Omega oxidation (ω-oxidation) is a process of

fatty acid metabolism Fatty acid metabolism consists of various metabolic processes involving or closely related to fatty acids, a family of molecules classified within the lipid macronutrient category. These processes can mainly be divided into (1) catabolic processe ...

in some species of animals. It is an alternative pathway to

beta oxidation In biochemistry and metabolism, beta oxidation (also β-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. Acetyl-CoA enter ...

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 often written as or , sometimes as with R referring to an organyl group (e.g. ...

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 An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...

for ω oxidation are located in the smooth ER of

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

and

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

cells, instead of in the

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

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 Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the Fatty acid metabolism#Synthesis, synthesis and Fatty acid metabolism#.CE.B2-Oxidation, oxidation of fatty acids, and the oxidation of pyruvic acid, pyruvate in the citric ac ...

. 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. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into fum ...

, which can enter the

citric acid cycle The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of chemical reaction, biochemical reactions that release the energy stored in nutrients through acetyl-Co ...

, and

adipic acid Adipic acid or hexanedioic acid is the organic compound with the formula C6H10O4. It a white crystalline powder at standard temperature and pressure. From an industrial perspective, it is the most important dicarboxylic acid at about 2.5 billion ...

. 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 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

(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, l ...

-bound ω-hydroxylases (termed Cytochrome P450 omega hydroxylases) metabolize

arachidonic acid Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega−6 fatty acid 20:4(ω−6), or 20:4(5,8,11,14). It is a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes. Together with omega−3 fatty acids an ...

(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 Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

, and brain

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

(see 20-Hydroxyeicosatetraenoic acid). Among the CYP450 superfamily, members of the CYP4A and CYP4F subfamilies viz., CYP4A11, CYP4F2, CYP4F3, are considered the predominant cytochrome P450 enzymes responsible in most tissues for forming 20-HETE. CYP2U1 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,

5-HETE 5-Hydroxyeicosatetraenoic acid (5-HETE, 5(''S'')-HETE, or 5''S''-HETE) is an eicosanoid, i.e. a metabolite of arachidonic acid. It is produced by diverse cell types in humans and other animal species. These cells may then metabolize the formed 5(' ...

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

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

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 variants with human

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...

and

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

, 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 Biochemical reactions Lipid metabolism Organic redox reactions

See also

References

External links