Kinetic, Thermodynamic, and Developmental Consequences of Deleting Creatine Kinase Isoenzymes from the Heart

[gamma-P]ATP. Developmental changes in the main fetal isoform of CK (BB-CK) were unaffected by loss of other CK isoenzymes. In hearts lacking both M- and Mt-CK, the rate of ATP synthesis from PCr was only 9% of the rate of ATP synthesis from oxidative phosphorylation demonstrating a lack of any high energy phosphate shuttle. We also found that the intrinsic activities of the BB-CK and the MM-CK isoenzymes were equivalent. Finally, combined loss of M- and Mt-CK (but not loss of only M-CK) prevented the amount of free energy released from ATP hydrolysis from increasing when pyruvate was provided as a substrate for oxidative phosphorylation. -->
ISSN: 0021-9258
DOI: 10.1074/jbc.m001932200
Přístupová URL adresa: https://explore.openaire.eu/search/publication?articleId=doi_________::f4f39010dae94b077d5b437ccadb0ee0
https://doi.org/10.1074/jbc.m001932200
Rights: OPEN
Přírůstkové číslo: edsair.doi...........f4f39010dae94b077d5b437ccadb0ee0
Autor: Kurt W. Saupe, James C.A. Hopkins, Joanne S. Ingwall, Matthias Spindler, Weiqun Shen
Rok vydání: 2000
Předmět:
Zdroj: Journal of Biological Chemistry. 275:19742-19746
ISSN: 0021-9258
DOI: 10.1074/jbc.m001932200
Popis: Creatine kinase (CK) exists as a family of isoenzymes in excitable tissue. We studied isolated perfused hearts from mice lacking genes for either the main muscle isoform of CK (M-CK) or both M-CK and the main mitochondrial isoform (Mt-CK) to determine 1) the biological significance of CK isoenzyme shifts, 2) the necessity of maintaining a high CK reaction rate, and 3) the role of CK isoenzymes in establishing the thermodynamics of ATP hydrolysis. (31)P NMR was used to measure [ATP], [PCr], [P(i)], [ADP], pH, as well as the unidirectional reaction rate of PCr--> [gamma-P]ATP. Developmental changes in the main fetal isoform of CK (BB-CK) were unaffected by loss of other CK isoenzymes. In hearts lacking both M- and Mt-CK, the rate of ATP synthesis from PCr was only 9% of the rate of ATP synthesis from oxidative phosphorylation demonstrating a lack of any high energy phosphate shuttle. We also found that the intrinsic activities of the BB-CK and the MM-CK isoenzymes were equivalent. Finally, combined loss of M- and Mt-CK (but not loss of only M-CK) prevented the amount of free energy released from ATP hydrolysis from increasing when pyruvate was provided as a substrate for oxidative phosphorylation.
Databáze: OpenAIRE
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