Why You Need Linoleate

Polyunsaturated fatty acids (PUFAs) are long chain fatty acids with multiple double bonds. Monday's molecule was linoleate or cis, cis -Δ^9,12- octadecadienate. It's an 18-carbon fatty acid with double bonds at positions 9 and 12. PUFA's are essential components of many biochemical pathways. (Note that this fatty acid is a normal cis fatty acid and not a trans fatty acid.)

The standard route for synthesis of PUFAs requires specific enzymes that create the double bonds at fixed positions. These enzymes are called desaturases. Other enzymes can extend the fatty acid chain from 18 carbons (18 carbons are the longest chains made by the normal fatty acid synthesis pathway). These enzymes are called elongases.

The combination of various desaturases and elongases will result in the synthesis of a wide variety of complex polyunsaturated fatty acids. One of these, arachidonate, is the precursor for synthesis of many eicosanoids—a class of compounds that includes the hormones prostaglandins, leukotrienes, and thromboxane.

Arachidonate is made from linoleate.

The first step in the pathway is activation of linoleate by attaching a cofactor called coenzyme A. The result is linoleoyl CoA, which is then converted to arachidonoyl CoA by the action of two desaturases and an elongase.


Now, here's the catch. Most eukaryotes contain a variety of desaturases that can create double bonds as far as 15 carbons away from the the carboxyl end of a fatty acid (i.e., at position 15). Mammals have lost some of these desaturase enzymes so they can't make any PUFA with a double bond beyond position 9. They (we) can't make linoleate even though it is absolutely required for life. We need to get it from our diet.

Tomorrow we'll learn how arachidonoyl-CoA is converted to prostaglandins and how aspirin, ibuprofen, acetaminophen, and other NSAIDS block the synthesis.