Pitfalls in the use of 2-octynoic acid as an in vivo model of medium-chainacyl-coenzyme A dehydrogenase deficiency: Ketone turnover and metabolite studies in the rat
Jm. Fletcher et Jj. Pitt, Pitfalls in the use of 2-octynoic acid as an in vivo model of medium-chainacyl-coenzyme A dehydrogenase deficiency: Ketone turnover and metabolite studies in the rat, METABOLISM, 48(6), 1999, pp. 685-688
2-Octynoic acid was administered by intraperitoneal injection to fasted Spr
ague-Dawley rats in an attempt to simulate medium-chain acyl-coenzyme A deh
ydrogenase (MCAD) deficiency. The resultant urine organic acid profile show
ed a mild dicarboxylic aciduria but lacked the glycine conjugates character
istic of MCAD deficiency. Further studies with infused C-13(4)-3-hydroxybut
yrate and C-13(2)-acetoacetate demonstrated reduced ketone production in tr
eated rats compared with control animals. Although plasma ketone body conce
ntrations were low in treated rats, plasma free fatty acids were also low,
thereby providing diminished substrate for ketone production. This is the r
everse of the finding in children with MCAD deficiency, who have low levels
of plasma ketones despite elevated free fatty acids. These animal studies
were therefore not helpful in improving our understanding of ketone body ki
netics in children with MCAD deficiency. Copyright (C) 1999 by W.B. Saunder
s Company.