Stearyl-CoA

This pathway (the microsomal system ) elongates saturated and unsaturated fatty acyl-CoAs (from Cjg upward) by two carbons, using malonyl-CoA as acetyl donor and NADPH as reductant, and is catalyzed by the microsomal fatty acid elongase system of enzymes (Figure 21-5). Elongation of stearyl-CoA in brain increases rapidly during myehnation in order to provide C22 and C24 fatty acids for sphingoEpids. 

The process of elongation of C16 to C18 (stearyl-CoA) is independent of FAS but is chemically identical to one cycle of FAS reactions with malonyl-CoA as the C2 donor. Stearyl-CoA may be further elongated if necessary. 

Several cycles are required for complete degradation of long-chain fatty acids—eight cycles in the case of stearyl-CoA (C18 0), for example. The acetyl CoA formed can then undergo further metabolism in the tricarboxylic acid cycle (see p. 136), or can be used for biosynthesis. When there is an excess of acetyl CoA, the liver can also form ketone bodies (see p. 312). 

The regulation of the chain length specificity to produce the specific blend of hydrocarbons often used in chemical communication appears to reside in the microsomal fatty acyl-CoA elongase reaction and not in the reductive conversion of fatty acyl-CoAs to hydrocarbon. The American cockroach produces three major hydrocarbons n-pentacosane, 3-methylpentacosane and (Z,Z)-9,12-heptacosadiene (Jackson, 1972). Studies with microsomes from integument tissue showed that stearyl-CoA was elongated up to a 26 carbon acyl-CoA that could serve as the precursor to n-pentacosane. In contrast, linoleoyl-CoA... 

Kinsella, J.E. 1972. Stearyl CoA as a precursor of oleic acid and glycerolipids in mammary microsomes from lactating bovine possible regulatory step in milk triglyceride synthesis. Lipids. 7, 349-355. 

McDonald, T.M., Kinsella, J.E. 1973. Stearyl-CoA desaturase of bovine mammary microsomes. Arch. Biochem. Biophys. 156, 223-231. 

Ozols, J. 1997. Degradation of hepatic stearyl CoA A9-desaturase. Mol. Biol. Cell. 8,2281-2290. 

Statins, 330, 369 Stearic acid, 362-363 StearyL-CoA desahiraso, 746-747 Stellate cells, 556 Stem cells, 512, 753... 

The synthesis of imsaturated fatty acids is described xmder Essential Fatty Acids in Chapter 9. One of the steps involves the A -desaturase, also called stearyl-CoA... 

The yield from the oxidation of stearyl-CoA is calculated as follows ... 

Two ATP are requited to form stearyl-CoA from stearate to give a total of 120 ATP. 

Enoch, H.G., Catala, A. and Strittmatter, P. Mechanism of rat liver microsomal stearyl-CoA desaturase. Studies of the substrate specificity, enzyme-substrate interactions, and the function of lipid. J Biol Chem, 251 (1976) 5095-5103. 

Stearic acid —> Steaiyl-CoA (activation step) 2. Stearyl-CoA — 9 acetyl-CoA (8 cycles of P-oxidation) +8 +8 -2... 

Liver has the enzyme activity to catalyse the introduction of a single double bond into saturated fatty acids. Stearyl-CoA desaturase (EC.l.14.99.5 reaction 4.3), which catalyses the synthesis of oleic and palmitoleic acids, is present on the endoplasmic reticulum and is hormonally regulated Goshi Aranda, 1979). 

JoshL V.C. Aranda, L.P. (1979). Hormonal regulation of the termiruil enzyme of microsomal stearyl CoA desatur[Pg.245]

Kouba, M., Bemard-Griffiths, M.-A. Lemarchal, P. (1993). Liver stearyl-CoA desaturase activity and fatness in birds. In vitro studies in the growing turkey and chicken. Comp. Biochem. Physiol, 105A, 359-62. 

Legrand, P. Lemarchal, P. (1992). Stearyl-CoA desaturase activity and triglyceride secretion in isolated and cultured... 

Kinsella, J.E. (1972) Stearyl CoA as a Precursor of Oleic Acid and GlyceroUpids in Mammary Microsomes from Lactating Bovine Possible Regulatory Steps in Milk Triglyceride Synthesis, Lipids 7,349-355. 

The detailed molecular mechanism of the conversion of saturated into unsaturated fatty acid is not known. But already in 1936, Schoenheimer and Rittenberg demonstrated that deuterium-labeled stearic acid was converted to oleic acid in mammalian tissues. The aerobic conversion of stearate to oleate or palmitate to palmitoleate was studied in yeast. The conversion requires O2 and NADPH and the active substrate is stearyl CoA or palmityl CoA. 

The fatty acid desaturase system was one of the first microsomal enzymes for which a lipid requirement was established. Using Fleischer s procedure of aqueous acetone extraction (Lester Fleischer, 1961) we were able to reduce the desaturase activity of hen liver microsomes to very low levels and restore activity completely with a mixture of lipids isolated from the microsomes (Holloway Peluffo, 1964 Jones at al., 1969). Shortly after this observation cytochrome bs was implicated in the desaturation process (Oshino et al., 1966). Progress in the isolation and purification of the stearyl CoA desaturase has been slow and it is only in the last two years that the complete resolution and reconstitution of the stearyl CoA desaturase has been achieved by Strittmatter and co-workers (Strittmatter et al., 1974). 

Milestones along the way have, I think, been the initial postulation by Sato and co-workers of a role for cytochrome bs (Oshino et al., 1966) and later their spectral studies showing the acceleration of cytochrome bs re-oxidation by added stearyl CoA (Oshino et al., 1971). 

The standard assay system contained 60 mM potassium phosphate (pH 7.2), 100 yM NADH, 20 yM 1- C -stearyl CoA, protein and other components, and water to a final volume of 0.5 ml. Incubations were at 37°C for 15 min in air. The product l- c -oleate was separated as the methyl ester, after saponification and methylation, by thin layer chromatography on AgNO3impregnated Silica Gel H (Jones et al., 1969). 

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