Effects of odd-numbered medium-chain fatty acids on the accumulation of long-chain 3-hydroxy-fatty acids in long-chain L-3-hydroxyacyl CoA dehydrogenase and mitochondrial trifunctional protein deficient skin fibroblasts.
The treatment for patients with genetic disorders of mitochondrial long-chain fatty acid beta-oxidation is directed toward providing sufficient sources of energy for normal growth and development, and at the same time preventing the adverse effects that precipitate or result from metabolic decompensation. Standard of care treatment has focused on preventing the mobilization of lipids that result from fasting and providing medium-chain triglycerides (MCT) in the diet in order to bypass the long-chain metabolic block. MCTs that are currently available as commercial preparations are in the form of even-chain fatty acids that are predominately a mixture of octanoate and decanoate. Recently, the use of odd-chain fatty acids has been proposed as an alternative treatment. We have shown previously that the even-numbered medium-chain fatty acids (MCFAs) that are found in MCT preparations can reduce the accumulation of potentially toxic long-chain metabolites of fatty acid oxidation (FAO). In the current study, we undertook to determine if the same is true of odd-numbered MCFAs. We found that provision of odd-chain species does decrease the build-up of long-chain FAO intermediates in our in vitro skin fibroblast model, but to a lesser extent than even-numbered MCFAs.
Jones
Patricia M
PM
Department of Pathology, University of Texas Southwestern Medical Center, Children's Medical Center of Dallas, Dallas, TX 75235, USA. patricia.jones@utsouthwestern.edu
Butt
Yasmeen M
YM
Bennett
Michael J
MJ
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency* / Q000378:metabolism; D002210:Caprylates / Q000378:metabolism; D002460:Cell Line; D003470:Culture Media; D003651:Decanoates / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D006537:Heptanoates / Q000378:metabolism; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000178:diet therapy / Q000235:genetics / Q000378:metabolism*; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D028361:Mitochondrial Diseases / Q000178:diet therapy / Q000378:metabolism*; D012867:Skin / Q000166:cytology
D002210:Caprylates; D003470:Culture Media; D003651:Decanoates; D005227:Fatty Acids; D006537:Heptanoates; C008776:pelargonic acid; D015094:3-Hydroxyacyl CoA Dehydrogenases; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase