Fatty acyl-CoA desaturases

The desaturation process is particularly interesting as it provides an example of a microsomal (as opposed to mitochondrial) electron transport system. The enzymes responsible, fatty acyl-CoA desaturases, are examples of mixed function oxidases... 

There are several fatty acyl-CoA desaturases. Stearoyl-CoA desaturase [EC 1.14.99.5] (also referred to as acyl-CoA desaturase, fatty acid desaturase, and A -desaturase) catalyzes the reaction of stearoyl-CoA with dioxygen and a hydrogen donor (AH2) to produce oleoyl-CoA, two water molecules, and A. The enzyme requires iron as a cofactor. Linoleoyl-CoA desaturase [EC 1.14.99.25], also referred to as A -desaturase, cata-... 

LIPID TRACER KINETICS Fatty acyl-CoA desaturases,... 

Fatty acyl-CoA desaturases are terminal oxidases of a membrane-bound enzyme complex that also includes cytochrome b5 and cytochrome b5 reductase (Bloomfield and Bloch, 1960). They remove substrate hydrogen atoms at a position determined by the specificity of the enzyme. They play essential roles in regulating membrane fluidity and are also involved in insect lipid and pheromone metabolism. They share the presence of three highly conserved histidine-rich sequences (H-boxes) that coordinate the diiron-oxo structure at the active sites (Shanklin and Cahoon, 1998) and four hydrophobic a helices that appear to anchor the protein into the lipid bilayer and situate the H-boxes in their correct position in the active site. 

After the first three molecular characterizations of animal desaturases from rat liver (Thiede et al., 1986), mouse adipose tissue (Ntambi et al., 1988) and carp (Tiku et al., 1996), a Drosophila desaturase was isolated in 1997 (Wicker-Thomas et al., 1997). Since then, numerous studies have been made on lepidopteran desaturases involved in nonhydrocarbon short-chain pheromones (Knipple et al., 1998 reviewed in Knipple and Roelofs, 2003). In Drosophila, there are seven fatty acyl-CoA desaturase genes, which are all located on chromosome III (Figure 4.1), but only three desaturases appear to be involved in hydrocarbon synthesis. In the cricket, a desaturase has been characterized but there is no evidence that this desaturase is involved in pheromone biosynthesis (Riddervold et al., 2002). On the other hand, the desaturase isolated from the housefly is probably involved in both lipid and pheromone biosynthesis (Eigenheer et al., 2002). 

The mammalian acyl desaturases are components in mini-electron transport systems on the surface of the endoplasmic reticulum, for example the A -fatty acyl-CoA desaturase complex ... 

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. 

Fatty acyl-CoA desaturase is an animal enzyme that catalyzes cis bond formation in stearic acid (to form oleic acid) and palmitic acid (to form palmitoleic acid). The unusual reaction scheme is depicted in Figure 18.32. 

See also Fatty Acids, Table 10.1, Synthesis of Long Chain Fatty Acids, Fatty Acid Desaturation, Fatty Acid Synthase, Palmitate Synthesis from Acetyl-CoA, Fatty Acyl-CoA Desaturase... 

Palmitate Synthesis from Acetyl-CoA, Fatty Acyl-CoA Desaturase... 

Moreau, R.A., Pollard, M.R., Stumpf, P.K., 1981. Properties of a A5-fatty acyl-CoA desaturase in the cotyledons of developing Limnanthes alba. Arch. Biochem. Biophys. 209,376-384. 

Figure 1. Electron transport chains of the endoplasmic reticulum. (A) Microsomal acyl-Co A desaturation system composed of NADH-cytochrome reductase, cytochrome fos (a flavoprotein), and fatty acyl-CoA desaturase. (B) Microsomal hydroxylase system depicting participation of the NADPH-cytochrome P-450 reductase (a flavoprotein), cytochrome P-450, and phosphatidylcholine. The role of the phospholipid appears to be in enhancing interaction of the proteins. The reduced form of the hemoprotein cytochrome P-450, on addition of carbon monoxide, envinces a Soret maximum at 450 nm, accounting for its designation. There is evidence that these two systems (A and B) interact in the membrane.

The desaturation of positions 1 and 2 of the alkyl chain to form an alkenyl chain is catalysed by cell free extracts of intestinal epithelial cells, tumour cells and brain. The enzyme is present in the microsomal fraction but the reaction is stimulated by a high molecular weight, heat-labile factor in the soluble cytosol. The fact that a reduced pyridine nucleotide and molecular oxygen are absolute requirements and that the reaction is inhibited by cyanide but not by CO, strongly suggest that this enzyme is very similar to the fatty acyl-CoA desaturase described in section 3.2.4. This provides another interesting example of an enzyme catalysing a modification of a hydrocarbon chain in the intact lipid molecule. 

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