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Signaling Molecules Derived from the Cholesterol Biosynthetic Pathway

1997; Springer Nature; Linguagem: Inglês

10.1007/978-1-4615-5901-6_1

2542-8810

Simon Jackson, Johan Ericsson, Peter A. Edwards,

Natural product bioactivities and synthesis

The isolation and characterization of many of the enzymes involved in the synthesis of cholesterol represented a major tour de force in the 1950s and 1960s (Mead et al., 1986; Porter and Spurgeon, 1981). These early studies led to the realization that the cyclic cholesterol molecule was derived from a polyisoprenoid, which in turn was shown to be composed of repeating five-carbon branched-chain building blocks derived from isopentenyl diphosphate (Rilling, 1985). The condensation of one or more isopentenyl diphosphate molecules with an allylic isoprenoid diphosphate (e.g., dimethylallyl diphosphate, geranyl diphosphate) is catalyzed by a family of related prenyl transferases that differ in their specificity for the allylic substrate (Edwards et al., 1992; Chen et al., 1994). The resulting linear isoprenoids are intermediates in the synthesis of a number of important compounds, including sterols, dolichols, heme a, steroid hormones, 1,25-dihydroxy vitamin D, bile acids, and geranylgeranyl diphosphate (Figure 1). Isoprenoid moieties, such as farnesyl and geranylgeranyl, are also post-translationally attached to certain proteins to produce prenylated proteins (Figure 1). Such modifications affect the localization and functions of the lipidated proteins. Recent studies indicates that isoprenoid alcohols or acids may also functions as novel signaling molecules.