Omega oxidation (ω-oxidation) is a process of fatty acid metabolism in some species of animals. It is an alternative pathway to

beta oxidation In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cyc ...

that, instead of involving the β carbon, involves the oxidation of the ω carbon (the carbon most distant from the

carboxyl group In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...

of the fatty acid). The process is normally a minor catabolic pathway for medium-chain fatty acids (10-12 carbon atoms), but becomes more important when β oxidation is defective. In vertebrates, the enzymes for ω oxidation are located in the

smooth ER The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

and

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...

cells, instead of in the mitochondria as with β oxidation. The steps of the process are as follows: After these three steps, either end of the fatty acid can be attached to coenzyme A. The molecule can then enter the mitochondrion and undergo β oxidation. The final products after successive oxidations include

succinic acid Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. The name derives from Latin ''succinum'', meaning amber. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological ro ...

, which can enter the

citric acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and protein ...

, and

adipic acid Adipic acid or hexanedioic acid is the organic compound with the formula (CH2)4(COOH)2. From an industrial perspective, it is the most important dicarboxylic acid: about 2.5 billion kilograms of this white crystalline powder are produced annuall ...

. The first step in ω-oxidation, i.e. addition of a hydroxy residue to the omega carbon of short, intermediate, and long chain unsaturated or saturated fatty acids, can serve to produce or inactivate signaling molecules. In humans, a subset of

Cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...

(CYP450)

microsome In cell biology, microsomes are heterogeneous vesicle-like artifacts (~20-200 nm diameter) re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, liv ...

-bound ω-hydroxylases (termed

Cytochrome P450 omega hydroxylase 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 ...

s) metabolize arachidonic acid (also known as eicosatetraenoic acid) to 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE possesses a range of activities in animal and cellular model systems, e.g. it constricts blood vessels, alters the kidney's reabsorption of salt and water, and promotes the growth of cancer cells; genetic studies in humans suggest that 20-HETE contributes to hypertension,

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...

, and brain stroke (see 20-Hydroxyeicosatetraenoic acid). Among the CYP450 superfamily, members of the CYP4A and CYP4F subfamilies viz.,

CYP4A11 Cytochrome P450 4A11 is a protein that in humans is codified by the ''CYP4A11'' gene. Function This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reacti ...

CYP4F2 Leukotriene-B(4) omega-hydroxylase 1 is an enzyme protein involved in the metabolism of various endogenous substrates (mainly the fatty acids) and xenobiotics (including pharmaceutical drugs). The most notable substrate of the enzyme is leukotrie ...

, CYP4F3, are considered the predominant cytochrome P450 enzymes responsible in most tissues for forming 20-HETE.

CYP2U1 CYP2U1 (cytochrome P450, family 2, subfamily U, polypeptide 1) is a protein that in humans is encoded by the ''CYP2U1'' gene Function This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are m ...

and CYP4Z1 contribute to 20-HETE production in a more limited range of tissues. The cytochrome ω-oxidases including those belonging to the CYP4A and CYP4F sub-families and CYPU21 also ω-hydroxylate and thereby reduce the activity of various fatty acid metabolites of arachidonic acid including

LTB4 Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It has been shown to promote insulin resistance in obese mice. Biochemistry Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It is produced from leukocytes in respon ...

, 5-HETE, 5-oxo-eicosatetraenoic acid, 12-HETE, and several

prostaglandins The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are deriv ...

that are involved in regulating various inflammatory, vascular, and other responses in animals and humans. This hydroxylation-induced inactivation may underlie the proposed roles of the cytochromes in dampening inflammatory responses and the reported associations of certain CYP4F2 and CYP4F3

single nucleotide variant In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...

s with human Crohn's disease and

Celiac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...

, respectively.

References

*Nelson, D. L. & Cox, M. M. (2005). ''Lehninger Principles of Biochemistry'', 4th Edition. New York: W. H. Freeman and Company, pp. 648–649. {{ISBN, 0-7167-4339-6.

External links

* http://www.biocarta.com/pathfiles/omegaoxidationPathway.asp Organic redox reactions

See also

References

External links