Pitfalls in the use of 2-octynoic acid as an in vivo model of medium-chain acyl-coenzyme A dehydrogenase deficiency: ketone turnover and metabolite studies in the rat.

2-Octynoic acid was administered by intraperitoneal injection to fasted Sprague-Dawley rats in an attempt to simulate medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. The resultant urine organic acid profile showed a mild dicarboxylic aciduria but lacked the glycine conjugates characteristic of MCAD deficiency. Further studies with infused 13C(4)-3-hydroxybutyrate and 13C(2)-acetoacetate demonstrated reduced ketone production in treated rats compared with control animals. Although plasma ketone body concentrations were low in treated rats, plasma free fatty acids were also low, thereby providing diminished substrate for ketone production. This is the reverse 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 kinetics in children with MCAD deficiency.