Isoprenoid compounds

There are more than 23 000 known isoprenoid compounds... 

Terpenes are often referred to as isoprenoid compounds and are classified accord mg to the number of isoprene units they contain (Table 26 2)... 

Isoprenoid compounds are biosynthesized from acetate by a process that involves sev eral stages The first stage is the formation of mevalonic acid from three molecules of acetic acid... 

Terpenes and related isoprenoid compounds are biosynthesized from isopentenyl pyrophosphate... 

The isoprenoid compound shown is a scent marker present in the urine of the red fox Sug gest a reasonable synthesis for this substance from 3 methyl 3 buten 1 ol and any necessary organic or inorganic reagents... 

Isonicotinic acid hydrazide reagent 318 Isoprenaiine 395,396 Isoprenoid compounds 44 Isopulegol 59 Isoquercitrin 279, 280, 323 Isoquinoline alkaloids 46, 66, 262 Isorhamnetin 323 Isothiazolones, microbiocidal 45 Isothiocyanates 75 Isotopes, j8-radiation-emitting 41 -, detection limits 41 Itaconic acid 61... 

Squalene is an isoprenoid compound that is found in large quantities in shark liver and in smaller quantities in olives, rice bran and wheat germ. It is a bactericidal compound and an antioxidant and it aids in skin nutrition. Several cosmetic applications of rice bran and rice bran oil arise from the biological effects of their squalene, vitamin E and y-oryzanol content. Since these compounds are fat-soluble, rice bran oil is used for all these preparations. 

Subsequent cyclizations, dehydrogenations, oxidations, etc., lead to the individual naturally occurring carotenoids, but little is known about the biochemistry of the many interesting final structural modifications that give rise to the hundreds of diverse natural carotenoids. The carotenoids are isoprenoid compounds and are biosynthesised by a branch of the great isoprenoid pathway from the basic C5-terpenoid precursor, isopentenyl diphosphate (IPP). The entire biosynthesis takes place in the chloroplasts (in green tissues) or chromoplasts (in yellow to red tissues). 

Spurgeon SL, Porter JW (1981) In biosynthesis of isoprenoid compounds. In Porter JW, Spurgeon SL (eds) John Wiley and Sons, New York, p 1... 

Bark beetles primarily utilize isoprenoid derived pheromones [100,101] and have been the most studied regarding their biosynthesis [8,98]. Earlier work indicated that the isoprenoid pheromones could be produced by the beetle altering host derived isoprenoids however more recent work indicates that for the most part bark beetles are producing pheromones de novo. The production of isoprenoids follows a pathway outlined in Fig. 4 which is similar to the isoprenoid pathway as it occurs in cholesterol synthesis in mammals. Insects cannot synthesize cholesterol but can synthesize farnesyl pyrophosphate. Insects apparently do not have the ability to cyclize the longer chain isoprenoid compounds into steroids. The key enzymes in the early steps of the isoprenoid... 

Carotenoids are isoprenoid compounds that are biosynthesized only by plants and microorganisms. Some carotenoids (a- and p-carotene, p-cryptoxanthine) can be cleaved into vitamin A (retinol) by an enzyme in the small intestine. Carotenoids have been reported to present some effects in the prevention of cardiovascular diseases [410] and in the prevention of some kind of cancers [411]. Furthermore, antioxidant activity has been widely reported [411-414] but a switch to pro-oxidant activity can occur as a function of oxygen concentration [415,416]. 

FIGURE 10-22 Some other biologically active isoprenoid compounds or derivatives. Isoprene structural units are set off by dashed red lines. In most mammalian tissues, ubiquinone (also called coen-... 

The steroid hormones (glucocorticoids, mineralocorticoids, and sex hormones) are produced from cholesterol by alteration of the side chain and introduction of oxygen atoms into the steroid ring system. In addition to cholesterol, a wide variety of isoprenoid compounds are derived from mevalonate through condensations of isopentenyl pyrophosphate and dimethylallyl pyrophosphate. 

Elimination usually involves loss of a proton together with a nucleophilic group such as -OH, -NH3+, phosphate, or pyrophosphate. However, as in Eq. 13-18, step c, electrophilic groups such as -COO-can replace the proton. Another example is the conversion of mevalonic acid-5-pyrophosphate to isopentenyl pyrophosphate (Eq. 13-19) This is a key reaction in the biosynthesis of isoprenoid compounds such as cholesterol and vitamin A (Chapter 22). The phosphate ester formed in step a is a probable intermediate and the reaction probably involves a carbo-cationic intermediate generated by the loss of phosphate prior to the decarboxylation. 

Isoprenoid alcohol phosphokinase 409 Isoprenoid compounds. See also Polyprenyl compounds... 

It is also a precursor for synthesis of polyprenyl (isoprenoid) compounds, and it can give rise to free acetoacetate, an important constituent of blood. Acetoacetate is a (3-oxoacid that can undergo decarboxylation to acetone or can be reduced by an NADH-dependent dehydrogenase to D-3-hydroxybutyrate. Notice that the configuration of this compound is opposite to that of L-3-hydroxybutyryl-CoA which is... 

The second five-carbon branched unit, in which the branch is one carbon further down the chain, is an intermediate in the biosynthesis of polyprenyl (isoprenoid) compounds and steroids. Three two-carbon units are used as the starting material with decarboxylation of one unit. Two acetyl units are first condensed to form acetoacetyl-CoA. Then a third acetyl unit, which has been transferred from acetyl-CoA onto an SH group of the enzyme, is combined with the acetoacetyl-CoA through an ester condensation. The thioester linkage to the enzyme is hydrolyzed to free the product 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). This sequence is illustrated in Eq. 17-5. The thioester group of HMG-CoA is reduced to the... 

Insects communicate through the use of a great variety of volatile pheromones. As mentioned in Chapter 8, Section A,l, some moths utilize acetate esters of various isomers of A7 and A11 unsaturated C14 fatty acids as sex pheromones. Some other moths convert the trans-l 1 -tetradecenyl acetate into the corresponding C14 aldehyde or alcohol, while others use similar compounds of shorter (Cn - C12) chain length.143 Some ants use ketones, such as 4-methyl-3-heptanone, as well as various isoprenoid compounds and pyrazines as volatile signaling compounds.144 Other insects also utilize isoprenoids,145 alkaloids,146 and aromatic substances as pheromones. 

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). 

In animals all isoprenoid compounds are apparently synthesized from mevalonate, which is converted by the consecutive action of two kinases21 23 into mevalonate 5-diphosphate (Fig. 22-1, step b). Mevalonate kinase is found predominantly in peroxisomes, which are also active in other aspects of steroid synthesis in humans.2124 A deficiency of this enzyme is associated with mevalonic aciduria, a serious hereditary disease in which both blood and urine contain very high concentrations of mevalonate.23 Mevalonate diphosphate kinase, which is also a decarboxylase, catalyzes phosphorylation of the 3-OH group of mevalonate (step c, Fig. 22-1) and decarboxylative elimination of phosphate (step d)25 to form isopentenyl diphosphate. 

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