大鼠肝脏和AS-30D肝癌线粒体中钙敏感异柠檬酸脱氢酶和2-氧代戊二酸脱氢酶活性

Calcium sensitive isocitrate and 2-oxoglutarate dehydrogenase activities in rat liver and AS-30D hepatoma mitochondria.

作者信息

Murphy A N, Kelleher J K, Fiskum G

机构信息

Department of Biochemistry, George Washington University, School of Medicine and Health Sciences, Washington, D.C. 20037.

出版信息

Biochem Biophys Res Commun. 1988 Dec 30;157(3):1218-25. doi: 10.1016/s0006-291x(88)81004-0.

DOI:10.1016/s0006-291x(88)81004-0

PMID:3207422

Abstract

NAD+-isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase in extracts of mitochondria from the highly malignant AS-30D rat hepatoma cell line demonstrate Ca2+ sensitivities and affinities for substrates similar to those of normal liver mitochondria. However, the maximal activities of NAD+- and NADP+-dependent isocitrate dehydrogenase were found to be 8 and 3.5 fold higher in hepatoma mitochondrial extracts than those of liver mitochondria, whereas maximal activities of succinate and 2-oxoglutarate dehydrogenases were similar in the two tissues. At pyridine nucleotide concentrations giving the lowest physiological NADH/NAD+ ratio, NAD+-isocitrate dehydrogenase activity in hepatoma mitochondrial extracts was completely inhibited at subsaturating concentrations of Ca2+, substrate, and NAD+, in contrast to rat liver mitochondrial extracts which retained significant activity.

摘要

来自高恶性AS - 30D大鼠肝癌细胞系的线粒体提取物中的NAD⁺ - 异柠檬酸脱氢酶和2 - 氧代戊二酸脱氢酶，对Ca²⁺的敏感性以及对底物的亲和力与正常肝脏线粒体相似。然而，发现肝癌线粒体提取物中NAD⁺ - 和NADP⁺ - 依赖的异柠檬酸脱氢酶的最大活性分别比肝脏线粒体高8倍和3.5倍，而琥珀酸脱氢酶和2 - 氧代戊二酸脱氢酶在这两种组织中的最大活性相似。在吡啶核苷酸浓度达到最低生理NADH/NAD⁺比率时，肝癌线粒体提取物中的NAD⁺ - 异柠檬酸脱氢酶活性在Ca²⁺、底物和NAD⁺的亚饱和浓度下被完全抑制，相比之下大鼠肝脏线粒体提取物仍保留显著活性。