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... 

Desaturation of a saturated bond to produce an unsaturated fatty acid (the conversion of -CH2-CH2- to -CH=CH-) is catalysed by enzymes known as acyl-CoA desaturases. 

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,... 

ACYL-CoA DESATURASE ALKANE HYDROXYLASE AMINE OXIDASES... 

Rosenfield C.-L., You K. M., Marsella-Herrick P., Roelofs W. L. and Knipple D. C. (2001) Structural and functional conservation and divergence among acyl-CoA desaturase-encoding genes of two noctuid species, the com earworm, Helicoverpa zea, and the cabbage looper, Trichoplusia ni. Insect Biochem. Molec. Biol. 31, 949-964. 

Yoshiga T., Okano K., Mita K., Shimada T. and Matsomoto S. (2000) cDNA cloning of acyl-CoA desaturase homologs in the silkworm, Bombyx mori. Gene 246, 339-345. 

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). 

Both plants and animals use mixed function oxidases (simultaneously oxidize two substrates) Acyl-CoA desaturases localized on the ER. Similar mixed function oxidases are also used to modify structural components of cells, hormones etc. so we will use the acyl-CoA desaturase as an example for this group of enzymes. In the acyl-CoA desaturase reaction molecular oxygen is used to oxidize both a fatty acid and NADH, each providing two of the the four electrons needed by the oxygen ... 

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 ... 

According to its solubility these enzymes can be classified into two non evolutively related groups the soluble acyl carrier protein (AGP) desaturases and the membrane-bound desaturases, which includes the acyl-lipid desaturases and the acyl-CoA desaturases. The soluble AGP desaturases introduce double bonds into fatty acids esterified to AGP, and are found in the stroma of plant plastids (Shanklin and Gaboon, 1998) and some bacteria, as Mycobacterium and Streptomyces (Phetsuksiri et al., 2003). The acyl-lipid desaturases, that... 

Like the acyl-CoA desaturases (Chapter 7), the 1 -alkyl desaturase exhibits the typical requirements of a microsomal mixed-function oxidase. Molecular oxygen, a reduced pyridine nucleotide, cytochrome b, cytochrome reductase, and a terminal desaturase protein that is sensitive to cyanide are all required. The precise reaction mechanism responsible for the biosynthesis of ethanolamine plasmalogens is unknown, but it is clear from an investigation with a tritiated fatty alcohol that only the 15 and 25 (erythro)-labeled hydrogens are lost during the formation of the alk-l -enyl moiety of ethanolamine plasmalogens. 

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... 

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