Biosynthesis activated acetate

Fats and fat-like compounds of varying chemical structures are classified as lipids. They have a low molecular weight and are insoluble in water. The original substance in fat biosynthesis is acetyl-CoA (so-called activated acetic acid). On the basis of chemical criteria, they may be divided into simple lipids (glycerides, cholesterol, cholesterol esters, bile acids) and complex lipids, (s. tab. 3.7)... 

Squalene [(a//- )-2,6,10,15,19,23-hexamethyl-2.6, 10,14,18,22-tetracosahexaene]. The most important aliphatic, acyclic triterpene, C30H50, Mr 410.73, mp. -4.8 to -5.2 C, bp. 284-285°C, formula, see steroids. S. was first isolated from fish liver oils and later detected in plant oils and human fat. It is composed of 6 isoprene units and is formed from activated acetate ( acetyl-CoA) via mevalonic acid. It is an intermediate in the biosynthesis of all cyclic triterpenoids and thus also of the steroids. Its enzymatic cyclization to IanosteroI or cycloartenoI requires molecular oxygen and proceeds through (35)-squalene 2,3-epoxide. lit. Annu. Rev. Biochem. 14,555-585 (1982)"Chem. Soc. Rev. 20,129-147 (1991) - Kaiier, No. 34 Nat. Prod. Rep. 2, 525 - 5W (1985) Phytochemisby 27,628 (1988) (biosy nthe-sis) Stryer 1995,692-695.-/HS290/29 CASHI-02-4]... 

Cholesterol biosynthesis is affected by dietary and hormonal factors as well as by various external influences. Cholesterogenesis is enhanced by radiation, thyroid hormones, hypophysectomy, various metal ions and surface active agents. Biosynthesis is inhibited by fasting, thyroidectomy, vanadium salts, and by feeding of cholesterol or some of its steroid precursors. These influences were reviewed by Kritchevsky et al. (1960). In most cases cholesterol synthesis from acetate is more severely inhibited than is synthesis from mevalonate, suggesting that the inhibition occurs at an early step in cholesterol biosynthesis. The inhibition of cholesterol biosynthesis by cholesterol feeding was shown to possess the characteristics of a negative feedback control system (Bucher et al., 1959). 

The cleavage products follow separate pathways of metabolism. Glycerol, closely related to carbohydrates, is either utilized for the biosynthesis of fructose and glucose or, after phosphorylation, is broken down in the same way as the carbohydrates (Chapt. XVIII-1). Fatty acids are decomposed according to the rules of /3-oxidation to C2 units (activated acetate) which may then either be used for biosynthesis or be oxidized to CO2 and H2O through the citrate cycle (Chapt. XI) and the respiratory chain. 

Evidence that acetyl-CoA is the actual active acetate in fungal aromatic biosynthesis was provided by Bassett and Tanenbaum (i960), who showed (a) that coenzyme A could be isolated from the mycelium of P. patulum (b) that radioactive acetyl-CoA, synthesized either from fungal or yeast coenzyme preparations, could be transformed into radioactive patulin by a cell-free extract obtained by the dilute ammonia treatment of mycelial mats. It was also found that biosynthetically-labelled 6-methylsalicylate could be enzymically rearranged to patulin by such extracts. Use of the ammonia extractive procedure followed by partial ammonium sulfate fractionation, gave Lynen and Tada (I96I) an enzyme mixture which synthesized radioactive 6-methylsalicylate from acetyl-1- C-CoA,... 

The second largest class of compounds reported from macroalgae is the polyketides, which comprise approximately a quarter of known algal compounds (Blunt et al. 2007). Polyketides are polymers of acetate (C2) and occasionally propionate (C3) and are very similar to fatty acids in their biosynthetic origin. Polyketides can be found in plants, animals, bacteria, and fungi. With a range of activities as broad as their structures, the polyketides are a diverse family of natural products classified based upon the polyketide synthases (PKSs) responsible for their biosynthesis, primarily type I and type II. 

Ethylphenoxy)triethylamine and 2-(3,4-dimethoxyphenoxy)triethylamine markedly reduce the biosynthesis of limonoids in citrus leaves, presumably by inhibition of cyclase activity. Radio-tracer studies have revealed that limonoids are synthesized in the leaves of citrus and transported to the fruit. The fruit tissue does not appear to be capable of the de novo synthesis of limonoids from acetate or mevalonate. 

Citrus leaves were shown to be the site of limonoic acid A-ring lactone biosynthesis in citrus (55). The lactone accumulated to the level of 2000 ppm in very small leaves but as the leaf grew, the lactone content declined. The lactone content of the fruit increased as the level in the leaves declined. Hasegawa and Hoagland (55) also showed that limonoic acid A-ring lactone was not synthesized in the fruit but in the leaves. The radioactive labeled lactone was isolated from a fruit adjacent to a leaf actively synthesizing it from labeled acetate, indicating that the lactone was synthesized in the leaves and transported to the fruit (55). 

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. 

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