Enzymatic steps of alpha oxidation, 250px Alpha oxidation (α-oxidation) is a process by which certain branched-chain

fatty acids In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...

are broken down by removal of a single carbon from the carboxyl end. In humans, alpha-oxidation is used in

peroxisomes A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen pe ...

to break down dietary phytanic acid, which cannot undergo

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 cycle ...

due to its β-methyl branch, into pristanic acid. Pristanic acid can then acquire acetyl-CoA and subsequently become beta oxidized, yielding

propionyl-CoA Propionyl-CoA is a coenzyme A derivative of propionic acid. It is composed of a 24 total carbon chain (without the coenzyme, it is a 3 carbon structure) and its production and metabolic fate depend on which organism it is present in. Several diffe ...

Pathway

Alpha-oxidation of phytanic acid is believed to take place entirely within

. # Phytanic acid is first attached to

CoA Coa may refer to: Places * Coa, County Fermanagh, a rural community in County Fermanagh, Northern Ireland * Côa River, a tributary of the Douro, Portugal ** Battle of Coa, part of the Peninsular War period of the Napoleonic Wars ** Côa Vall ...

to form

phytanoyl-CoA Phytanoyl-CoA is a derivative of phytanic acid. See also * Phytanoyl-CoA hydroxylase {{Peroxisomal metabolism intermediates Thioesters of coenzyme A ...

. #

Phytanoyl-CoA Phytanoyl-CoA is a derivative of phytanic acid. See also * Phytanoyl-CoA hydroxylase {{Peroxisomal metabolism intermediates Thioesters of coenzyme A ...

is oxidized by

phytanoyl-CoA dioxygenase In enzymology, a phytanoyl-CoA dioxygenase () is an enzyme that catalyzes the chemical reaction :phytanoyl-CoA + 2-oxoglutarate + O2 \rightleftharpoons 2-hydroxyphytanoyl-CoA + succinate + CO2 The three substrates of this enzyme are phytano ...

, in a process using Fe²⁺ and O₂, to yield 2-hydroxyphytanoyl-CoA. #2-hydroxyphytanoyl-CoA is cleaved by

2-hydroxyphytanoyl-CoA lyase 2-Hydroxyphytanoyl-CoA lyase is a peroxisomal enzyme involved in the catabolism of phytanoic acid by α-oxidation. It requires thiamine diphosphate Thiamine pyrophosphate (TPP or ThPP), or thiamine diphosphate (ThDP), or cocarboxylase is a thi ...

in a TPP-dependent reaction to form pristanal and

formyl-CoA Acyl-CoA is a group of coenzymes that metabolize fatty acids. Acyl-CoA's are susceptible to beta oxidation, forming, ultimately, acetyl-CoA. The acetyl-CoA enters the citric acid cycle, eventually forming several equivalents of ATP. In this way ...

(in turn later broken down into

formate Formate ( IUPAC name: methanoate) is the conjugate base of formic acid. Formate is an anion () or its derivatives such as ester of formic acid. The salts and esters are generally colorless.Werner Reutemann and Heinz Kieczka "Formic Acid" in ...

and eventually CO₂). #Pristanal is oxidized by

aldehyde dehydrogenase Aldehyde dehydrogenases () are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes (R–C(=O)) to carboxylic acids (R–C(=O)). The oxygen comes from a water molecule. To date, nineteen ALDH genes have b ...

to form pristanic acid (which can then undergo

). (Propionyl-CoA is released as a result of beta oxidation when the beta carbon is substituted)

Deficiency

Enzymatic deficiency in alpha-oxidation (most frequently in

) leads to

Refsum's disease Refsum disease is an autosomal recessive neurological disease that results in the over-accumulation of phytanic acid in cells and tissues. It is one of several disorders named after Norwegian neurologist Sigvald Bernhard Refsum (1907–1991). R ...

, in which the accumulation of phytanic acid and its derivatives leads to neurological damage. Other disorders of

peroxisome A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen ...

biogenesis also prevent alpha-oxidation from occurring.

References

# # {{Lipid metabolism enzymes Biochemistry Cell biology Metabolic pathways Fatty acids