Tags

Type your tag names separated by a space and hit enter

Phytanic acid alpha-oxidation in rat liver peroxisomes. Production of alpha-hydroxyphytanoyl-CoA and formate is enhanced by dioxygenase cofactors.
Eur J Biochem. 1995 Sep 01; 232(2):545-51.EJ

Abstract

Patients with generalized peroxisomal disorders, rhizomelic chondrodysplasia punctata, and Refsum disease are all unable to alpha-oxidize 3,7,11,15-tetramethylhexadecanoic (phytanic) acid. The exact cause of the oxidation defect in these patients is not well characterized, in part because there is only limited knowledge of the biochemical pathway. In 1969, the alpha-oxidation of phytanic acid was reported [Tsai, S.-C., Avigan, J. & Steinberg, D. (1969) Studies on the alpha-oxidation of phytanic acid by rat liver mitochondria, J. Biol. Chem. 244, 2682-2692] to involve the formation of an alpha-hydroxyphytanic acid intermediate prior to removal of the alpha carbon. Subsequently, most researchers have had difficulty detecting this intermediate. In the present study, cofactors known to form hydroxy intermediates by both monooxygenase and dioxygenase reaction mechanisms were incubated with purified rat liver peroxisomes and either [2,3-3H]phytanic acid or [1-14C]phytanic acid. Reaction products were separated by reverse-phase HPLC. A single reaction product, identified as alpha-hydroxyphytanoyl-CoA rather than the free fatty acid, was detected when 2-oxoglutarate/Fe+2/ascorbate, cofactors associated with a dioxygenase reaction mechanism, were present. Concomitant with alpha-hydroxyphytanoyl-CoA production, there was an increased accumulation of formate and CO2. This increase in alpha-oxidation products is evidence that alpha-hydroxyphytanoyl-CoA is a true pathway intermediate and that the entire pathway functions in peroxisomes. In contrast, alpha-hydroxyphytanoyl-CoA was not formed in any quantity in mitochondria. These studies suggest that the alpha-hydroxylation step of phytanic acid oxidation, which has been shown to be defective in Refsum disease, is located in peroxisomes.

Authors+Show Affiliations

Kennedy Krieger Research Institute, John Hopkins University School of Medicine, Baltimore, MD 21205, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7556205

Citation

Mihalik, S J., et al. "Phytanic Acid Alpha-oxidation in Rat Liver Peroxisomes. Production of alpha-hydroxyphytanoyl-CoA and Formate Is Enhanced By Dioxygenase Cofactors." European Journal of Biochemistry, vol. 232, no. 2, 1995, pp. 545-51.
Mihalik SJ, Rainville AM, Watkins PA. Phytanic acid alpha-oxidation in rat liver peroxisomes. Production of alpha-hydroxyphytanoyl-CoA and formate is enhanced by dioxygenase cofactors. Eur J Biochem. 1995;232(2):545-51.
Mihalik, S. J., Rainville, A. M., & Watkins, P. A. (1995). Phytanic acid alpha-oxidation in rat liver peroxisomes. Production of alpha-hydroxyphytanoyl-CoA and formate is enhanced by dioxygenase cofactors. European Journal of Biochemistry, 232(2), 545-51.
Mihalik SJ, Rainville AM, Watkins PA. Phytanic Acid Alpha-oxidation in Rat Liver Peroxisomes. Production of alpha-hydroxyphytanoyl-CoA and Formate Is Enhanced By Dioxygenase Cofactors. Eur J Biochem. 1995 Sep 1;232(2):545-51. PubMed PMID: 7556205.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phytanic acid alpha-oxidation in rat liver peroxisomes. Production of alpha-hydroxyphytanoyl-CoA and formate is enhanced by dioxygenase cofactors. AU - Mihalik,S J, AU - Rainville,A M, AU - Watkins,P A, PY - 1995/9/1/pubmed PY - 1995/9/1/medline PY - 1995/9/1/entrez SP - 545 EP - 51 JF - European journal of biochemistry JO - Eur J Biochem VL - 232 IS - 2 N2 - Patients with generalized peroxisomal disorders, rhizomelic chondrodysplasia punctata, and Refsum disease are all unable to alpha-oxidize 3,7,11,15-tetramethylhexadecanoic (phytanic) acid. The exact cause of the oxidation defect in these patients is not well characterized, in part because there is only limited knowledge of the biochemical pathway. In 1969, the alpha-oxidation of phytanic acid was reported [Tsai, S.-C., Avigan, J. & Steinberg, D. (1969) Studies on the alpha-oxidation of phytanic acid by rat liver mitochondria, J. Biol. Chem. 244, 2682-2692] to involve the formation of an alpha-hydroxyphytanic acid intermediate prior to removal of the alpha carbon. Subsequently, most researchers have had difficulty detecting this intermediate. In the present study, cofactors known to form hydroxy intermediates by both monooxygenase and dioxygenase reaction mechanisms were incubated with purified rat liver peroxisomes and either [2,3-3H]phytanic acid or [1-14C]phytanic acid. Reaction products were separated by reverse-phase HPLC. A single reaction product, identified as alpha-hydroxyphytanoyl-CoA rather than the free fatty acid, was detected when 2-oxoglutarate/Fe+2/ascorbate, cofactors associated with a dioxygenase reaction mechanism, were present. Concomitant with alpha-hydroxyphytanoyl-CoA production, there was an increased accumulation of formate and CO2. This increase in alpha-oxidation products is evidence that alpha-hydroxyphytanoyl-CoA is a true pathway intermediate and that the entire pathway functions in peroxisomes. In contrast, alpha-hydroxyphytanoyl-CoA was not formed in any quantity in mitochondria. These studies suggest that the alpha-hydroxylation step of phytanic acid oxidation, which has been shown to be defective in Refsum disease, is located in peroxisomes. SN - 0014-2956 UR - https://www.unboundmedicine.com/medline/citation/7556205/Phytanic_acid_alpha_oxidation_in_rat_liver_peroxisomes__Production_of_alpha_hydroxyphytanoyl_CoA_and_formate_is_enhanced_by_dioxygenase_cofactors_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0014-2956&date=1995&volume=232&issue=2&spage=545 DB - PRIME DP - Unbound Medicine ER -