CARDIAC CONSEQUENCES OF SECONDARY CARNITINE DEFICIENCY

描述(改编自申请人的摘要)：鉴于 继发性肉碱缺乏症发生率较高，申请人 建议研究这种情况对心脏的影响。这个 申请人的目的是调查以下情况的长期后果 继发性肉碱缺乏对心肌收缩功能的影响 底物氧化、长链乙酰辅酶A和肉碱的积累 酯，以及正常心脏所需的一些关键酶的mRNA 功能。肌球蛋白ATPase亚型的活性和mRNA水平， 肌浆网Ca++-ATPase和线粒体细胞色素氧化酶 将会被测量。此外，己糖激酶、丙酮酸的活性 脱氢酶，3-羟基酰辅酶A脱氢酶，肉碱棕榈酰 测定转移酶和柠檬酸合成酶。它是 假设心肌基质的慢性改变 肉碱缺乏引起的代谢导致基因改变 这些酶的表达，进而导致心肌病。

DESCRIPTION (adapted from the applicant's abstract): 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.