Pyruvate kinase, enzymic activity liver metabolism

DCA is an inhibitor of pyruvate dehydrogenase kinase, the enzyme that regulates pyruvate dehydrogenase (PDH) activity by phosphorylation of the Ex subunit, leading to a decrease in PDH activity (see Chapter 7). DCA has been used to lower lactate levels in some patients with MELAS. Stimulation of PDH activity reduces the release of lactate from peripheral tissues and enhances its metabolism by the liver. Since prolonged use of DCA may lead to sensory neuropathy, treatment must be closely monitored. 

The patient s RBC ADA activity was 43 000 nmol.min . ml RBC " (normal values 495 i 60), There was an about 3-fold increase of red cell pyrimidine 5 -nucleotidase and orotate phosphoribosyl-transferase, whereas other enzymes of purine and pyrimidine metabolism (inosine phosphorylase, adenosine kinase, adenine phosphoribo-syltransferase, hypoxanthine-guanine-phosphoribosyltransferase, phosphoribosylpyrophosphate synthetase) were normal or slightly elevated. There was a 6-fold increase of pyruvate kinase activity relatively to comparably reticulocyte-rich blood, and a 1.5 to 3-fold increase of the other enzymatic activities of glucose and glutathione metabolism. Plasma ADA was much elevated (30.5 pmol.min . ml normal value 5.1 - 2.5), probably reflecting intravascular hemolysis. ADA activity in lymphocytes (2.13 nmol.min 1.10 cells normal 1.93 0.61) and in fibroblasts (26 nmol.min l.mg protein 1 normal range 14-118) was normal, whereas the small increase of activity in platelets (59.5 nmol.min . 10 cells control 26.7) and in the liver (8.4 pmol.min . mg protein" normal ... 

---