How a Liver Enzyme Handles Omega-3 vs Omega-6 Fats at the Molecular Level

This study used computer modeling to look at how a human liver enzyme called CYP2E1 processes two important fatty acids: EPA (an omega-3 found in fish oil) and arachidonic acid, AA (an omega-6). Both fats can be converted by this enzyme into smaller signaling molecules that influence inflammation and other body processes.

Using detailed molecular simulations, the researchers found that EPA and AA sit in the same pocket of the enzyme but interact with it in slightly different ways. EPA tended to form a specific chemical bond with a particular part of the enzyme entrance more often than AA did, and it settled into a wider variety of positions that could lead to oxidation at several different points along its chain.

The modeling also showed that for both fatty acids, one specific reaction pathway (called ω-1S hydroxylation) required the least energy and was the most likely outcome. However, for EPA specifically, a few alternative pathways were almost equally likely, suggesting the enzyme has more flexibility in how it processes omega-3 fats compared to omega-6 fats. The researchers pinpointed specific enzyme building blocks that seem to control these preferences.