Saturated acids biosynthesis

The next three steps—reduction of the /3-carbonyl group to form a /3-alcohol, followed by dehydration and reduction to saturate the chain (Figure 25.7) — look very similar to the fatty acid degradation pathway in reverse. However, there are two crucial differences between fatty acid biosynthesis and fatty acid oxidation (besides the fact that different enzymes are involved) First, the alcohol formed in the first step has the D configuration rather than the L form seen in catabolism, and, second, the reducing coenzyme is NADPH, although NAD and FAD are the oxidants in the catabolic pathway. 

Cells regulate the lipid compositions of their plasma membrane so that a reasonable membrane fluidity is main-tained. They do this by controlling fatty acid biosynthesis so as to vary the lengths of the fatty acid chains and the ratio of unsaturated to saturated fatty acids (see chapter 19). If cells are grown at low temperatures, their phospholipids contain more unsaturated fatty acids or fatty acids with shorter chains or both. These adjustments shift the Tm to lower temperatures, with the result that (to the extent that the melting transition is sharp enough to be measureable) the Tm re-... 

Mutations in desatl affect HC, resulting in a very large decrease in 7-HC in males, and in 7- and 7,11-HC in females, with a parallel increase in saturated HC synthesis (Labeur el al., 2002 Ueyama el al., 2005 Marcillac et al., 2005a,b). Lipid metabolism is impaired too, with both quantitatively and qualitatively altered fatty acid biosynthesis the overall quantity of fatty acids was shown to be reduced by half and that of vaccenic acid, the common precursor to 7-HC in both sexes, reduced by a factor of six in a desatl mutant (Ueyama et al., 2005). 

Elongation by two carbon atoms occurs commonly in fatty acid biosynthesis. It is a variant of de novo chain-lengthening and occurs with acetyl or malonyl CoA or ACP derivatives. The substrate is any preformed saturated or unsaturated acid. For example, erucic (22 1) in high-emcic acid rapeseed oil and nervonic acid (24 1) in seed oil are formed from oleic acid by two and three elongations, respectively ... 

A-ACPs in higher plants are homodimeric soluble proteins of about 70 kDa. They catalyze the first and most important desaturation of stearoyl-acyl carrier protein, resulting in an oleoyl-acyl carrier protein, which is a major precursor in fatty acid biosynthesis in plants. A-ACP is involved in controlling the ratio of saturated to unsaturated... 

Fatty acids have predominantly even numbers of carbon atoms because they are effectively formed from acetyl (C2) units, which are derived from glucose in the presence of various enzymes, coenzymes and carrier proteins. An overall scheme for saturated fatty acid biosynthesis is presented in Fig. 2.13, in which it can be seen that the first step is the formation of acetyl coenzyme A (often abbreviated to acetyl-CoA). One molecule ofacetyl-CoA undergoes addition of CO, to form malonyl-CoA, while the acetyl group on another molecule is transferred to an enzyme (fatty acid synthase). The malonyl unit (C3) is added to the enzyme-bound acetyl unit, which produces a butyryl group following loss of C02, dehydration and reduction. Six further steps of combined malonyl addition, decarboxylation, dehydration and reduction occur to yield palmitate (C16). Higher acids are built from palmitate in a similar... 

Hoshita et al. have shown that liver microsomes from the green iguana, in which the major biliary bile salt is tauroallocholate, convert 7a,12a-dihydroxycholest-4-en-3-one (XVII) into 5a-cholestane-3a,7a,12a-triol (XVIII) rather than into 5)8-choles-tane-3 ,7a,12a-triol (VIII) which is involved in cholic acid biosynthesis [164]. On the basis of this result and that obtained from studies with carp liver [151], it can be assumed that 5a-bile acids and alcohols are formed from cholesterol by a modification of the biosynthetic pathway to the corresponding 5y8 isomers in which the only difference is the stereospedfic saturation of the A double bond of the intermediate XVII. 

See also Acetyl-CoA, Fats, Albumin, Fatty Acid Activation, Oxidation of Saturated Fatty Acids, Oxidation of Unsaturated Fatty Acids, Fatty Acid Biosynthesis Strategy, Palmitate Synthesis from Acetyl-CoA, Fatty Acid Desaturation, Essential Fatty Acids, Control of Fatty Acid Synthesis, Molecular Structures and Properties of Lipids (from Chapter 10)... 

Isoniazid is bacteriostatic for resting bacilli but bactericidal for dividing microorganisms. Isoniazid is a prodrug that is converted by mycobacterial catalase-peroxidase into an active metabolite. It inhibits biosynthesis of my colic acids—long, branched lipids that are attached to a unique polysaccharide in the mycobacterial cell wall. Mycolic acids are unique to mycobacteria. The target of the isoniazid derivative is enoyl-ACP reductase of fatty acid synthase II, which converts unsaturated to saturated fatty acids in mycolic acid biosynthesis. 

Although the number of fatty acids detected in plant tissues approaches 300, most of them only occur in a few plant species (Hitchcock and Nichols, 1971). The major fatty acids are all saturated or unsaturated monocarboxylic acids with an unbranched even-numbered carbon chain. The saturated fatty acids, lauric (dodecanoic), myristic (tetradecanoic), palmitic (hexadeca-noic), and stearic (octadecanoic), and the unsaturated fatty acids, oleic (cis-9-octadecenoic), linoleic (c/5 -9,cw-12-octadecadienoic), and linolenic (all-cij-9,12,15-octadecatrienoic (Table I), together account for almost all of the fatty acid content of higher plants. For example, about 94% of the total fatty acids of commercial oils and 89-97% of leaf fatty acids consist of these seven structures alone. It will be noted that the unsaturated acids all contain a cis-9 double bond and that the polyunsaturated acids contain a methylene-interrupted structure. The four saturated fatty acids differ from each other by two carbons. These structural relationships are due to the principal pathways of fatty acid biosynthesis in plants (see Stumpf, this volume. Chapter 7). 

Volpe JJ, Vagelos PR. Saturated faity acids. Biosynthesis and its regulation. Annu Rev Biochem 1973 42 21-60. 

The basic pathways for fatty acid biosynthesis and palmitic acid biosynthesis have already been discussed. But the biosynthesis of fatty acid in brain raises special problems, especially with respect to the biosynthesis of long-chain, even- and odd-numbered saturated or unsaturated fatty acids. 

Most of the compounds among the unsaturated sesquiterpenoid derivatives investigated as inhibitors of cholesterol biosynthesis can be classified as farnesinic acid analogs. Farnesinic acid itself (CXXXVIII) has been found to inhibit incorporation of mevalonic acid into cholesterol when tested in rat liver homogenates [329]. Catal3d ic reduction of farnesinic acid furnished the saturated acid... 

SATURATED AND MONO-UN SATURATED FATTY ACID BIOSYNTHESIS IN BRAIN RELATION TO DEVELOPMENT IN NORMAL AND DYSMYELINATING MUTANT MICE... 

Birge, C.H., Silbert, D.F. and Vagelos, P.R. (1967) A p-hydroxydecanoyl-ACP dehydrase speeifie for saturated fatty acid biosynthesis in. coli. Biochem. Biophys. Res. Commun. 29 808-814. 

Figure 16.4 Long-chain and very long-chain fatty acid biosynthesis in mammals. The long-chain saturated fatty acids and unsaturated fatty acids of the n-10, n-7, and n-9 families (Top panel) can be synthesized from palmitic acid (Cl6 0) produced by the cellular fatty acid synthesis machinery. Long-chain fatty acids of the n-6 and n-3 famihes can only be synthesized from their respective precursors obtained from diets. The symbols of, , and stand for the involved activities of desaturation, elongation, and peroxisomal 3-oxidation, respectively, in the steps. Many isoforms of the genes corresponding to these activities were identified (see the review [34] for details).

Higher saturated ahphatic dicarboxyhc acids, such as malonic, succinic and glutaric acids and other higher homologues of oxahc acid, are found in many food raw materials and foods, but usuahy in smaher quantities. They are mainly intermediates of fatty acids biosynthesis, the citric acid cycle and other metabohc processes, but only succinic acid occurs in a somewhat larger amount in some fruits (e.g. in currants and strawberries). Ah the above mentioned dicarboxyhc acids, including oxahc, adipic, pimehc, suberic acids... 

The skeletons of pyrrolizidine alkaloids are derived from 2,3,5,6,7,8-hexahydro-lH-pyrrolizine, known as pyrrolizidine (10-11), and from pyrrolizidine-M-oxide (10-12). The bases of the pyrrolizidine alkaloids are necines (necine bases) derived from bicyclic amino alcohols, which have their origin in 1-hydroxymethylpyrrolizidine. Necines may be saturated or may have a double bond at C-1 of ring B and may also have an additional one or two hydroxyl groups at C-2, C-6 or C-7. Necines are esterified with carboxylic acids, which are called neck acids. Biosynthesis takes place in the roots, where the alkaloids occur as the corresponding JV-oxides. They are then transported to the aerial parts of the plant and stored in vacuoles. 

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