Alpha oxidation

The α - oxidation is an alternative mechanism for biochemical degradation of fatty acids, which is used, when the normally used β - oxidation is impossible. This is the case when a methylene group at the Cβ the third step, the oxidation to ketone prevented. The name α - oxidation describes that the adjacent to the carboxyl group ( α -position ) carbon atom is oxidized.

Phytanic acid in mammals is degraded as the only fatty acid in this way. This is formed by oxidation of phytol, an alcohol, which is found in esterified form in chlorophyll. Unlike humans ruminants are able to cleave these esters during intestinal transit; on the meat and milk reach about 100 mg per day in the human body. From an energy perspective, the α - oxidation plays only a minor role.

Gradual flow

Activation

Before the dismantling can begin, the acid must be bound to coenzyme A. To provide the necessary energy for the formation of the thioester, pyrophosphate is cleaved by ATP. This reaction catalyzes a Phytanoyl -CoA ligase ( EC 6.2.1.24 ):

Reduction in the peroxisomes

The enzyme peroxisomal Phytanoyl -CoA dioxygenase ( EC 1.14.11.18 ) now oxidizes the α - C atom of phytanic acid in the presence of ascorbic acid and iron with molecular oxygen to alcohol - the second oxygen atom is transferred to 2- oxoglutarate:

2- hydroxyacyl- CoA lyase 1 catalyzes the cleavage in formyl -CoA and Pristanal; Cofactors Mg2 and thiamine pyrophosphate:

Aldehyde, or, more precisely, of its hydrate is cleaved by the enzyme hydrogen Pristanal dehydrogenase and NAD ⁺ transferred to:

Very- long -chain acyl-CoA synthetase enabled again the acid; the energy derived from ATP:

This reaction is necessary to convey the resulting pristanic of peroxisomes back to the cytoplasm - it can be broken down in the mitochondria, by β - oxidation completely to 3 acetyl-CoA, propionyl -CoA and 3 isobutyryl -CoA.

Pathobiochemistry

Are either the enzyme peroxisomal Phytanoyl -CoA dioxygenase, which catalyses the hydroxylation of the Cα, or Peroxin -7, a protein which is transported by this enzyme in the peroxisomes, defective, phytanic acid can not be degraded. Which accumulates in the body and thus causes a syndrome called Refsum disease with severe neurological problems. Permanent cure does not exist, but the symptoms of the disease go through a diet phytansäurearme back.