Desaturation, of fatty acids

Cyanobacteria, prokaryotic algae that perform oxygenic photosynthesis, respond to a decrease in ambient growth temperature by desaturating the fatty acids of membrane lipids to compensate for the decrease in the molecular motion of the membrane lipids at low temperatures. During low-temperature acclimation of cyanobacterial cells, the desaturation of fatty acids occurs without de novo synthesis of fatty acids [110, 111]. All known cyanobacterial desaturases are intrinsic membrane proteins that act on acyl-Hpid substrates. 

A shift in temperature from 38 to 22 °C leads to desaturation of fatty acids in Anabaena variabilis [110], resulting in control of the fluidity of the plasma membrane. Mutants have been isolated in Synechocystis PCC 6803 that were defective in desaturation of fatty acids, and the growth rate of one of these mutants was much lower than that of the wild-type at 22 °C [112]. It turned out that the mutant strain had a mutation in the gene desA, and when the wild-type allele was introduced into the chilling-sensitive cyanobacterium Anacystis nidulans, it resulted in increasing the tolerance of that strain to low temperature [113]. These experiments nicely demonstrate the existence of a mechanism of adaptation to low temperature in a chilling-tolerant cyanobacterium. 

Chapter 19) Adrenal cortex Liver Fatty acid synthesis Elongation of fatty acids (Chapter 11) Desaturation of fatty acids Detoxification reactions... 

The reduced coenzyme NADPH is required for the reduction reactions shown in Figure 11.5. It is also required for elongation and desaturation of fatty acids. The major source of NADPH for these reactions is the pentose phosphate pathway, which is described in detail in Chapter 6. 

Figure 3.12 Elongation and/or desaturation of fatty acids in the mammary gland.

Desaturation of Fatty Acids Requires a Mixed-Function Oxidase... 

Monounsaturated S-CoA HGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates. 

As a result of impaired activity of acetyl CoA and propionyl CoA carboxylases, there are changes in the fatty acid composition of lipids in the lymphocytes of biotin-deficient rats. There is an increase in the proportion of long-chain fatty acids (C22 0 to C30 0) and odd-carbon fatty acids (Cl 5 0 to C29 0), with a decrease in the proportion of unsaturated fatty acids and the ratio of ds-vaccenic acid (C18 l )9) palmitoleic acid (C16 lft)6), which is indicative of impaired elongation and desaturation of fatty acids (Liu et al., 1994). 

Figure 22.29. Electron-Transport Chain in the Desaturation of Fatty Acids.

Desaturation of fatty acids is a complex process that requires 02, NADPH, and cytochrome b5. 

In animals, desaturation of fatty acids requires a fatty acyl-CoA desaturase (Figure 18.32). The enzyme that creates oleic acid and palmitoleic acid from stearate and palmitate, respectively, is called a A-9 enzyme, because it creates a double bond nine carbons from the carboxyl group of the fatty acids. Similar enzymes in mammalian systems include A5 and A6 desaturases, which are under complex hormonal control. 

Desaturation of fatty acids involves a process that requires molecular oxygen (O2), NADH, and cytochrome dj. The reaction, which occurs in the endoplasmic reticulum, results in the oxidation of both the fatty acid and NADH (Fig. 33.18). The most common desaturation reactions involve the placement of a double bond between carbons 9 and 10 in the conversion of palmitic acid to palmitoleic acid (16 1, A ) and the conversion of stearic acid to oleic acid (18 1, A ). Other positions that can be desaturated in humans include carbons 4, 5, and 6. 

Fig. 33.18. Desaturation of fatty acids. The process occurs in the endoplasmic reticulum and uses molecular oxygen. Both the fatly acid and NADH are oxidized. Human desaturases cannot introduce double bonds between carbon 9 and the methyl end. Therefore, m is equal to or less than 7.

Cultured heart cells responded rapidly to fatty acids administered to the medium. Heated fat produced lower levels of unsaturated fatty acids in the PL fractions, and a greatly increased level of arachidonic acid in the TG fractions (15) In the livers of rats fed heated fats, Rao et al. (50) showed a rapid rate of elongation and desaturation of fatty acid chains. 

The desaturation of fatty acids is usually assayed by incubating radioactive fatty acids with microsomes in the presence of appropriate cofactors. This general protocol has been used by many investigators to assay A9, A6, and A5 desaturase activities. It was thus assumed that 7,10,13,16-22 4 and 7,10,13,16,19-22 5 were desaturated by a microsomal A4 desaturase. In 1991, we showed that when rat liver microsomes were incubated with [1- C]7,10,13,16,19-22 5, it was not desaturated to 4,7,10,13,16,19-22 6. However, when malonyl-CoA was included in the incubation, the substrate was chain elongated to 9,12,15,18,21-24 5, which was then desaturated, at position-6, to yield 6,9,12,15,18,21-24 6. When [1- C]7,10,13,16,19-22 5 and the two [3- C]-labeled 24-carbon acids were incubated with hepatocytes, all three acids were metabolized to esterified [1- C]4,7,10, 13,16,19-22 6 (19). The findings implied that 4,7,10,13,16, 19-22 6 was made from 9,12,15-18 3 as follows ... 

The mechanism postulated for the fatty acid cycle would suggest that the intermediary reactions of fatty acids are CoA dependent, including the saturation and desaturation of fatty acids, as well as changes in the length of the carbon chain. 

Stymne, S Griffiths, G Stobart, K. Desaturation of fatty acids on complex-lipid substrates. In Stumpf PK, Mudd JB, Nes WD, editors. The Metabohsm, Structure, and Function of Plant Lipids. NY Plenum Press, 1987,405-412. 

Fig. 11. Various hypotheses proposed by which higher plants may attain high levels of unsaturated fatty acids in their chloroplast membrane galactolipids. (a) Phosphatidylcholine acts as a carrier molecule involved in the desaturation, (b) Desaturation of fatty acids occurs after formation of the galactolipid molecule, (c) Desaturation occurs before formation of the galactolipid molecule. In the first hypothesis, all the desaturases involved are confined in the chloroplast in the second hypothesis, the conversion of 18 1 to 18 2 is maximal in microsomes," whereas desaturation of 18 2 to 18 3 is highest in chloroplast membranes, (d) Deacylation-reacylation mechanism in which X can be a CoA-thioester, a polar lipid, etc. D, Desaturases T, acyl-ACP thioesterase e.r., endoplasmic reticulum.

Other factors that have already been shown to modify in vitro the A6 desaturation of fatty acids are the concentration of ATP, (Brenner and Catala, 1971) and acceptors of acyl CoA as lysophospho-... 

Since insulin enhances A6 desaturation of fatty acids we suspected that hyperglucemic hormones should depress the activity through a kind of yin- yang mechanism. 

Microsomal desaturation of fatty acids. Two-month-old female Wistar rats fed on Purina chow ad libitum were used. When specified, some rats were fasted for 48 hr and then refed on a diet containing 35% protein (Peluffo and Brenner, 1974). Liver microsomes were separated by differential centrifugation at 100,000 xg in the cold in the way described by Castuma et al, 1972. 

---