Palmitic acid-1-14C oxidation by skeletal muscle mitochondria of dystrophic mice

1970 ◽  
Vol 48 (5) ◽  
pp. 566-572 ◽  
Author(s):  
C. H. Lin ◽  
A. J. Hudson ◽  
K. P. Strickland

Cofactor requirements for the oxidation of palmitate-1-14C by 600 × g supernatant fraction of mouse skeletal muscle homogenate and by skeletal muscle mitochondria are described. Optimal oxidation of palmitate-1-14C by skeletal muscle mitochondria requires the presence of carnitine, ATP, CoA, and a Krebs cycle intermediate (e.g. succinate). Succinate, malate, alpha-ketoglutarate, and oxaloacetate are all equally effective in supporting the oxidation, but isocitrate is less effective. The oxidation of palmitate-1-14C by 600 × g supernatant fraction of muscle homogenate as well as by skeletal muscle mitochondria from dystrophic mice is significantly decreased compared with that of the normal littermate controls. The present results, together with the previous findings, suggest that the decrease in oxidation of palmitate-1-14C by the dystrophic muscle preparations is most likely due to a defect in one or more of the steps of the Krebs cycle.

1972 ◽  
Vol 50 (7) ◽  
pp. 749-754 ◽  
Author(s):  
J. J. Jato-Rodriguez ◽  
C. H. Lin ◽  
A. J. Hudson ◽  
K. P. Strickland

Mitochondria isolated from the hind leg muscle of normal and dystrophic mice (strain 129) were compared in their capacity to oxidize acetyl-1-14C-l-carnitine. Oxidation in the mitochondria from dystrophic animals was reduced by 80%. Carnitine acetyltransferase (EC 2.3.1.7) activity in the mitochondria was determined and showed a 35% reduction in the mitochondria from dystrophic muscle. A larger decrease (55%) was observed in the mitochondrial content of acid-soluble CoA. Although the combined decreases in carnitine acetyltransferase and CoA can largely account for the observed decrease in acetylcarnitine oxidation in the mitochondria isolated from dystrophic muscle, it is conceivable that some defect may still exist in the utilization of acetyl groups in the tricarboxylic acid cycle.


1980 ◽  
Vol 58 (7) ◽  
pp. 549-558 ◽  
Author(s):  
M. E. Martens ◽  
C. P. Lee

Several aspects of fatty acid metabolism have been examined in skeletal muscle mitochondria from both strain 129 dystrophic (dy/dy) and myodystrophic (myd/myd) mice. Skeletal muscle mitochondria from dy/dy mice showed significantly decreased state 3 respiratory rates with both palmityl- and acetyl-carnitine + malate as substrates when compared with their normal littermate controls. A similar, though less severe impairment in acylcarnitine oxidation by mitochondria from myd/myd skeletal muscle has also been shown by us in a previous study. In the present study, kinetic measurements revealed decreased activities of the reverse carnitine palmityltransferase (palmitylcarnitine + CoASH as substrates) in intact mitochondria from dy/dy muscle, and of citrate synthase in myd/myd muscle mitochondria. However, neither of these reactions appeared to be rate limiting for acylcarnitine oxidation in mouse skeletal muscle mitochondria. All other enzyme activities or cofactor contents measured were either comparable to those of controls or were higher. The results reported here indicate that neither of the impairments in acylcarnitine oxidation by skeletal muscle mitochondria from dy/dy or myd/myd mice is due to deficiencies in either carnitine palmityltransferase, carnitine acetyltransferase, citrate synthase, coenzyme A, or substrate-reducible flavoprotein.


2018 ◽  
Vol 28 (12) ◽  
pp. 2494-2504 ◽  
Author(s):  
Sune Dandanell ◽  
Anne-Kristine Meinild-Lundby ◽  
Andreas B. Andersen ◽  
Paul F. Lang ◽  
Laura Oberholzer ◽  
...  

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