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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS021321-01A2
Application #
3402332
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1986-08-01
Project End
1989-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Medical College of Georgia (MCG)
Department
Type
Schools of Medicine
DUNS #
City
Augusta
State
GA
Country
United States
Zip Code
30912
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Carroll, J E; Carter, A L; Perlman, S (1987) Carnitine deficiency revisited. J Nutr 117:1501-3
Knigge, K M; Piekut, D T; Joseph, S A (1985) The alpha MSH-specific and arcuate pro-opiomelanocortin neuronal systems of the hypothalamus: observations on their connectivity and response to colchicine treatment. Psychopharmacol Bull 21:472-5