Mechanism of chain elongation

IPP is the near-universal prenyl acceptor in the IPPS enzymes ( irregular monoterpene synthases are exceptions (vide infra)). In the protein prenyltransferases, IPP is absent, and a cysteine sulphur atom from the target protein acts as the electron-rich prenyl acceptor. 

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Its formation during roasting could result from a trimolecular reaction between ethylglyoxal, ammonia and acetaldehyde resulting from the Strecker degradation of alanine. The mechanism of chain elongation reactions of glyoxal has been elucidated by Yaylayan and Keyhani (1998). 

KOYAMA, T., OGURA, K., Enzymatic mechanism of chain elongation in isoprenoid biosynthesis, in Comprehensive Natural Products Chemistry, Vol. 2, Isoprenoids Including Carotenoids and Steroids (D.D. Cane, ed.) Elsevier, Amsterdam. 1999, pp. 69-96. 

Fig. 18. Mechanism of chain elongation in the ScUmonella 0-antigen. The growing chain, represented by a hexasaccharide unit, is transferred to the lipid-linked trisac-chaiide repeating sequence. The sugar residues from the trisaccharide unit, which are underlined, me at the reducing end of the resulting iionaacnharide unit.

This stimulated interest in the mechanism of chain elongation and when the main details of the -oxidation pathway (the means by which fatty acids are broken down two carbon atoms at a time, section 3.3.1) were worked out in the early 1950s it was natural for many biochemists to ask the question can )8-oxidation be reversed in certain circumstances to synthesize fatty acids instead of breaking them down ... 

All polyketides use the same general mechanism for chain elongation. Acetyl coenzyme A provides acetate (C2) units, which are condensed by a ketosynthase (KS). This in turn catalyzes condensation of the growing chain onto an acyl carrier protein (ACP), as generalized in Fig. 1.4. Enzymes such as ketoreductase (KR), enoyl reductase (ER), and dehydratase (DH) establish the oxidation state of caibon during translation, imparting structural diversity. Successive translation of each module leads to a chain of the required length that is eventually passed to thioeste-rase (TE), which releases the chain as a free acid or lactone. 

The monomeric mechanism of chain assembly is characteristic for homopolysaccharides, which constitute the most difficult case for biosynthetic studies, as accumulation of intermediates could not be induced by removal of one of the glycosyl donors required for chain elongation. Among these polymers, the most extensive information has been obtained for polymers of JV-acetylneuraminic acid, namely, the capsular polysaccharides (36 and 37) of E. coli K1 (Ref. 354) and Neisseria meningitidis type c (Ref. 355), respectively. CMP-NeuAc serves as the glycosyl donor in the formation... 

Mechanism of action Upon entry into the host cell, didanosine is biotransformed into ddATP through a series of reactions that involve phosphorylation of the ddl, amination to ddAMP and further phosphorylation. The resulting ddATP is incorporated into the DNA chain like AZT, causing termination of chain elongation. 

Several architectural paradigms are known for polyketide and fatty acid synthases. While the bacterial enzymes are composed of several monofunctional polypeptides which are used during each cycle of chain elongation, fatty acid and polyketide synthases in higher organisms are multifunctional proteins with an individual set of active sites dedicated to each cycle of condensation and ketoreduction. Peptide synthetases also exhibit a one-to-one correspondence between the enzyme sequence and the structure of the product. Together, these systems represent a unique mechanism for the synthesis of biopolymers in which the template and the catalyst are the same molecule. 

Tetracycline targets protein synthesis in Plasmodium via a similar mechanism to that seen in bacteria inhibition of chain elongation and peptide bond formation. Eflornithine interferes with the metabolism of the amino acid ornithine in T. brucei gambiense by acting as a suicide substrate for the enzyme ornithine decarboxylase. 

The biosynthesis of fungal aliphatic polyketides by a processive mechanism is further demonstrated by the successful incorporation of chain elongation intermediates as their NAC thioesters in several experiments [119, 120]. These... 

After the induction time, chain scissioning became uninhibited and was manifested by loss of elongation. Mechanisms of chain scissioning and stabilization are discussed. 

In a later study (Whereat and Orishimo, 1968), cholesterol was administered by stomach tube without Wesson oil. In the latter instance, almost all the fatty acids contained more label in the cholesterol fed group but the greatest increase in incorporation was in 18 2 and the next most increased was 18 1. The specific activity of 18 2 had increased 6-fold. The change of the major labeled product from 18 2 to 20 2 by the addition of large amounts of 18 2 to the diet was further evidence that the major synthetic mechanism was chain elongation. 

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