In view of the greater incidence of secondary carnitine deficiencies, the applicant proposes to study the effects of this condition on the heart. The applicant purposes to investigate the long-term consequences of secondary carnitine deficiency on myocardial contractile function, substrate oxidation, accumulation of long chain acyl CoA and carnitine esters, and mRNA for a number of key enzymes required for normal cardiac function. The activities and mRNA levels for myosin ATPase isoforms, sarcoplasmic reticulum Ca++-ATPase, and mitochondrial cytochrome oxidase would be measured. In addition, the activities of hexokinase, pyruvate dehydrogenase, 3-hydroxyacyl CoA dehydrogenase, carnitine palmitoyl transferase and citrate synthetase would be measured. It is hypothesized that the chronic alterations in myocardial substrate metabolism induced by carnitine deficiency results in altered gene expression for these enzymes, which in turn leads to cardiomyopathy.
|Paulson, D J (1998) Carnitine deficiency-induced cardiomyopathy. Mol Cell Biochem 180:33-41|