Elongating enzymes

Zhao, P. et al., Characterization of leachianone G 2"-dimethylallyltransferase, a novel prenyl side-chain elongation enzyme for the formation of the lavandulyl group of sophoraflavanone G in Sophora flavescens Ait. cell suspension cultures. Plant Physiol, 133, 1306, 2003. 

Immediately after its identification DNA polymerase I was generally assumed to be the principal chain elongation enzyme. However, an amber mutant of E. coli deficient in DNA polymerase I (gene polA ... 

Enzyme complexes occur in the endoplasmic reticulum of animal cells that desaturate at A5 if there is a double bond at the A8 position, or at A6 if there is a double bond at the A9 position. These enzymes are different from each other and from the A9-desaturase discussed in the previous section, but the A5 and A6 desaturases do appear to utilize the same cytochrome b5 reductase and cytochrome b5 mentioned previously. Also present in the endoplasmic reticulum are enzymes that elongate saturated and unsaturated fatty acids by two carbons. As in the biosynthesis of palmitic acid, the fatty acid elongation system uses malonyl-CoA as a donor of the two-carbon unit. A combination of the desaturation and elongation enzymes allows for the biosynthesis of arachidonic acid and docosahexaenoic acid in the mammalian liver. As an example, the pathway by which linoleic acid is converted to arachidonic acid is shown in figure 18.17. Interestingly, cats are unable to synthesize arachidonic acid from linoleic acid. This may be why cats are carnivores and depend on other animals to make arachidonic acid for them. Also note that the elongation system in the endoplasmic reticulum is important for the conversion of palmitoyl-CoA to stearoyl-CoA. 

Takahashi, S. and Koyama, T. (2006) Structure and function of cis-prenyl chain elongating enzymes. Chem. Rec., 6, 194-205. 

To design a plant that will produce these oils, it is necessary to clone into the plant of choice (probably sunflower or rapeseed—canola) genes that will code for one or two elongating enzymes (to convert C18 fatty acids into C20 fatty acids... 

This suggests that TNF-ct, which is associated with an inflammatory environment, promotes the appearance of core 1 structures in endothelial cells. Since the core 1 elongation enzyme (/33GnT3) shows a low expression in human endothelial cells (see Section 6.11.13.1), core 2 is expected to be the main carrier of selectin ligands. A reduction in core 2 may be a negative feedback mechanism by which the infiltration of leukocytes to the site of inflammation is reduced. 

Fig. 2.3. Probable pathways of formation of polyenoic adds in avian spedes (Watkins, 1991). The structures of the fatty adds are indicated by their chain length, followed by the number of double bonds, followed by the series. The series relates to the position of the double bond nearest the methyl end of the chain. For example, 183n3 indicates a Ci, fatty add with three double bonds, beginning the third carbon atom from the methyl end of the chain. and A, desaturation enzymes E elongation enzyme PGi.PGj, PG),...

Leonard, AJi., Kelder, B., Bobik, E.G., Chuang, L.-T., Lewis, C.J.,Kopchick,JJ., Mukerji, P., and Huang, Y.-S. (2002) Identification and Expression of Mammalian Very Long-Chain PUFA Elongation Enzymes, Lipids 36,733-740. 

Although the three milkweed species produce different amounts of cis-vaccenate and palmitoleate vs. oleate and linoleate, the endogenous acyl-ACP desaturase activity does not fully account for the differential synthesis. Each of the milkweed species has similar specificity for 16 0 ACP vs. 18 0 ACP. Interactions of the products of desaturation with elongation enzyme systems and thioesterases are likely to be additional factors in driving production of cf5-vaccenate. 

Elongation consists of the sequential condensation of IPP and allylic diphosphate through the action of the prenyl chain elongating enzyme, commonly called prenyl transferase. The reactions catalyzed by prenyltransferases start with the formation of allylic cations after the elimination of pyrophosphate ions, to form allylic prenyl diphosphate. This is followed by addition of an IPP with stereo-specific removal of the proton at the 2-position. This is the key reaction which determines cis- or rrans-configuration of the double bonds contained in the linear isoprenoid chain. Cis-trans isomerism is dependent on the nature of the prenyltransferase involved in elongation catalysis. A comprehensive review of cis- and traAW-prenyltransferases was recently undertaken by Takahashi and Koyama. CA-prenyltransferases are much less well known than their trawi-homologues. 

Galactosyltran erases and N-Acetyl-g1ueosaminyUran erases (elongation enzymes) ... 

Feeding a fat-free diet to rats results not only in the fatty acid changes cited previously but also in increased synthesis of palmitic acid in rats injected intratesticularly with C-acetate or in slices of testes incubated with C-acetate. There was relatively less incorporated into the polyenes in the tissue from the deficient rats (Whorton Coniglio, 1977). It was observed that there was no effect on fatty acid synthetase or on microsomal elongation enzymes, but there was an increase in the acetyl CoA carboxylase activity of testes of the fat-deficient rats. 

The administration of thyroxine to normal rats for several days produced an increase of A9 desaturation activity of liver microsomal preparations. Conversely, A6 desaturation activity decreased significantly under the hormone treatment. These results were attributed to an increase in glucose metabolism. The elongating enzyme system of linoleic acid seems to be insensitive to thyroxine. Neither the desaturation nor the elongation reactions were modified under propylthiouracil treatment of rats. 

The A6 desaturase is a microsomal enzyme but the elongating enzymes may be found in microsomes and mitochondria. Therefore it is possible that the microsomes of HTC cells have been altered. 

Certain biochemical indices are available for determining the presence of either total EFA deficiency or -3 fatty acid deficiency. Linoleic, linolenic and oleic (18 l -9) acids compete for the same desaturation and elongation enzymes that convert these fatty acids to long chain polyunsaturated fatty acids (see Figure 2.3). The desaturases prefer co-3 over -6 over -9 fatty acids (Tinoco et al., 1979). Normally, with sufficient EFA in the diet, tissue levels of eicosatrienoic acid (20 3 -9) are very minor despite the abundance in tissues of its precursor, oleic acid. With total EFA deficiency, tissue levels of eicosatrienoic acid rise concomitant with decreased levels of AA. An increase in this triene/tetraene ratio (20 3 -9/20 4 -6) in blood and tissues is characteristic of total EFA deficiency, but not of -3 fatty acid deficiency (Holman et al., 1964). 

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