Cytochrome P450 omega hydroxylases, also termed cytochrome P450 ω-hydroxylases, CYP450 omega hydroxylases, CYP450 ω-hydroxylases, CYP omega hydroxylase, CYP ω-hydroxylases, fatty acid omega hydroxylases, cytochrome P450 monooxygenases, and fatty acid monooxygenases, are a set of cytochrome P450-containing enzymes that catalyze the addition of a hydroxyl residue to a fatty acid substrate. The CYP omega hydroxylases are often referred to as monoxygenases; however, the monooxygenases are CYP450 enzymes that add a hydroxyl group to a wide range of xenobiotic and naturally occurring endobiotic substrates, most of which are not fatty acids. The CYP450 omega hydroxylases are accordingly better viewed as a subset of monooxygenases that have the ability to hydroxylate fatty acids. While once regarded as functioning mainly in the catabolism of dietary fatty acids, the omega oxygenases are now considered critical in the production or break-down of fatty acid-derived mediators which are made by cells and act within their cells of origin as autocrine signaling agents or on nearby cells as paracrine signaling agents to regulate various functions such as blood pressure control and inflammation.
Action
The omega oxygenases metabolize fatty acids by adding a hydroxyl to their terminal carbons; in the reaction, the two atoms of molecular oxygen by the concomitant oxidation of NADH.
RH + O2 + NADPH + H+ → ROH + H2O + NADP+
Functions
CYP450 enzymes belong to a superfamily which in humans is composed of at least 57 CYPs; within this superfamily, members of six CYP4A subfamilies, possess ω-hydroxylase activity viz., CYP4A, CYP4B, and CYP4F CYP2U1 also possesses ω hydroxylase activity. These CYP ω-hydroxylases can be categorized into several groups based on their substrates and consequential function
1) The only member of the CYP4B subfamily, CYP4B1, shows a preference for ω-oxidizing short-chain fatty acids, i.e. fatty acids that are 7-9 carbons long; CYP4B1 is far more weakly expressed in humans than that expressed in other mammals that were tested. Subsequent to their ω-hydroxylation, these products are converted to their acylcarnitine derivatives and transferred to mitochondria for complete oxidized by beta oxidation.
2) A member of the CYP4A subfamily, CYP4A11, preferentially ω-hydroxylate medium-chain fatty acids, i.e. fatty acids that are 10-16 carbons long; CYP4A11, CYP4F2, CYP4F3A, CYP4F3B, CYP4F11, CYP4V2, and CYP4Z1 also metabolize these fatty acids. Subsequent to their ω-hydroxylation, these products are converted to their acylcarnitine derivatives and transferred to mitochondria for complete oxidized by beta oxidation.
3) Members of the CYP4F family, i.e. CYPA11, CYP4F2, CYP4F3A, CYP4F3B, and CYP4F11, as well as CYP2U1 ω-hydroxylate long chain fatty acids, i.e. fatty acids that are 18 to 20 carbons long. These hydroxyl fatty acids are then serially metabolized by alcohol dehydrogenase, aldehyde dehydrogenase, and dicarboxylyl CoA synthetase to form their respective Coenzyme A -bound dicarboxylic acids and transferred to peroxisomes where they may undergo chain shortening or, as acylcarnitine derivatives or free acids, transferred to mitochondria for complete beta oxidation. The chain-shortened products of peroxisome metabolism may also be converted to phospholipids, triglycerides, and cholesterol esters.
4) Members of the CYP4F family, i.e. CYP4F2 and CYP4F3B, ω-hydroxylate very long chain fatty acids, i.e. fatty acids that are 22 to 26 carbons long. These hydroxyl fatty acids are then serially metabolized by alcohol dehydrogenase, aldehyde dehydrogenase, and dicarboxylyl CoA synthetase to form their respective CoA-bound dicarboxylic acids and transferred to peroxisomes where they may undergo chain shortening or, as acylcarnitine derivatives or free acids, transferred to mitochondria for complete beta oxidation. The chain-shortened products of peroxisome metabolism may also be converted to phospholipids, triglycerides, and cholesterol esters.
