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 pero ...

to break down dietary

phytanic acid Phytanic acid (or 3,7,11,15-tetramethyl hexadecanoic acid) is a branched chain fatty acid that humans can obtain through the consumption of dairy products, ruminant animal fats, and certain fish. Western diets are estimated to provide 50–100 ...

, 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 (2,6,10,14-tetramethylpentadecanoic acid) is a terpenoid acid present at micromolar concentrations in the blood plasma of healthy individuals. It is also found in the lipids from many sources such as freshwater sponges, krill, earthw ...

. 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

is believed to take place entirely within

. #

Phytanic acid Phytanic acid (or 3,7,11,15-tetramethyl hexadecanoic acid) is a branched chain fatty acid that humans can obtain through the consumption of dairy products, ruminant animal fats, and certain fish. Western diets are estimated to provide 50–100 ...

is first attached to CoA to form phytanoyl-CoA. # Phytanoyl-CoA is oxidized by phytanoyl-CoA dioxygenase, in a process using Fe²⁺ and O₂, to yield 2-hydroxyphytanoyl-CoA. #2-hydroxyphytanoyl-CoA is cleaved by 2-hydroxyphytanoyl-CoA lyase in a TPP-dependent reaction to form pristanal and formyl-CoA (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 ''Ull ...

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 be ...

to form

(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 phytanoyl-CoA dioxygenase) 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). Ref ...

, in which the accumulation of

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 pero ...

biogenesis also prevent alpha-oxidation from occurring.

References

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