PYRUVATE INHIBITION OF PYRUVATE-DEHYDROGENASE KINASE - EFFECTS OR PROGRESSIVE STARVATION AND HYPERTHYROIDISM IN-VIVO, AND OF DIBUTYRYL-CYCLIC-AMP AND FATTY-ACIDS IN CULTURED CARDIAC MYOCYTES

Both prolonged starvation and hyperthyroidism evoke stable increases i n cardiac pyruvate dehydrogenase kinase (PDHK) activity, Pyruvate inhi bits PDHK in rat heart mitochondria with activation of PDHC. The sensi tivity of PDHK to inhibition by pyruvate declines after prolonged star vation. In the present study, pyruvate concentrations giving 50% activ e complex (PDHa) in mitochondria fi om fed, central and fed, hyperthyr oid rats were 0.3 and 0.8 mM, respectively, compared with 1.0 and 2.8 mM, respectively in mitochondria from 24-h-starved and 48-h-starved ra ts. The results demonstrate that altered pyruvate sensitivity is not o f necessity linked with altered PDHK activity. PDHK activities in mito chondria prepared from cardiac myocytes from fed rats were increased a fter culture for 24 h with dibutyryl cyclic AMP (50 mu M) plus n-octan oate (1 mM), with a concomitant decline in sensitivity of PDHK to pyru vate inhibition, suggesting that changes in sensitivity of PDHK to pyr uvate inhibition in vivo may be secondary to increased fatty acid supp ly and cyclic AMP concentrations.