Alpha and Omega oxidation: Fatty acid oxidation Part III

@vips biochemistry

Alpha oxidation: Oxidation occur at carbon 2 and not at carbon 3 as happens in beta oxidation
Omega Oxidation: Oxidation occurs at the methyl end of fatty acid which is the omega carbon

Alpha Oxidation: it was first observed in seed and leaf tissues in plants and in humans it takes place in endoplasmic reticulum and microsomes of brain and liver. The process basically involves the removal of the terminal carbon from the carboxyl end as CO2 and the remaining odd chain fatty acid is subjected to beta oxidation to produce energy.
Prior activation is not required in the alpha oxidation step here. so no involvement of CoA in this event.
Phytanic acid, a 20 carbon branched chain fatty acid is taken as the best example for demonstrating alpha oxidation. Phytanic acid is formed from the phytol tail in chlorophyll and side chain of vitamin K2, as well as present in milk and animal fats, through which it enters our body by direct absorption.
Direct beta oxidation is not possible in Phytanic acid, since it is having a methyl group attached to the third carbon which is termed as the beta carbon in fatty acids.
The process involves hydroxylation of the original alpha carbon followed by Decarboxylation at that position.The final products can be channeled to beta oxidation after activating with CoA., to form propionyl CoA and acetyl CoA. Propionyl CoA can be converted to succinyl CoA also and be taken to TCA cycle.Phytanate alpha- oxidase deficiency can lead to the accumulation of Phytanic acid in plasma and tissues which give rise to a condition called Refsum’s disease.

Omega Oxidation: Occurs in the endoplasmic reticulum of many tissues. Occurs in medium chain fatty acids only like for example, lauric acid a 12 carbon fatty acid, which is taken as an example to illustrate omega oxidation here. The process Involves hydroxylation followed by oxidation of ω-carbon. The enzyme involved is a “mixed function” oxidase requiring cytochrome P450, Oxygen and NADPH. Here, what we mean by Mixed function oxidase is that it’s a complex enzyme that catalyse a reaction in which each of the two atoms of oxygen is used for separate, different functions in the same reaction.
Further alcohol dehydrogenase and then aldehyde dehydrogenase are involved in sequential manner. Actually what happens is that a fatty alcohol and then a fatty aldehyde is formed which give rise to a dicarboxylic fatty acid at the end. A dicarboxylic acid with COOH groups at both ends is formed.
This product can undergo beta oxidation. In this molecule, either of the carboxylic acid groups can be activated with CoA, but not both ends. beta oxidation releases acetyl CoA as usually happens and finally gives rise to shorter chain fatty acids like Adipic acid (6C). Adipic acid may further undergo one more beta oxidation to give (4C) succinic acid or it can take its own route of metabolism. Succinate is familiar to us, being the intermediate substrate of TCA cycle and so it can enter TCA and lead to ATP synthesis.
This pathway is generally not the major route for oxidative catabolism of fatty acids, and actually is a minor pathway and may help remove toxic levels of fatty acids during pathological conditions like diabetes or chronic alcoholism.