Wax ester biosynthesis

Kayama, M. and Nevenzel, J. (1974). Wax ester biosynthesis by midwater marine animals. Marine Biology 24,79-285. 

Li, F Wu, X Lam, P Bird, D Zheng, H Samuels, L Jetter, R Kimst, L. Identification of the wax ester synthase/acyl-coenzyme A Diacylglycerol acyltransferase WSDl required for stem wax ester biosynthesis m. Arabidopsis. Plant Physiol, 2008, 148, 97-107. 

Reversal of an esterase-type reaction was the only mechanism demonstrated for wax ester biosynthesis until 1967 (Kolattukudy, l%7a). Under physiological conditions an acyl transfer mechanism would be expected to be involved in such ester synthesis. Because of the high thioesterase activ-... 

Wax ester biosynthesis probably involves an acyl transfer mechanism. The high thioesterase activity found in crude plant extracts makes it difficult to demonstrate acyl-CoA involvement in wax ester synthesis. However, partial purification of an acetone powder extract from the leaves of B. oleracea gave a protein fraction that catalyzed an acyl-CoA-dependent esterification of fatty alcohols (222). Additionally the acetone powder extract from B. oleracea leaves appeared to catalyze the direct transfer of acyl moieties from phospholipids to fatty alcohols. The leaf extract also catalyzed under appropriate conditions the esterification of fatty alcohols to free fatty acids. The transacylase mechanism is likely to be the main mechanism of wax ester synthesis in vivo. The fact that labeled wax esters were synthesized by a membrane-bound microsomal fraction from Hordeum vulgare leaves following incubation with radioactive alcohols, but not after incubation with free fatty acids (17), is consistent with the proposed acyl transfer mechanism. In E. gracilis the acyl-CoA reductase is functionally coupled to the acyl transferase (227). Both of these activities were solubilized from the microsomes... 

Nevenzel, J.C. (1970). Occurrence, function and biosynthesis of wax esters in marine organisms. Lipids 5,308-319. 

Next to fumarate reduction, some organisms use specific reactions in lipid biosynthesis as an electron sink to maintain redox balance in anaerobically functioning mitochondria. In anaerobic mitochondria two variants are known the production of branched-chain fatty acids and the production of wax esters. The parasitic nematode Ascaris suum reduces fumarate in its anaerobic mitochondria, but instead of only producing acetate and succinate or propionate, like most other parasitic helminths, this organism also use the intermediates acetyl-CoA and propionyl-CoA to form branched-chain fatty acids (Komuniecki et al. 1989). This pathway is similar to reversal of P-oxidation and a complex mixture of the end products acetate, propionate, succinate and branched-chain fatty acids is excreted. In this pathway, the... 

Garver et al. (1992) developed an assay that measures the activity of the acyl-CoA alcohol transacyiase involved in the biosynthesis of storage liquid wax esters in jojoba and some microbes and algae. 

Wax esters are another useful marine lipid class, which are now historical when derived from the heads of sperm whales. Although various marine invertebrates contain wax esters (110), there is an unexploited resource in relatively small fish called myctophids. These fish can be caught by modem fishery technology as was shown in South Africa some decades ago, but the use of any oil and meal produced would have to be carefully considered. The biosynthesis of their wax esters has recently been resolved (111) and reviews most questions on that topic that were... 

In a series of labeling experiments, the biogenesis of esters and alcohols by fruit tissue slices was investigated (7y .) While (U—1 4c) -acetate and (U-1 c) -butyrate were incorporated into the corresponding esters by postclimacteric banana tissue, (U-14c)-octanoate was transformed in climacteric and postclimacteric banana tissues into caproic and butyric acid by B-oxidation and into heptanoic acid by ot-oxidation (9). In addition, 1-octa-nol, Z-4-hepten-2-ol, pentanol-2 and the corresponding esters were labeled. The biosynthesis of alcohols and esters is an analogous reaction to the formation of wax esters as outlined by Kolattukudy ( O). Octanoyl-CoA is reduced by an acyl-CoA reductase (NADH dependent) to octanal which is further transformed into 1-octanol by an... 

The biosynthesis and degradation of marine wax esters and hydrocarbons has been reviewed by Sargent et al. (1976). So far as functions are concerned the wax esters may serve as a source of metabolic energy or of metabolic water, for buoyancy, as biosonar (e.g. in the head regions of whales, porpoises) or for thermal insulation. Further details can be found in Sargent et al, (1976). 

Wax esters from jojoba (Simmondsia chinensis, Simmonds-iaceae) consist of molecules with mostly C20 acid (monoene) esterified with about an equal mixture of C20 and C22 alcohols (monoene) (Yermanos, 1978 1981 Miwa, 1971). In studies of the biosynthesis of the fatty acids and alcohols in slices of fresh jojoba cotyledons, a radioactive label from glucose was incorporated into all carbons of both the C20 and C22 acids and alcohols. In contrast, exogenous acetate was used almost entirely for chain elongation from endoge-... 

Fig. 4.1. Biosynthesis of long-chain fatty acids, aldehydes, alcohols, and wax esters. (Kolattukudy, 1980 modified and used with permission of tl copyright owner, Academic Press, Orlando, FL).

Fig. 11. Biosynthesis of very long acids, aldehydes, alcohols, and wax esters.

Biosynthesis of Fatty Acids, Triacylglycerols, and Wax Esters in Plants. 100... 

Biosynthesis of wax esters involves the condensation of a long chain fatty alcohol with fatty acyl-CoA... 

How the aliphatic monomers are incorporated into the suberin polymer is not known. Presumably, activated co-hydroxy acids and dicarboxylic acids are ester-ified to the hydroxyl groups as found in cutin biosynthesis. The long chain fatty alcohols might be incorporated into suberin via esterification with phenylpro-panoic acids such as ferulic acid, followed by peroxidase-catalyzed polymerization of the phenolic derivative. This suggestion is based on the finding that ferulic acid esters of very long chain fatty alcohols are frequently found in sub-erin-associated waxes. The recently cloned hydroxycinnamoyl-CoA tyramine N-(hydroxycinnamoyl) transferase [77] may produce a tyramide derivative of the phenolic compound that may then be incorporated into the polymer by a peroxidase. The glycerol triester composed of a fatty acid, caffeic acid and a>-hydroxy acid found in the suberin associated wax [40] may also be incorporated into the polymer by a peroxidase. 

Despite the sequence similarity between the CERl and GLl proteins, their biochemical function is unclear since mutations at each gene affect the respective cuticles differently. CERl has been predicted to code for an aldehyde decarbonylase (Aarts et al., 1995), an enzyme required for the production of the alkane fraction of the cuticular waxes of this species. Indeed, mutations at the CERl locus cause an enrichment of the aldehydes and a depletion of the alkanes and alkane-derived metabolites (ketones and secondary alcohols). In maize however, its unlikely that gll codes for an aldehyde decarbonylase. This conclusion is based upon the fact that alkanes account for a very small portion of the cuticular waxes of wild-type maize seedlings (about 1%), and because mutations at the gll locus qualitatively and/or quantitatively affect the accumulation of fatty aldehydes, alcohols, and the ester components of the maize cuticular waxes. Therefore, even though the GLl and CERl proteins share similar structures, they may in fact perform different functions in cuticular wax biosynthesis. Alternatively, both proteins may perform similar, but as yet unidentified, function(s). 

The aliphatic components of suberin form polyester domains that are attached to the phenolics as indicated above (see Fig. 6.4.7). Activated cu-hydroxy acids and dicarboxylic acids are probably involved in the esterification as shown in cutin biosynthesis (232). It was proposed that the long-chain fatty alcohols found in suberin might be incorporated into the suberin polymer by peroxidase-catalyzed polymerization of phenylpropanoic acid esters of these alcohols (232), such as the ferulic acid esters of C18-C28 alcohols frequently found in suberin-as-sociated waxes (Table 6.4.2). 

Modulation of epidermal lipid biosynthesis has been reported to boost drag delivery. It has also been suggested that it is both the hydrophobic nature of the lipids as well as their tortuous, extracellular localization that are responsible for the restriction in the transport of most molecules across the stratum comeum. The function of this barrier depends on three key lipids cholesterol, fatty acid, or ceramides. Delays of synthesis ceramides in the epidermis have been reported as means of barrier perturbation. Inhibitors of lipid synthesis were used to enhance the trans-A cmaV dehvery of hdocaine or caffeine. Alteration of barrier function was produced by the fatty acid synthesis inhibitor S-(tetradecyloxy)-2-furancarboxylic acid, the cholesterol synthesis inhibitor fluvastatin, or the cholesterol sulfate, which resulted in a further increase in lidocaine absorption (38). The major components of sebaceous lipids in the skin are 45-60% TAGs, 25% wax and sterol esters, 12-15% squalene and 10% free fatty acids (39). Some fatty acids, especially unsaturated fatty acids, are well-known skin penetration enhancers. The addition of PC to dermal dosage forms has been reported to increase percutaneous absorption. Lipid disperse systems (LDSs) containing polar lipids, such as PC and glycosylceramide, are also useful for... 

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