Polyisoprenoid synthesis and metabolism.

Polyisoprenoids or polyprenyls are lipids formed by the sequential condensation of the Ci unit of isopentenyl (3-methylbut-3-enyl) diphosphate with its allylic isomeric form, 3,3-dimethylallyl diphosphate and with further allylic diphosphates resulting from such condensation. The polyprenyl diphosphates function as donors or intermediates in the synthesis of numerous products which include sterols, dolichol, coenzyme Q. haem a, certain tRNAs, and prenylated proteins (reviewed in [ 1, 21). Important products specific to plants include carotenoids, prenylquinones, chlorophylls and cytokinins [ 31. The regulation of isoprenoid synthesis and metabolism is best understood in the context of cholesterol synthesis. A large number of studies have demonstrated that the key regulatory enzyme in this pathway is hydroxymethylglutaryl-CoA (HMGCoA) reductase (reviewed in [4, 51). This enzyme is controlled at the level of transcription, translation, protein stability, phosphorylation and thiol status of the cell, making it one of the most highly regulated enzymes of nature [4, 51. Other enzymes of cholesterol synthesis are coordinately regulated with HMG-CoA reductase (EC 1.1.1.34); these include HMG-CoA synthase (EC 4.1.3.5) [6, 71, mevalonate kinase (EC 2.7.1.36) [8], and farnesyl diphosphate (FPP) synthetase (EC 2.5.1.10) [9]. FPP synthetase catalyses the 1’-4 condensation of two molecules of isopentenyl diphosphate with dimethylallyl diphosphate to form the C, FPP [lo]. Thus this enzyme synthesizes a key iso-