Terpenes, isoprenoid activities

The terpenes, carotenoids, steroids, and many other compounds arise in a direct way from the prenyl group of isopentenyl diphosphate (Fig. 22-1).16a Biosynthesis of this five-carbon branched unit from mevalonate has been discussed previously (Chapter 17, Fig. 17-19) and is briefly recapitulated in Fig. 22-1. Distinct isoenzymes of 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) in the liver produce HMG-CoA destined for formation of ketone bodies (Eq. 17-5) or mevalonate.7 8 A similar cytosolic enzyme is active in plants which, collectively, make more than 30,000 different isoprenoid compounds.910 However, many of these are formed by an alternative pathway that does not utilize mevalonate but starts with a thiamin diphosphate-dependent condensation of glyceraldehyde 3-phosphate with pyruvate (Figs. 22-1,22-2). 

A number of compounds important to animal physiology have been identified as isoprenoid compounds. Notable examples are vitamin A, retinal (Section 28-7), and squalene (Table 30-1). Also, terpene hydrocarbons and oxygenated terpenes have been isolated from insects and, like famesol, show hormonal and pheromonal activity. As one example, the juvenile hormone isolated from Cecropia silk moths has the structure shown in 3 ... 

The chemicals that induce hepatic porphyria in man, animals, or chick embryo cells in culture consist of a wide variety of organic compounds that differ in physiologic activity. They include, for example, the central nervous depressants such as the barbiturates, sulfonme-thanes, and glutethimides the anticonvulsant methsuximide the central nervous stimulant bemegride the fungicides griseofulvin and hexachlorobenzene some chlorinated insecticides and the isoprenoid terpenes and steroids [2,10,11,24,25]. 

The basic skeleton of isoprenoids may be modified by the introduction of a wide variety of chemical groups, by isomerization, shift of double bonds, methyl groups, etc. Hence a bewildering number of chemical structures arises. In addition compounds derived from other biogenic pathways may contain isoprene residues. For instance the K vitamins (D 8.1), ubiquinones (D 8.3), chlorophylls (D 10.1), plastoquinones, and tocopherylquinones (D 22.4) have isoprenoid side chains with up to ten isoprene units. Polyketides (D 3.3), alkaloids (D 8.4.2), and coumarins (D 22.2.2) may be substituted by dimethylallyl groups. The terpene residues are attached to nucleophilic sites, such as active methylene groups and phenolic oxygen atoms. 

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