Calcium sensitive isocitrate and 2-oxoglutarate dehydrogenase activities in rat liver and AS-30D hepatoma mitochondria.
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.
Murphy
A N
AN
Department of Biochemistry, George Washington University, School of Medicine and Health Sciences, Washington, D.C. 20037.
Kelleher
J K
JK
Fiskum
G
G
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D005260:Female; D007521:Isocitrate Dehydrogenase / Q000378:metabolism*; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism*; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology*; D009243:NAD / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D009243:NAD; D009249:NADP; D007521:Isocitrate Dehydrogenase; D007658:Ketone Oxidoreductases; D007655:Ketoglutarate Dehydrogenase Complex; D013385:Succinate Dehydrogenase; D002118:Calcium