenoic fatty acid to the central amino group of sphingosine via an amide bond (Ch. 6).

Cerebrosides are ceramides to which a monosaccharide, such as galactose, is attached. This forms a glycosidic bond between the C¹ oxygen atom of the sugar (C¹–OH in the β-conformation; Ch. 31) and the carbon atom of the sphingosine CH₂OH group. The fatty acid chain at the central amino group typically contains 22–26 carbon atoms; the example shown in Fig. 33.1 depicts oleic acid, an 18-carbon monoenoic fatty acid. Cerebrosides are found in high concentrations in the brain and mammalian Nervous Tissue. In other tissues, galactose is often replaced by glucose, yielding glucocerebrosides. Cerebrosides are also members of a large group of carbohydrate-containing lipids commonly referred to as Glycolipids.

Phosphosphingolipids are ceramides in which the remaining alcoholic hydroxyl group is esterified with a charged phosphate derivative, such as phosphorylcholine. In this respect, they resemble phosphoglycerides and are similarly amphipathic. The most typical phosphosphingolipid is sphingomyelin, which is a constituent of most membranes and the sole non-glycerol membrane phospholipid.

Gangliosides are ceramides in which the alcohol group is linked via a glycosidic bond to a short, typically branched acidic oligosaccharide. The acidity of this class of glycolipids is due to the presence of neuraminic acid, a monosaccharide that always branches off the main saccharide chain. The Structure of this amino sugar is shown in Fig. 33.2. In human tissues, the amino group is always acetylated (CH₃CO), converting the sugar into N-acetylneuraminic acid (NANA). In animals and plants, the amino group is often replaced by a sugar residue. The linear portion of the saccharide chain typically contains N-acetylgalactosamine (GalNAc), galactose (Gal), and glucose (Glc) linked sequentially. Fig. 33.1 shows ganglioside G_M1, a typical component of brain grey matter. A number of Metabolic Disorders are attributed to defects specifically in ganglioside METABOLISM. The best known is Tay-Sachs disease, in which ganglioside G_M1 accumulates in brain tissue due to a deficiency of the enzyme involved in its breakdown.

Fig. 33.2.

Simple Lipids are lipids that contain no fatty acids. Sometimes called "nonsaponifiable" lipids, they do not yield soap-forming fatty acids upon alkaline Hydrolysis. This group includes Fat-soluble Vitamins, Steroid Hormones, and certain other fat-soluble substances. All simple lipids are based on Steroids and Terpenes.

Steroids are derivatives of a saturated polycyclic hydrocarbon (consisting of multiple fused rings). They occur in both plants and animal tissues and perform a variety of Functions, ranging from Sex Hormones in animals to vitamin precursors in plants. The most common animal steroid is Cholesterol, whose structural formula is shown in Fig. 33.3.

Fig. 33.3.

Cholesterol is the precursor to all animal steroid hormones (such as the male sex hormone testosterone or the female sex hormone estrogen). It is also a major component of Bile acids, which, upon secretion by the Liver into the Small Intestine, react with dietary fatty acids and acylglycerols to facilitate their absorption. Although perhaps less obvious, cholesterol is also a mildly amphipathic lipid whose size and properties make it a suitable membrane component in many animal Cells (constituting 40 to 60% of total lipids in mammalian erythrocytes). The rigidity of the cholesterol polycyclic ring confers specific properties on the membranes in which it resides (Ch. 34). Cholesterol is rarely found in plant cells.

Terpenes are simple steroids whose structural foundation is the five-carbon hydrocarbon isoprene (Fig. 33.4). Molecules of this hydrocarbon assemble into diverse linear or cyclic structures, giving rise to numerous substances such as plant "fragrant" oils with characteristic aromas (for example, menthol is a terpene oil extracted from mint).

Fig. 33.4.

Vitamins are small organic molecules that exhibit high biological activity even at very low concentrations. They are classified into fat-soluble (vitamins A, D, E, and K) and Water-soluble [all B-group vitamins, vitamins C, H (biotin), and P] vitamins. Here, only fat-soluble vitamins are of interest to us because their ability to dissolve in fats implies a certain chemical similarity to lipids. Vitamin A, which plays a crucial role in Vision, consists of a hydrocarbon ring with attached polar groups and a long terpene side chain. Vitamin D, essential for Calcium and phosphorus metabolism, resembles a partially opened cholesterol molecule. Vitamin E, which functions partly as an antioxidant, consists of two fused hydrocarbon rings with a long branched hydrocarbon side chain. Vitamin K, the last in this group, is required for Blood clotting; structurally, it resembles vitamin E, but one of its rings is a quinone, and its side chain has a slightly different architecture.