Starvation reduces pyruvate dehydrogenase phosphate phosphatase activity in rat kidney.
Pyruvate dehydrogenase complex (PDC) from rat kidney or pig heart previously inactivated by phosphorylation (PDHP) was activated in vitro by PDHP phosphatase from kidneys of starved or fed rats. Starvation for 48 h of the rats from which the PDC was prepared led to a decrease in the rate of activation of PDC at early time periods (< 2 min), particularly at submaximal concentrations of Mg2+. Using intact permeable kidney mitochondria incubated for 15 sec, it was found that starvation of rats more than doubled the Mg2+ concentration at which the half maximal increment of PDC activity (PDCa) was observed. Reduction of PDHP phosphatase activity due to starvation was also apparent when phosphatase was separated from PDC and recombined with PDC from the same or different animals. Intraperitoneal injection of insulin and glucose 1 h before sacrifice of starved rats prevented the reduction of PDHP phosphatase activity whether or not protein synthesis was inhibited. The effect of insulin in restoration of PDHP phosphatase activity of starved rats was not mimicked by 5-methylpyrazole 3-carboxylic acid, an inhibitor of lipolysis. When renal PDHP phosphatase was incubated with pig heart PDC in the presence of 10 mM Mg2+ and 0.1 mM Ca2+ the increment in PDCa, in 1 min was 30% of fully activated PDC activity (PDCt) observed after 15 min. Removal of divalent cations did not affect the increment in 1 min but prevented further increments. Conversely okadaic acid diminished 1 min increment but did not disturb PDCt. It is suggested that the different behaviour of renal PDC from fed and starved animals may partly be due to different divalent cation independent PDHP phosphatase activity.
Cockburn
B N
BN
Department of Biochemistry, Faculty of Medical Sciences, University of the West Indies, St. Augustine, Trinidad, West Indies.
Coore
H G
HG
D000818:Animals; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D019319:Okadaic Acid; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013217:Starvation / Q000378:metabolism*; D013552:Swine
D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D011768:Pyruvate Dehydrogenase Complex; D019319:Okadaic Acid; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase; D008274:Magnesium