Chain elongation pathway

Other enzymes in the aconitase family include isopropylmalate isomerase and homoaconitase enzymes functioning in the chain elongation pathways to leucine and lysine, both of which are pictured in Fig. 17-18.90 There are also iron-sulfur dehydratases, some of which may function by a mechanism similar to that of aconitase. Among these are the two fumarate hydratases, fumarases A and B, which are formed in place of fumarase C by cells of E. coli growing anaerobically.9192 Also related may be bacterial L-serine and L-threonine dehydratases. These function without the coenzyme pyridoxal phosphate (Chapter 14) but contain iron-sulfur centers.93-95 A lactyl-CoA... 

Kroymann, J., Textor, S., Tokuhisa, J.G., Falk K.L., Bartram, S., Gershenzon, J. and Mitchell-Olds, Z. (2001) A gene controlling variation in Arabidopsis glucosinolate composition is part of the methionine chain elongation pathway. Plant Phi/sioL, 127, 1077-88. 

The aim of this chapter was to provide evidence that p-oxidation and carbon recycling compete sufficiently effectively with the desaturation-chain elongation pathway for dietary a-linolenate that, in some circumstances, conversion of a-linolenate to docosahexaenoate is... 

Figure 2.5 Condensation Reactions of the Chain Elongation Pathway for the Shortest and Longest 2-Oxo Acid Derivatives of Methionine in Arabidopds.

GRASER, G., SCHNEIDER, B., OLDHAM, N.J., GERSHENZON, J., The methionine chain elongation pathway in the biosynthesis of glucosinolates in Eruca. saliva (Brassicaceae)., Xrc/i. Biochem. Biophys., 2000,378, 411-419. 

Biosynthesis of MCL-PHAs involves three different pathways namely (1) de novo fatty acid biosynthesis, (2) P-oxidation pathway and (3) chain elongation pathway, which is elucidated in Fig. 8.4. 

Chain elongation pathway is another route via which MCL-PHA precursors can be generated from non-related carbon sources by extending the acetyl CoA to acyl CoA. MCL-PHA precursors generated by the elongation of acyl CoA derived from fatty acids in this pathway is significant however, it only forms a minute fraction of the pathway used for the total PHA accumulation within the bacteria. The final step which involves the polymerisation of the (/J)-3-hydroxyacyl CoA into poly-(ff)-3-hydroxyacyl CoA is catalysed by the PHA synthase enzyme with the concomitant release of CoA (Zinn et al., 2001). 

Rates of Component Reactions in the Microsomal Chain Elongation Pathway ... 

Fig. 1. The biosynthetic pathvay of the major fatty acids in edible vegetable oilseeds. The chain elongation pathway from oleic to eruclc acid is unique to the Brassica oil crops.

Historically, many attempts have been made to systematize the arrangement of fatty acids in the glyceride molecule. The even (34), random (35), restricted random (36), and 1,3-random (37) hypotheses were developed to explain the methods nature utilized to arrange fatty acids in fats. Invariably, exceptions to these theories were encountered. Plants and animals were found to biosynthesize fats and oils very differently. This realization has led to closer examination of biosynthetic pathways, such as chain elongation and desaturation, in individual genera and species. 

Fig. 3 Proposed biosynthetic pathways for the production of the sex pheromone components in the indicated insects. Common mechanisms include fatty acid synthesis, desaturation, chain elongation, and decarboxylation...

P. putida grown with hexanoic acid contained approximately 75, 11, and 10 mol% of 3HHx,3HO, and 3HD units and also small amounts of four unsaturated repeating units. The mechanism for the formation of 3HO unit was investigated by 13C NMR study, which showed that the most of 3HO units found in this PHA were formed by the reaction of hexanoic acid with acetyl-CoA [53]. These results confirmed that P. putida produces 3HA units by fatty acid synthesis pathway, through a -oxidation and chain elongation process. 

FIGURE 3-7 Pathways for the interconversion of brain fatty acids. Palmitic acid (16 0) is the main end product of brain fatty acid synthesis. It may then be elongated, desaturated, and/or P-oxidized to form different long chain fatty acids. The monoenes (18 1 A7, 18 1 A9, 24 1 A15) are the main unsaturated fatty acids formed de novo by A9 desaturation and chain elongation. As shown, the very long chain fatty acids are a-oxidized to form a-hydroxy and odd numbered fatty acids. The polyunsaturated fatty acids are formed mainly from exogenous dietary fatty acids, such as linoleic (18 2, n-6) and a-linoleic (18 2, n-3) acids by chain elongation and desaturation at A5 and A6, as shown. A A4 desaturase has also been proposed, but its existence has been questioned. Instead, it has been shown that unsaturation at the A4 position is effected by retroconversion i.e. A6 unsaturation in the endoplasmic reticulum, followed by one cycle of P-oxidation (-C2) in peroxisomes [11], This is illustrated in the biosynthesis of DHA (22 6, n-3) above. In severe essential fatty acid deficiency, the abnormal polyenes, such as 20 3, n-9 are also synthesized de novo to substitute for the normal polyunsaturated acids. 

The fatty acid synthesis pathway can be seen to occur in two parts. An initial priming stage in which acetyl-CoA is converted to malonyl-CoA by a carboxylation reaction (Figure 6.9) is followed by a series of reactions which occur on a multi-enzyme complex (MEC), which achieves chain elongation forming C16 palmitoyl-CoA. The whole process occurs in the cytosol. 

Figure 7 The direct and indirect pathways of tRNA asparaginylation. The direct pathway consists of charging by AsnRS on tRNA " of free Asn formed with asparagine synthetase A or B. The Asn-tRNA " binds the EF-Tu factor in bacteria (or EF-1A in eukaryotes and archaea) to be carried to the ribosome, in the indirect pathway, a nondiscriminating AspRS (ND-AspRS) charges Asp on tRNA " Asp-tRNA " does not bind the eiongation factor but is converted by the tRNA-dependent trimeric amidotransferase GatCAB into Asn-tRNA ", which binds the EF-Tu factor and is carried to the ribosome where it is used for polypeptide chain elongation.

Because carbohydrates are so frequently used as substrates in kinetic studies of enzymes and metabolic pathways, we refer the reader to the following topics in Ro-byt s excellent account of chemical reactions used to modify carbohydrates formation of carbohydrate esters, pp. 77-81 sulfonic acid esters, pp. 81-83 ethers [methyl, p. 83 trityl, pp. 83-84 benzyl, pp. 84-85 trialkyl silyl, p. 85] acetals and ketals, pp. 85-92 modifications at C-1 [reduction of aldehydes and ketones, pp. 92-93 reduction of thioacetals, p. 93 oxidation, pp. 93-94 chain elongation, pp. 94-98 chain length reduction, pp. 98-99 substitution at the reducing carbon atom, pp. 99-103 formation of gycosides, pp. 103-105 formation of glycosidic linkages between monosaccharide residues, 105-108] modifications at C-2, pp. 108-113 modifications at C-3, pp. 113-120 modifications at C-4, pp. 121-124 modifications at C-5, pp. 125-128 modifications at C-6 in hexopy-ranoses, pp. 128-134. 

There are diffent pathways by which all phenolic compounds are synthesized [6,7]. The shikimate/arogenate pathway leads, through phenylalanine, to the majority of plant phenolics, and therefore we shall centre the present revision on the detailed description of this pathway. The acetate/malonate pathway leads to some plant quinones but also to various side-chain-elongated phenylpropanoids (e.g. the group of flavonoids). Finally, the acetate/mevalonate pathway leads by dehydrogenation reactions to some aromatic terpenoids. 

Mode of action Like acyclovir, ganciclovir is activated through conversion to the nucleoside triphosphate by viral and cellular enzymes, the actual pathway depending on the virus. Cytomegalovirus is deficient in thymidine kinase, and therefore forms the triphosphate by another route. The nucleotide competitively inhibits viral DNA polymerase and can be incorporated into the DNA to decrease the rate of chain elongation. 

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