Medium-chain fatty acids undergo elongation before beta-oxidation in fibroblasts.
Although mitochondrial fatty acid beta-oxidation (FAO) is considered to be well understood, further elucidation of the pathway continues through evaluation of patients with FAO defects. The FAO pathway can be examined by measuring the 3-hydroxy-fatty acid (3-OHFA) intermediates. We present a unique finding in the study of this pathway: the addition of medium-chain fatty acids to the culture media of fibroblasts results in generation of 3-OHFAs which are two carbons longer than the precursor substrate. Cultured skin fibroblasts from normal and LCHAD-deficient individuals were grown in media supplemented with various chain-length fatty acids. The cell-free medium was analyzed for 3-OHFAs by stable-isotope dilution gas-chromatography/mass-spectrometry. Our finding suggests that a novel carbon chain-length elongation process precedes the oxidation of medium-chain fatty acids. This previously undescribed metabolic step may have important implications for the metabolism of medium-chain triglycerides, components in the dietary treatment of a number of disorders.
Jones
Patricia M
PM
Department of Pathology, University of Texas Southwestern Medical Center, Dalls, TX 75235, USA. Patti.Jones@childrens.com
Butt
Yasmeen
Y
Messmer
Bette
B
Boriak
Richard
R
Bennett
Michael J
MJ
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000102:Acetyl-CoA C-Acyltransferase / Q000378:metabolism; D000123:Acetyltransferases / Q000378:metabolism; D002210:Caprylates / Q000378:metabolism; D019748:Carbon-Carbon Double Bond Isomerases / Q000378:metabolism; D002460:Cell Line; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007848:Laurates / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism; D019998:Racemases and Epimerases / Q000378:metabolism
D002210:Caprylates; D005227:Fatty Acids; D007848:Laurates; C038784:fatty acid oxidation complex; D019308:Palmitic Acid; D015094:3-Hydroxyacyl CoA Dehydrogenases; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D000102:Acetyl-CoA C-Acyltransferase; D004746:Enoyl-CoA Hydratase; D019998:Racemases and Epimerases; D019748:Carbon-Carbon Double Bond Isomerases; C031492:octanoic acid