Document Detail


Phytanic acid alpha-oxidation. Differential subcellular localization in rat and human tissues and its inhibition by nycodenz.
MedLine Citation:
PMID:  8486724     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The subcellular site of oxidation of [1-14C]phytanic acid to pristanic acid and CO2 was examined by measurement of the release of 14CO2 in different organelles from human and rat tissues prepared by isopycnic density gradient centrifugation in Nycodenz. The activity of phytanic acid oxidation in human tissues (liver and cultured skin fibroblasts) paralleled that of the peroxisomal marker catalase. We also observed that Nycodenz (commonly used gradient material for isolation of subcellular organelles) has a strong inhibitory effect on the alpha-oxidation of phytanic acid. This inhibition is reversible and can be decreased or eliminated by dialysis of isolated organelles against isotonic solution. The dialysis of endoplasmic reticulum, mitochondrial, and peroxisomal fractions from human liver and cultured skin fibroblasts for 2 h against isotonic solution increased the specific activity of phytanic acid oxidation by 1.3-, 1.3-, and 5-21-fold, respectively, after removal of Nycodenz as compared with nondialyzed samples. After dialysis, the rate of oxidation of phytanic acid in peroxisomes from human liver and cultured skin fibroblasts was 4-26 times higher than that in mitochondria and 43-130 times than that in the endoplasmic reticulum, suggesting that, in human tissues, phytanic acid is oxidized to pristanic acid in peroxisomes. On the other hand, the oxidation of phytanic acid in rat liver paralleled the distribution of the mitochondrial marker cytochrome-c oxidase. The 18-fold higher rate of oxidation in dialyzed mitochondria (198.6 +/- 4.20 pmol/h/mg of protein) than in peroxisomes (11.0 +/- 0.5 pmol/h/mg of protein) demonstrates that, in rodents, phytanic acid is oxidized in mitochondria. 2-[5-(4-Chlorophenyl)pentyl]oxiran-2-carboxylic acid, an inhibitor of carnitine palmitoyltransferase I and mitochondrial fatty acid oxidation, inhibits the oxidation of phytanic acid in rat tissues (liver and cultured skin fibroblasts), whereas it has no effect on the oxidation of phytanic acid in human tissues (liver and cultured skin fibroblasts). The higher specific activity of phytanic acid oxidation in peroxisomes compared with that in mitochondria and the endoplasmic reticulum from human tissues and the inhibition of phytanic acid oxidation by 2-[5-(4-chlorophenyl)pentyl]oxiran-2-carboxylic acid in rat tissues (but not human tissues) demonstrate clearly that, in human tissues, phytanic acid is predominantly oxidized in peroxisomes.
Authors:
I Singh; K Pahan; G S Dhaunsi; O Lazo; P Ozand
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  268     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1993 May 
Date Detail:
Created Date:  1993-06-08     Completed Date:  1993-06-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  9972-9     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Medical University of South Carolina, Charleston 29425.
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MeSH Terms
Descriptor/Qualifier:
Adrenoleukodystrophy / metabolism
Animals
Cell Fractionation / methods
Cells, Cultured
Centrifugation, Density Gradient
Chondrodysplasia Punctata / metabolism
Epoxy Compounds / pharmacology
Fatty Acids / metabolism
Ferric Compounds / pharmacology
Fibroblasts / metabolism
Humans
Hypoglycemic Agents / pharmacology
Iohexol / pharmacology*
Kinetics
Liver / metabolism*
Microbodies / metabolism*
Mitochondria / metabolism
Organelles / drug effects,  metabolism*
Oxidation-Reduction
Palmitic Acid
Palmitic Acids / metabolism
Phytanic Acid / metabolism*
Rats
Rats, Sprague-Dawley
Skin / metabolism*
Subcellular Fractions / metabolism
Zellweger Syndrome / metabolism
Grant Support
ID/Acronym/Agency:
NS-22576/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Epoxy Compounds; 0/Fatty Acids; 0/Ferric Compounds; 0/Hypoglycemic Agents; 0/Palmitic Acids; 14721-66-5/Phytanic Acid; 557-59-5/lignoceric acid; 57-10-3/Palmitic Acid; 66108-95-0/Iohexol; 7705-08-0/ferric chloride; 78573-55-4/ethyl 2-(5-(4-chlorophenyl)pentyl)oxiran-2-carboxylate

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