The activity of îhe pyruvate dehydrogenase (PDH) complex is regulated by phosphorylatioii in a tissue-specific manner by four different pyruvate dehydrogenase kinase (PDK) isoenzymes. Unique tissue distribution and kinetitcharacteristics of these kinases provide tissue-specific regulation of Uie complex. This study investigated whether metabolic conditions known to alter the activity and phosphorylation state of the PDH complex have specific effects upon the expression levels of PDK isoenzymes in rat liver and skeletal muscle (gastrocnemius). Immunoblot analysis revealed marked increases in the amount of PDK4 in skeletal muscle and of both PDK2 and PDK4 in liver of tarvcd rats. Refeeding starved rats reversed these increases in PDK isoen/vme amounts. Starvation likewise increased the abundance of PDK4 mRNA in skeletal muscle and the abundance of both PDK2 and PDK4 mRNA in liver. Refeeding was again effective in reversing these changes. Pronounced increases of PDK4 protein and message level were also found in skeletal muscle but not in the liver of rats fed a high-fat diet. Thus, starvation arid high-fat diet induce tissuespecific overexpression of PDK isoenzymes that leads to greater PDK activity, increased phosphorylation and therefore lower activity of the PDH complex. These findings indicate thaï regulation of expression of PDK isoenzyme is an important control mechanism for long term control of the activity of the PDH complex in rat liver and skeletal muscle. (Supported by giants DK-171-1 and GMM262 from U.S. PHS>.
|Original language||English (US)|
|State||Published - Dec 1 1998|
ASJC Scopus subject areas
- Molecular Biology