The metabolism of phytanic acid and pristanic acid in man: A review

  title={The metabolism of phytanic acid and pristanic acid in man: A review},
  author={Nanda M. Verhoeven and Ronald J.A. Wanders and Bwee Tien Poll-The and Jean Marie Saudubray and Cornelis Jakobs},
  journal={Journal of Inherited Metabolic Disease},
The branched-chain fatty acid phytanic acid is a constituent of the diet, present in diary products, meat and fish. Degradation of this fatty acid in the human body is preceded by activation to phytanoyl-CoA and starts withone cycle of α-oxidation. Intermediates in this pathway are 2-hydroxy-phytanoyl-CoA and pristanal; the product is pristanic acid. After activation, pristanic acid is degraded by peroxisomal β-oxidation. Several disorders havebeen described in which phytanic acid accumulates… 
Phytanic acid α-oxidation in man: Identification of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal enzyme with normal activity in Zellweger syndrome
Recent studies have shown that 2-hydroxyphytanoyl-CoA lyase is a peroxisomal enzyme, at least in the rat, like phytanoyl -CoA, and pristanal is converted into pristanic acid via an aldehyde dehydrogenase.
Phytanic acid: production from phytol, its breakdown and role in human disease
This review will centre on this research on phytanic acid: its origin, the mechanism by which its α-oxidation takes place, its role in human disease and the way it is produced from phytol.
Phytanic acid – a tetramethyl-branched fatty acid in food
Phytanic acid is a tetramethyl-branched isoprenoid fatty acid. Its presence in food is linked with chlorophyll, which contains its precursor, i. e. the alcohol side-chain phytol. The bioconversion of
In brain mitochondria the branched-chain fatty acid phytanic acid impairs energy transduction and sensitizes for permeability transition.
In neural tissue, which becomes enriched with phytanic acid, the reduction in mitochondrial ATP supply and the facilitation of the opening of the permeability transition pore are two major mechanisms by which the branched-chain fatty acid phytic acid induces the onset of degenerative processes.
Pristanic acid and phytanic acid: naturally occurring ligands for the nuclear receptor peroxisome proliferator-activated receptor alpha.
It is demonstrated that both pristanic acid and phytanic acid are naturally occurring ligands for PPARalpha, which are present at physiological concentrations.
Phytol-induced Hepatotoxicity in Mice
The results suggest that phytol may cause selective midzonal hepatocellular necrosis in mice, an uncommon pattern of hepatotoxic injury, and that the greater susceptibility of female mice may reflect a lower capacity to oxidize phytanic acid because of their intrinsically lower hepatic expression of SCP-x.
Metabolism of phytol to phytanic acid in the mouse, and the role of PPARalpha in its regulation.
The results described here show that the conversion of phytol to phytanic acid is regulated via PPARalpha and is specific for the breakdown of (E)-phytol.


Evidence against α-hydroxyphytanic acid as an intermediate in the metabolism of phytanic acid
It is shown that when cultured skin fibroblasts from both groups of patients as well as from healthy controls are incubated with (1-14C)phytanic acid, the only radioactive compounds which can be detected are 14CO2 and unmetabolised phytanic acid.
Phytanic acid must be activated to phytanoyl-CoA prior to its alpha-oxidation in rat liver peroxisomes.
Accumulation of pristanic acid (2, 6, 10, 14 tetramethylpentadecanoic acid) in the plasma of patients with generalised peroxisomal dysfunction
The plasma of some patients with biochemical evidence of a generalised peroxisomal dysfunction (GPD) show greatly increased levels of phytanic acid as well as its α-oxidation product, pristanic acid, which indicates that a number of the steps in phytic acid degradation may be confined to peroxISomes.
Alpha-oxidation of Fatty Acids in Various Mammals, and a Phytanic Acid Feeding Experiment in an Animal with a Low Alpha-oxidation Capacity
Patients with Refsum's disease, who accumulate phytanic acid, have a reduced capacity for α-oxidation of branched chain fatty acids. To try to elucidate the role of phytanic acid in the
Resolution of the phytanic acid alpha-oxidation pathway: identification of pristanal as product of the decarboxylation of 2-hydroxyphytanoyl-CoA.
The results show that pristanal is formed from 2-hydroxyphytanoyl-CoA, which is subsequently oxidized to pristanic acid in a NAD+ dependent reaction and resolved the mechanism of the phytanic acid alpha-oxidation process in human liver.
Identification of pristanoyl-CoA oxidase and phytanic acid decarboxylation in peroxisomes and mitochondria from human liver: Implications for Zellweger syndrome
The results suggest that phytanic acid decarboxylation takes place in mitochondria, whereas-oxidation of pristanic acid is likely to be carried out in peroxisomes.
Phytanic acid and pristanic acid are oxidized by sequential peroxisomal and mitochondrial reactions in cultured fibroblasts.
It is demonstrated that both phytanic acid and pristanic acid are initially oxidized in peroxisomes to 4,8-dimethylnonanoyl-CoA, which is converted to the corresponding acylcarnitine, and exported to the mitochondrion.
Phytanoyl-CoA hydroxylase is present in human liver, located in peroxisomes, and deficient in Zellweger syndrome: direct, unequivocal evidence for the new, revised pathway of phytanic acid alpha-oxidation in humans.
It is suggested that phytanic acid alpha-oxidation is peroxisomal and that it utilizes the coenzyme A derivative as substrate, thus giving further support in favour of the new, revised pathway of phytanoyl-CoA alpha-Oxidation.
Phytanic acid alpha-oxidation: decarboxylation of 2-hydroxyphytanoyl-CoA to pristanic acid in human liver.
The degradation of the first intermediate in the alpha-oxidation of phytanic acid, 2-hydroxyphytanoyl-CoA, was investigated and suggested the existence of two pathways for decarboxylation of 2-Hydroxyphytanic acid.
Studies on the alpha oxidation of phytanic acid by rat liver mitochondria.
The proposed mechanism of mammalian catabolism of phytanic acid involves initial α oxidation leading through α-hydroxyphytanic acid to pristanic acid, and subsequent β oxidations, and the addition of Fe+++ ions greatly stimulates this reaction.