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Alpha oxidation, or α-oxidation, is the name assigned to the enzymatic shortening of fatty acid derivatives that contain a methyl group (CH3-) attached to the carbon atom located beta (β) to the carboxylate group (-COO-). Only one of a series of processes, alpha oxidation involves the metabolizing of specific fatty acids, in the peroxisomes of eukaryotic cells. Inadequate alpha oxidation in the human organism leads to a serious buildup of phytanic acid, which is closely linked to Refsum disease. This genetic disorder is known to produce a host of disturbances, many of them not life-threatening. Most cases of Refsum disease are associated with mutations in the PHYH gene.
Structurally, the original carboxylate is joined to Coenzyme A, and may be drawn ···CH2CH(Me)CH2-COO-(CoA), or phytanoyl-CoA, where the coenzyme’s structure is not written out and the CH3 attached to β-carbon atom is written as “Me” — standing for methyl — to simplify visualization. Identifying the carbon (C) atoms — from right-to-left, not counting the CoA coenzyme carbons — there is the carboxylate-carbon, next the α-carbon, then the β-carbon and the γ-carbon. Carbon atoms to the left of the γ position are excluded for simplification. The biological process requires an enzyme because methyl attached specifically at the beta location hinders metabolism.
In the first step in the multi-step process, a hydrogen atom is replaced with a hydroxyl group (-OH) at the α-carbon. The result is the structure ···CH2CH(Me)CH(OH)-COO-(CoA). Next follows decarboxylation, coupled with oxidation, to give ···CH2CH(Me)-COO-(CoA). Following alpha oxidation is another metabolic step called beta oxidation. Unfortunately, failure in the alpha oxidation process is not covered by this latter process — phytanic acid is not metabolized by means of beta oxidation or any other fatty acid metabolic process.
Since Refsum disease closely relates to an excess of phytanic acid, and phytanic acid comes directly from the diet, a large part of an individual’s treatment has to do with diet. It is found specifically in dairy products, beef, lamb, and certain fish — including tuna, cod and haddock. For some individuals, a difficult and costly blood filtration procedure called plasmapheresis may be used. The lesser itchy skin and muscular degeneration issues can be resolved with treatment, and one day it is hoped that enzymatic treatment may reduce phytanic acid buildup, and with it Refsum’s more serious issues. At present, however, the outcome can be as serious as death resulting from heart arrythmia.
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