Polyprenol

Abstract: The term isoprenoid is an older term that has been given a renewed use in the last 8 to 10 years to describe a fascinating family of compounds derived from the isoprene building block. Earlier, investigators referred to this family of compounds as terpenes or terpenoids, terms that related to the turpentine oils used in elucidating the chemical structures of isoprenoids in the 1800s. One can also find numerous references to particular classes of isoprenoids such as monoterpenes or sterols, terms referring to investigative approaches that often focused on only a single compound. However, recent results have revealed surprising similarities among branch-point enzymes responsible for directing carbon flow away from the central portion of this biochemical pathway, and others have suggested that understanding the regulation of one branch pathway may involve understanding the coordination and intracellular localization of other portions of the pathway as well. These provocative findings of interrelatedness, which will be discussed more fully below, argue that a more inclusive term such as "isoprenoids" now seems more descriptive of this pathway. Plant isoprenoids comprise a structurally diverse group of compounds that can be divided into classes of primary and secondary metabolites (Fig. 1). Isoprenoids that are primary metabolites include sterols, carotenoids, growth regulators, and the polyprenol substituents of dolichols, quinones, and proteins. These compounds are essential for membrane integrity, photoprotection, orchestration of developmental programs, and anchoring essential biochemical functions to specific membrane systems, respectively. Isoprenoids classified as secondary metabolites include monoterpenes, sesquiterpenes, and diterpenes. Compounds within this latter category are considered secondary because they are not essential for viability. However, they mediate important interactions between plants and their environment. For example, specific terpenoids have been correlated with plant-plant (Stevens, 1984), plantinsect (Gibson and Pickett, 1983), and plant-pathogen (Stoessl et al., 1976) interactions. The isoprenoid biosynthetic pathway is sometimes referred to as the mevalonate pathway in older textbooks. From a technical viewpoint, this makes sense. Mevalonate is a six-carbon intermediate in the pathway, arising from the sequential condensation of three acetyl-CoA units to generate HMG-CoA, which is converted to mevalonate in an irreversible reaction catalyzed by HMG-CoA reductase (HMGR). Due to the irreversible nature of this reaction, early workers correctly surmised that this step was a likely regulatory point of sterol biosynthesis in mammalian systems and eventually correlated the absolute rate of cholesterol biosynthesis with the level of this enzyme activity (Goldstein and Brown, 1990). Whether this enzyme plays a similar rate-limiting role in controlling plant isoprenoid biosynthesis remains unresolved (Bach, 1986; Narita and Gruissem, 1989; Choi et al., 1992). The six-carbon mevalonate is sequentially phosphorylated and decarboxylated to generate IPP, which along with dimethylallyl diphosphate, an interconvertible isomer of IPP, represent the "activated" monomer building blocks for all other isoprenoids. Condensation of dimethylallyl diphosphate with one IPP in a head-to-tail fashion generates GPP; addition of a second IPP unit generates FPP; a third IPP generates GGPP; and so on. These polymerization reactions are catalyzed by prenyltransferases that direct the attack of a carbocation (an electron-deficient carbon atom resulting from the loss of the diphosphate moiety of one substrate) to an electron-rich carbon atom of the double bond on the IPP molecule (Fig. 2). The electrophilic nature of these reactions is unusual relative to the more general nucleophilic condensations occurring in other biosynthetic pathways, but this appears to be a common reaction mechanism among isoprenoid biosynthetic enzymes and especially those catalyzing the cyclization of various isoprenoid intermediates (Gershenzon and Croteau, 1993). The enzymes responsible for the cyclization of GPP, FPP, and GGPP are referred to as monoterpene, sesquiterpene, and diterpene synthases or cyclases and represent reactions committing carbon from the general isoprenoid pathway to end products in 1 Work in the author's laboratory on isoprenoid metabolism is supported by the National Science Foundation. This is journal article 94-3-195 from the Kentucky Agricultural Experiment Station. * E-mail chappell@ukcc.uky.edu; fax 1-606-323-1952. Abbreviations: FPP, farnesyl diphosphate; GGPP, geranylgeranyl diphosphate; GPP, geranyl diphosphate; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; HMGR, HMG-CoA reductase; IPP, isopentenyl diphosphate.