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 α-oxidation in humans

G. A. Jansen, S. J. Mihalik, Paul A Watkins, H. W. Moser, C. Jakobs, S. Denis, R. J A Wanders

Research output: Contribution to journalArticle

Abstract

Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a branched-chain fatty acid which accumulates in a number of inherited diseases in human. Because β-oxidation is blocked by the methyl group at C-3, phytanic acid first undergoes decarboxylation via an α-oxidation mechanism. The structure and subcellular localization of the phytanic acid α-oxidation pathway have remained enigmatic through the years, although they have generally been assumed to involve phytanic acid and not its CoA-ester. This view has recently been challenged by the findings that in rat liver phytanic acid first has to be activated to its CoA-ester before α-oxidation and by the discovery of a new enzyme, phytanoyl-CoA hydroxylase, which converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA. We now show that this newly discovered enzyme is also present in human liver. Furthermore, we show that this enzyme is located in peroxisomes and deficient in liver from Zellweger patients who lack morphologically distinguishable peroxisomes, which provides an explanation for the long-known deficient oxidation of phytanic acid in these patients. These results suggest that phytanic acid α-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 phytanic acid α-oxidation.

Original languageEnglish (US)
Pages (from-to)205-210
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume229
Issue number1
DOIs
StatePublished - Dec 4 1996

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Phytanic Acid
Zellweger Syndrome
Peroxisomes
Mixed Function Oxygenases
Liver
Oxidation
Coenzyme A
Esters
Enzymes
Decarboxylation
phytanoyl-coenzyme A
Rats
Fatty Acids
Derivatives

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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title = "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 α-oxidation in humans",
abstract = "Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a branched-chain fatty acid which accumulates in a number of inherited diseases in human. Because β-oxidation is blocked by the methyl group at C-3, phytanic acid first undergoes decarboxylation via an α-oxidation mechanism. The structure and subcellular localization of the phytanic acid α-oxidation pathway have remained enigmatic through the years, although they have generally been assumed to involve phytanic acid and not its CoA-ester. This view has recently been challenged by the findings that in rat liver phytanic acid first has to be activated to its CoA-ester before α-oxidation and by the discovery of a new enzyme, phytanoyl-CoA hydroxylase, which converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA. We now show that this newly discovered enzyme is also present in human liver. Furthermore, we show that this enzyme is located in peroxisomes and deficient in liver from Zellweger patients who lack morphologically distinguishable peroxisomes, which provides an explanation for the long-known deficient oxidation of phytanic acid in these patients. These results suggest that phytanic acid α-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 phytanic acid α-oxidation.",
author = "Jansen, {G. A.} and Mihalik, {S. J.} and Watkins, {Paul A} and Moser, {H. W.} and C. Jakobs and S. Denis and Wanders, {R. J A}",
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T2 - Direct, unequivocal evidence for the new, revised pathway of phytanic acid α-oxidation in humans

AU - Jansen, G. A.

AU - Mihalik, S. J.

AU - Watkins, Paul A

AU - Moser, H. W.

AU - Jakobs, C.

AU - Denis, S.

AU - Wanders, R. J A

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