Age-related compensatory activation of pyruvate dehydrogenase complex in rat heart.
Mitochondrial uptake and beta-oxidation of long-chain fatty acids are markedly impaired in the aging rat heart. While these alterations would be expected to adversely affect overall pyridine nucleotides, NADH levels do not change significantly with age. This conundrum suggests that specific compensatory mechanisms occur in the aging heart. The comparison of cardiac pyruvate dehydrogenase complex (PDC) kinetics in 4- and 24- to 28-month-old F344 rats revealed a 60% significant increase in V(max) with no change in PDC expression, and a 1.6-fold decrease in the Michaelis constant (K(m)) in old compared to young rats. The observed kinetic adjustments were selective to PDC, as neither the V(max) nor K(m) of citrate synthase changed with age. PDC kinase-4 mRNA levels decreased by 57% in old vs young rat hearts and correlated with a 45% decrease in PDC phosphorylation. We conclude that PDC from old rat hearts catabolizes pyruvate more efficiently due to an adaptive change in phosphorylation.
Moreau
Régis
R
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-6512, USA.
Heath
Shi-Hua D
SH
Doneanu
Catalin E
CE
Harris
Robert A
RA
Hagen
Tory M
TM
D000375:Aging / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003065:Coenzyme A / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation; D004952:Esters / Q000737:chemistry / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013552:Swine
D004952:Esters; D007527:Isoenzymes; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex; D009243:NAD; D002950:Citrate (si)-Synthase; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase; D003065:Coenzyme A