potential roles the products of these enzymes have in regulating
Fatty acids are synthesized from acetyl-CoA
and malonyl-CoA through a series of reactions shown in Figure 1.
The de novo synthesis of fatty acids occurs in two distinct cellular
compartments. Palmitate (16:0) is synthesized from acetyl-CoA and
malonyl-CoA in the cytoplasm by the enzymes acetyl-CoA carboxylase-1
and fatty acid synthase. The synthesis of fatty acids longer than
16 carbons takes place in microsomes and utilizes malonyl-CoA as
the carbon source. These enzymes have only been partially characterized
and not all have been identified.
The mammalian enzymes that elongate palmitic acid (16:0) and
very long chain fatty acids (>C18) have been localized to the
endoplasmic reticulum (ER) and are shown schematically in Figure
2. The initial condensation reaction is the regulated and rate-controlling
step in microsomal fatty acyl elongation. We reported the cDNA
cloning and characterization of a murine long chain fatty acyl
elongase (LCE), now designated ELOVL6. Overexpression of ELOVL6
in cells resulted in the enhanced addition of 2-carbon units to
C12-C16 fatty acids and evidence was provided that LCE catalyzed
the initial condensation reaction of long chain fatty acid elongation.
A line of knockout mice with a disrupted ELOVL6 gene is now being
characterized to determine the physiological consequences of the
induced mutation for lipid homeostasis and in the development