Microsomes, fatty acid synthesis

Polyunsaturated fatty acid synthesis is catalyzed by acyl-lipid-desaturases, also named front-end desaturases due to their action mechanism, which proceeds via introduction of double bonds into preformed acyl chains by oxygen and electron-donor dependent desaturation, between the carboxyl group and the pre-existing unsaturation which acts as substrate. For many microsomal desaturases, the electron donors are cytochrome b5, and a small hemoprotein that operates in numerous redox reactions in plants, involving NADH-dependent acyl-group desaturation [200]. 

There is presumptive evidence that the proplastid and the ofl storage organelles differ in function. Thus, Yamada and his colleagues, as well as Simcox et al., have shown that proplastids isolated from developing castor bean endosperm synthesize only oleic acid. However, the major product of fatty acid synthesis in these seeds is triricinoleoylglycerol. Galliard and Stumpf (1966) have shown that the synthesis of ricinoleic acid involves a microsomal preparation (presumably endoplasmic reticulum) which hydroxylates oleoyl-... 

Many studies have revealed that thyroid hormones markedly affect lipid metabolism in man and in several species of animals. Concerning fatty acid biosynthesis it was demonstrated that the administration of thyroxine stimulates the incorporation of l-l c acetate into fatty acids in rats and mice (Dayton et al, I960) (Gompertz and Greenbaum, 1966) (March and Mayer, 1959). According to Gompertz and Greenbaum (1966) these observations appear to be associated with an increase of stearyl-CoA desaturase activity. Moreover Myant and Iliffe (1963) found that rats treated with thyroxine showed an inhibition of acetate incorporation, but not of malonate incorporation, into fatty acids by mitochondria free, subcellular liver preparations. Other authors have shown that the thyrotoxic state was accompanied by an increased incorporation of acetyl-CoA to fatty acid and a rise in the activity of fatty acid synthetase in rat livers (Diamant et al, 1972) (Roncari and Murthy, 1975). However, in vitro studies of fatty acid synthesis in which liver supernatant of 105,000 xg and microsomal preparations were incubated with the hormone showed that thyroxine inhibits de novo synthesis of palmitate and stimulates the desaturation reactions (Faas et al, 1972). 

Microsomal (0-6 desaturases use cytochrome b5 as electron donor to introduce a double bond into the co-6 position of monounsaturated oleic acid to produce polyunsaturated linoleic acid. Thus microsomal -6 desaturases play a vital role in the polyunsaturated fatty acid synthesis in angiosperms. It has been estimated that these enzymes are responsible for more than 90% of the polyunsaturated fatty acid synthesis in non-photosynthetic tissues and developing seeds of oil crops (1). 

A stimulation of the microsomal oleoyl phosphatidylcholine desaturase (ODS) activity followed by an increase of linoleate (18 2) at the expense of oleate (18 1) was observed in both total and microsomal lipids when developing sunflower seeds were transferred to 10°C even for short times [1]. Under these conditions no de novo" fatty acid synthesis was detected. Moreover, the ODS activity was successively increased and reduced by alternate shifting to 10°C and 30 C and a concomitant increase and decrease of 18 2 was observed in the microsomal lipids [2]. Also, we have demonstrated that oleate from triacylglycerols (TAG) was desaturated in cold-induced sunflower seeds and the resulting 18 2 was also found in TAG preferentially at position sn-2 [3]. This turnover of TAG fatty acids was observed in both microsomal fraction and oil bodies and affected to all TAG molecular species containing 18 1 and 18 2. Now we present evidence of the exchange of 18 1 and 18 2 between TAG and other lipids in response to temperature adaptation. 

Synthesis of fatty acids, at least in higher species, has always been considered to be directed toward the production of saturated rather than unsaturated fatty acids, and it is well known that the enzymes in tissue preparations mainly yield the saturated form. The conclusions drawn from the in vitro experiments indicate that the cytoplam assumes a primary function in lipogenesis. The in vivo studies (Fa-varger et al., 1969), such as in perfused rat liver (Rous and Aubry, 1970), have shown, however, that the predominant site of hepatic fatty acid synthesis could be located in the microsomes (Favarger, 1970). In white adipose tissue, the synthesis of fatty acids is mainly... 

NADPH. The elongation differs from the condensation inasmuch as (a) enoyl-CoA produced by dehydration of /3-hydroxyacyl-CoA is a cis compound in fatty acid synthesis via condensation, and a trans compound in microsomal synthesis (b) the intermediates formed by condensation remain protein bound and are not derived from CoA (Bressler and Wakil, 1961, 1962 Brodie et al., 1964) whereas these are released as CoA derivatives in the microsomal synthesis (c) in this case, an acid with the chain containing more than 10 carbons is elongated and (d) the elongation can proceed with the 18-carbon unsaturated acyl-CoA derivatives. 

The most important part of fatty acid synthesis is achieved in vitro in this cell fraction in vivo it occurs in the microsomes. This synthesis is thus extramitochondrial in both cases. Nicotinamides as such cannot difiFiise through the cell membrane (Lehninger, 1951,... 

Howard also found that aortic microsomes utilized both malonyl-CoA and acetyl-CoA for fatty acid synthesis, and the products appeared to be the result of elongation of precursor acyl units. 

Fig. 1. The above pathways for fatty acid synthesis have been demonstrated to be present in the aorta. The thickness of the arrows denotes the author s interpretation of the relative contribution to total synthesis made by the three intracellular sites. The mitochondrial pathway has the largest capacity to utilize acetate for the elongation of available acyl units. The latter are derived from plasma free fatty acid (FFA) and lipolysis of tissue triglyceride (TG). The cytosol has a limited capacity to synthesize fatty acids from acetate because of minimal acetyl-CoA carboxylase (ACC) activity. The significance of fatty acid synthetase (FAS) activity is dubious in the absence of a source of malonyl-CoA. A microsomal elongation-desaturation pathway can synthesize a spectrum of saturated (SAT) and unsaturated (UNSAT) long-chain fatty acids, similar to the products of the mitochondrial system.

Microsomes have been found to stimulate fatty acid synthesis by the soluble eytosol enzymes in several different tissues (Lorch et al.. 

In order to examine the apparently selective inhibition of very long chain fatty acid synthesis in vivo, experiments have been carried out in our laboratories using microsomal fractions these contain endoplasmic reticulum, which is the site of fatty acid elongation (Section 3.2). 

Table 3.17. Action of Ethofumesate (10 M) on Fatty Acid Synthesis by Microsomal Fractions from Germinating Pea Seeds ...

An interesting aspect of the problem of fatty acid synthesis in livercell supernatant is stimulation of activity by microsomes. Explanations of this phenomenon have been based on the effect of microsomes on transacylase reactions but have never been completely convincing because of the inability to demonstrate expected effects on the concen-... 

Foster, D. W., and McWhorter, W. P., 1969, Microsomes, microsomal phospholipids and fatty acid synthesis, /. Biol. Chem. 244 260. 

During catabolic and anabolic processes, a renovation of the molecular cellular components takes place. It should be emphasized that the catabolic and anabolic pathways are independent of each other. Be these pathways coincident and differing in the cycle direction only, the metabolism would have been side-tracked to the so-called useless, or futile, cycles. Such cycles arise in pathology, where a useless turnover of metabolites may occur. To avoid this undesirable contingency, the synthetic and degradative routes in the cell are most commonly separated in space. For example, the oxidation of fatty acids occurs in the mitochondria, while the synthesis thereof proceeds extramitochondrially, in the microsomes. 

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