The percentage of total pyruvate dehydrogenase in the active nonphosphorylated form was measured in intact rat liver mitochondria after rapid separation of the mitochondria through silicone oil and extraction with glycerol buffer at 10”. The contents of ATP, ADP, Mg2+, and Ca2+ in the mitochondrial matrix of separated mitochondria were determined in parallel experiments. Mitochondria were incub...

Hibernating mammals have the ability to decrease their metabolic rate and survive up to 6 months without food in an inactive state where body temperatures approach 0 degrees C. In hibernating 13-lined ground squirrels (Spermophilus tridecemlineatus), oxygen consumption holds at 1/30 to 1/50 of the aroused condition and heart rates are as low as 3-10 beats/min, compared with 200-300 beats/min wh...

Spatial organization of metabolic enzymes allows substrate channeling, which accelerates processing of intermediates. Here, we investigated the effect of substrate channeling on the flux partitioning at a metabolic branch point, focusing on pyruvate metabolism in Saccharomyces cerevisiae. As a platform strain for the channeling of pyruvate flux, PYK1-Coh-Myc strain was constructed in which PYK1...

In a previous work published 4 years ago, an arrest of tumor cell proliferation was obtained with dichloroacetate, an inhibitor of pyruvate dehydrogenase kinase, aiming to dephosphorylate and activate pyruvate dehydrogenase (PDH) [1]. This observation indicates that it may be useful to act as well, on other tumor cell enzymes that change in parallel to PDH, since this leads to a “rewiring of me...

Pyruvate dehydrogenase kinase 4 (PDK4) mRNA was identified as a transcript that was rapidly and generally induced by fibrates in various tissues of the mouse. The time course of induction was much faster than those of typical peroxisome proliferator-activated receptor alpha (PPAR alpha)-regulated peroxisomal mRNAs. Rapid and efficient induction of PDK4 mRNA in various tissues would inactivate p...

1. The activity of pig heart pyruvate dehydrogenase kinase was assayed by the incorporation of [(32)P]phosphate from [gamma-(32)P]ATP into the dehydrogenase complex. There was a very close correlation between this incorporation and the loss of pyruvate dehydrogenase activity with all preparations studied. 2. Nucleoside triphosphates other than ATP (at 100mum) and cyclic 3':5'-nucleotides (at 10...

Following a low carbohydrate diet, there is a shift towards more fat and less carbohydrate oxidation to provide energy to skeletal muscle, both at rest and during exercise. This review summarizes recent work on human skeletal muscle carbohydrate and fat metabolic adaptations to a low carbohydrate diet, focusing mainly on pyruvate dehydrogenase and pyruvate dehydrogenase kinase, and how these ch...

The kinetics of pyruvate phosphorylation by rabbit skeletal muscle pyruvate kinase (EC 2.7.1.40) has been studied with a coupled assay using P-enolpyruvate carboxylase (EC 4.1.1.31) and malate dehydrogenase (EC 1.1.1.37). The reaction sequence is (See journal for formula). Although the equilibrium of the pyruvate kinase reaction by itself strongly favors pyruvate production, the over-all equili...