Geranyl acetate pyrophosphate

Introduction of Nitrogen into a Terpenoid Skeleton. The acetate-derived fragments (35) mevalonic acid (30), which yields isopentenyl pyrophosphate (31) and its isomer, 3,3-dimethyl ally pyrophosphate (32) a dimeric C -fragment, geranyl pyrophosphate (33), which gives rise to the iridoid loganin (34) and the trimer famesyl pyrophosphate (35), which is also considered the precursor to C q steroids, have already been mentioned (see Table 3... 

It is well known that the steroid hormones in mammals are biosynthesized from cholesterol. This compound is derived from the acetate-mevalonate pathway through the monoterpene geranyl pyrophosphate, which undergoes several enzymatic reactions to form the triterpene squalene. 

The biosynthesis of monoterpenoids and camphor has been described by several authors (108-llU). Ruzicka (115,116) proposed a unified biogenetic scheme for terpenes. The biosynthetic building blocks for these terpenes are iso-prene units. The biosynthetically active isoprene units are isopentenyl pyrophosphate [l] and dimethyl allyl pyrophosphate [2] the compounds that are derived from acetate via mevalonic acid (Scheme V). Geranyl pyrophosphate [3] is the C-10 precursor for the terpenes (117). Banthorpe and Baxendale (ll8) confirmed the biosynthetic pathway of (iamphor via acetate mevalonate by conducting degradation study of camphor, biosynthesized from l c labelled mevalonic acid. The biosynthesis of camphor is summarised in Scheme VI. 

Manganese acts as a cofactor of mevalonate kinase and farnesyl pyrophosphate synthetase. Mevalonate kinase and possibly one other manganese-activated enzyme are necessary for the formation of mevalonate from acetate (3). Farnesyl pyrophosphate synthetase acts to add one 5-carbon unit to geranyl pyrophosphate to make farnesyl pyrophosphate (4) (Figure 1). 

Steroids are members of a large class of lipid compounds called terpenes. Using acetate as a starting material, a variety of organisms produce terpenes by essentially the same biosynthetic scheme (Fig. 8). The self-condensation of two molecules of acetyl coenzyme A (CoA) forms acetoacetyl CoA. Condensation of acetoacetyl CoA with a third molecule of acetyl CoA, then followed by an NADPH-mediated reduction of the thioester moiety produces mevalonic acid [150-97-0] (72). Phosphorylation of (72) followed by concomitant decarboxylation and dehydration processes produce isopentenyl pyrophosphate. Isopentenyl pyrophosphate isomerase establishes an equilibrium between isopentenyl pyrophosphate and 3,3-dimethylallyl pyrophosphate (73). The head-to-tail addition of these isoprene units forms geranyl pyrophosphate. The addition of another isopentenyl pyrophosphate unit results in the sesquiterpene (C15) famesyl pyrophosphate (74). Both of these head-to-tail additions are catalyzed by prenyl transferase. Squalene synthetase catalyzes the head-to-head addition of two achiral molecules of famesyl pyrophosphate, through a chiral cyclopropane intermediate, to form the achiral triterpene, squalene (75). 

SOLUTION Acetate reacts with ATP to form acetyl adenylate, which then reacts with CoASH to form acetyl-CoA (Section 17.20). Because malonyl-CoA is prepared from acetyl-CoA, the thioester carbonyl carbon of malonyl-CoA will also be labeled. Examining each step of the mechanism for the biosynthesis of isopentenyl pyrophosphate from acetyl-CoA and malonyl-CoA allows you to determine the locations of the radioactively labeled carbons in isopentenyl pyrophosphate. Similarly, the locations of the radioactively labeled carbons in geranyl pyrophosphate can be determined from the mechanism for its biosynthesis from isopentenyl pyrophosphate. And the locations of the radioactively labeled carbons in farnesyl pyrophosphate can be determined from the mechanism for its biosynthesis from geranyl pyrophosphate. Knowing that squalene is obtained from a tail-to-tail linkage of two farnesyl pyrophosphates tells you which carbons in squalene will be labeled. 

Monoterpene biosynthesis has been studied in conifers using labeled precursors such as carbon dioxide, acetate and mevalonate (63,64). Specifically labeled precursors have been employed to deduce mechanistic features of a-plnene (65,66) and 3-carene (67,68) biosynthesis in pine species. Glelzes and co-workers (69) have argued, by way of time-course studies, that the initial formation of acyclic hydrocarbons (oclmene, myrcene) from C02 in Pinus pinaster needles indicated that these olefins serve as precursors to cyclic monoterpenes (a-plnene, 8-pinene) by a reversible protonatlon mechanism. These suggestions, however, are without precedent, and run counter to direct evidence demonstrating that the cyclizatlon of geranyl pyrophosphate occurs without the involvement of free intermediates (17). 

The formation of oxygenated derivatives usually involves oxygenation of the parental hydrocarbons. The essential oil of Artemisia absinthum contains /-sabinyl acetate (42%) (20), geranyl pyrophosphate with a soluble enzyme, is the key cyclic precursor of 3-thujone and other C-3-oxygenated... 

Allylic hydrolysis of geranyl pyrophosphate produces linalool (92). Like geraniol, linalool occurs widely in nature. The richest source is ho leaf, the oil of which can contain well over 90% linalool. Other rich sources include linaloe, rosewood, coriander, freesia, and honeysuckle. Its acetate is also frequently encountered and is a signi cant contributor to the odors of lavender and citrus leaf oils. 

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