Project: Research project

Project Details


The objective of this proposal is to elucidate biochemical causes of muscle
fatty acid oxidation defects in humans. Patients singled out for
investigation will include those having increased fatty acid intermediary
oxidation metabolites of CoA or carnitine or abnormal in vitro oxidation of
1-14C or U-14C-palmitate. Patients of particular interest will be those
with the various dystrophies, since we have alrady determined that these
subjects not only accumulate fatty acid intermediary metabolites, but also
demonstrate defective oxidation of U-14C-palmitate. This finding suggests
that the abnormality lies after the oxidation of the first carbon.

Chain length specific acyl-CoA dehydrogenase (AD) proteins, the first step
in intramitochondrial Beta-oxidation, will be studied in skeletal muscle of
these patients and control subjects using an enzyme activity-based staining
technique with polyacrylamide gel electrophoresis and also high performance
liquid chromatography.

Chain length specific enoyl-CoA hydratase and 3-ketoacyl-CoA thiolase
activities will be studied in the same patients using appropriate long and
short chain CoA derivates.

These methods should allow localization of the intramitochondrial
beta-oxidation defects in chain length specific enzymes.
StatusNot started