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

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.