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Journal of Lipid Research, Vol. 41, 629-636, April 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

Phytanoyl-CoA hydroxylase: recognition of 3-methyl-branched acyl-CoAs and requirement for GTP or ATP and Mg²⁺ in addition to its known hydroxylation cofactors

Correspondence to: Paul P. Van Veldhoven

Phytanoyl-CoA hydroxylase is a peroxisomal -oxidation enzyme that catalyzes the 2-hydroxylation of 3-methyl-branched acyl-CoAs. A polyhistidine-tagged human phytanoyl-CoA hydroxylase was expressed in E. coli and subsequently purified as an active protein. The recombinant enzyme required GTP or ATP and Mg²⁺, in addition to its known cofactors Fe²⁺, 2-oxoglutarate, and ascorbate. The enzyme was active towards phytanoyl-CoA and 3-methylhexadecanoyl-CoA, but not towards 3-methylhexadecanoic acid. Racemic, R- and S-3-methylhexadecanoyl-CoA were equally well hydroxylated. Hydroxylation of R- and S-3-methylhexadecanoyl-CoA yielded the (2S,3R) and (2R,3S) isomers of 2-hydroxy-3-methylhexadecanoyl-CoA, respectively. Human phytanoyl-CoA hydroxylase did not show any activity towards 2-methyl- and 4-methyl-branched acyl-CoAs or towards long and very long straight chain acyl-CoAs, excluding a possible role for the enzyme in the formation of 2-hydroxylated and odd-numbered straight chain fatty acids, which are abundantly present in brain.

In conclusion, we report the unexpected requirement for ATP or GTP and Mg²⁺ of phytanoyl-CoA hydroxylase in addition to the known hydroxylation cofactors. Due to the fact that straight chain fatty acyl-CoAs are not a substrate for phytanoyl-CoA hydroxylase, 2-hydroxylation of fatty acids in brain can be allocated to a different enzyme/pathway.—Croes, K., V. Foulon, M. Casteels, P. P. Van Veldhoven, and G. P. Mannaerts. Phytanoyl-CoA hydroxylase: recognition of 3-methyl-branched acyl-CoAs and requirement for GTP or ATP and Mg²⁺ in addition to its known hydroxylation cofactors. J. Lipid Res. 2000. 41: 629;–636.

Supplementary key words: -oxidation, peroxisome, phytanic acid, Refsum's disease, hydroxylation

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