Spontaneous animal models of
inborn errors of metabolism are valuable tools for defining the pathogenesis of these disorders and also the mechanism of various therapeutic approaches. In the present study, we have employed BALB/cByJ mice with an autosomal recessive deficiency of
short-chain acyl-CoA dehydrogenase (SCAD). These animals were characterized by a marked urinary excretion of ethylmalonic and methylsuccinic
acids along with butyrylglycine. Using adult homozygous mice we have studied the basic cerebral and hepatic profile of
carnitine,
ammonia, and energy metabolism. The effects of fasting and a short-term supplement of
L-carnitine have been evaluated in comparison with control BALB/cJ mice. The mutant mice had low levels of
acetyl-CoA and high levels of
lactate compared to control mice. Fasting aggravated this condition by further decreasing
acetyl-CoA and increasing
lactate levels in the mutant mice. Free
carnitine levels were significantly decreased in liver with fasting. Long-chain acylcarnitines were significantly lower in the brain of mutant mice. A short-term supplementation of
L-carnitine resulted in general increases of
carnitine levels in liver and muscle, but they still remained lower in mutant BALB/cByJ mice as compared to control BALB/cJ mice.
L-Carnitine treatment increased cerebral
CoA-SH levels and both hepatic and cerebral
acetyl-CoA levels in mutant mice.
Hyperammonemia which has been described frequently in
acyl-CoA dehydrogenase deficiencies was not observed in adult BALB/cByJ mice. This could be due to a rapid conjugation of
butyryl-CoA with
glycine by an increased activity of
glycine N-acyltransferase.