Isoprenoids

D-Mevalonic acid is the fundamental intermediate in the biosynthesis of the terpenoids and steroids, together classed as poly-isoprenoids. The biogenetic isoprene unit is isopentenyl pyrophosphate which arises by enzymic decarboxylation-dehydration of mevalonic acid pyrophosphate. D-Mevalonic acid is almost quantitatively incorporated into cholesterol synthesized by rat liver homogenates. 

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)... 

Although the term terpene once referred only to hydrocarbons current usage includes functionally substituted derivatives as well grouped together under the general term isoprenoids Figure 26 6 (page 1086) presents the structural formulas for a number of representative examples The isoprene units m some of these are relatively easy to identify The three isoprene units m the sesquiterpene farnesol, for example are mdi cated as follows m color They are joined m a head to tail fashion... 

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... 

In keeping with its biogenetic origin m three molecules of acetic acid mevalonic acid has six carbon atoms The conversion of mevalonate to isopentenyl pyrophosphate involves loss of the extra carbon as carbon dioxide First the alcohol hydroxyl groups of mevalonate are converted to phosphate ester functions—they are enzymatically phosphorylated with introduction of a simple phosphate at the tertiary site and a pyrophosphate at the primary site Decarboxylation m concert with loss of the terti ary phosphate introduces a carbon-carbon double bond and gives isopentenyl pyrophos phate the fundamental building block for formation of isoprenoid natural products... 

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... 

Vitamins are classified by their solubiUty characteristics iato fat-soluble and water-soluble groups. The fat-soluble vitamins A, E, and K result from the isoprenoid biosynthetic pathway. Vitamin A is derived by enzymic cleavage of the symmetrical C q beta-carotene, also known as pro-vitamin A. Vitamins E and K result from condensations of phytyldiphosphate (C2q) with aromatic components derived from shikimic acid. Vitamin D results from photochemical ring opening of 7-dehydrocholesterol, itself derived from squalene (C q). 

Amphomycin inhibits bacterial ceU wall synthesis at the translocase step by binding to the large isoprenoid Hpid called undecaprenylphosphate (173,174). In eukaryotes, in a similar manner, amphomycin binds to the large isoprenoid Hpid called doHcholphosphate thus blocking the transfer of mannose from its uridinediphosphate derivative to this Hpid (173—177). Amphomycin has been patented for use as a feed additive (178). 

The organization of Part Two is according to structural type. The first section, Chapter Seven, is concerned with the synthesis of macrocyclic compounds. Syntheses of a number of heterocyclic target structures appear in Chapter Eight. Sesquiterpenoids and polycyclic higher isoprenoids are dealt with in Chapters Nine and Ten, respectively. The remainder of Part Two describes syntheses of prostanoids (Chapter Eleven) and biologically active acyclic polyenes including leukotrienes and other eicosanoids (Chapter Twelve). 

Fluorescein paraffin derivatives, waxes, hydrocarbons [140,141] aliphatic acids [142] hydroquinone and chlorinated derivatives [143] isoprenoids, quinones [111,144] oxathizine fungicides [145] barbiturates, phenothiazines [146]... 

Rhodamine 6G long-chain hydrocarbons [169] squalene, a-amyrin [170] methyl esters of fatty acids [171] glycerides [91] sterols [172, 173] isoprenoids, quinones [HI] lipoproteins [174] glycosphingolipids [175] phenolic lipids [176] phosphonolipids [177] increasing the sensitivity after exposure to iodine vapor [178,179]... 

The final step of the reaction involves the transfer of two electrons from iron-sulfur clusters to coenzyme Q. Coenzyme Q is a mobile electron carrier. Its isoprenoid tail makes it highly hydrophobic, and it diffuses freely in the hydrophobic core of the inner mitochondrial membrane. As a result, it shuttles electrons from Complexes I and II to Complex III. The redox cycle of UQ is shown in Figure 21.5, and the overall scheme is shown schematically in Figure 21.6. 

Qilofophylirt Ithe phytyl isoprenoid group ts-Ol2CiI t. Cfl )jCHjCHMeJ... 

Isoprenoid-substituted flavonoids from Artocarpus (Moraceae) plants 98H(47)1179. 

Identification becomes more difficult in the case of isoparaffins since many structural isomers are possible with increasing carbon number. Nevertheless, all possible isoalkanes from through have been found in crude oils, along with several isomers of and some of Many isoprenoids (e.g., pristane and phytane) which serve as biomarkers to the genesis of petroleum have been detected in significant... 

The antiinflammatory effects of statins likely result from their ability to inhibit the formation of mevalonic acid. Downstream products of this molecule include not only the end product, cholesterol, but also several isoprenoid intermediates that covalently modify ( pre-nylate ) certain key intracellular signaling molecules. Statin treatment reduces leukocyte adhesion, accumulation of macrophages, MMPs, tissue factor, and other proinflammatory mediators. By acting on the MHC class II transactivator (CIITA), statins also interfere with antigen presentation and subsequent T-cell activation. Statin treatment can also limit platelet activation in some assays as well. All these results support the concept that in addition to their favorable effect on the lipid profile, statins can also exert an array of antiinflammatory and immunomodulatory actions. 

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