TY - JOUR
T1 - Bioenergetic consequences of cardiac phosphocreatine depletion induced by creatine analogue feeding
AU - Zweier, Jay L.
AU - Jacobus, William E.
AU - Korecky, Borivoj
AU - Brandejs-Barry, Yvonne
PY - 1991
Y1 - 1991
N2 - To further evaluate the bioenergetic role of phosphocreatine, we assessed several parameters in normal and depleted rat hearts. Rats were fed (8 weeks) a diet containing either 1% β-guanidinoproprionic acid or 2% β-guanidinobutyric acid (β-GBA), resulting in an 80% phosphocreatine depletion compared to controls. Left ventricular pressure-volume curves were obtained to determine contractile function. At any volume, the developed pressure in depleted hearts was lower than in controls. At the plateau, the rate-pressure product was between 37-45% lower: 34,000 (β-GBA), 30,174 (β-guanidinoproprionic acid) versus 54,400 (control). 31P NMR spectroscopy on β-GBA-treated hearts obtained the [ATP] and [phosphocreatine], which with saturation transfer estimated the rates of creatine kinase and ATP production. In depleted hearts, the rate constant for ATP synthesis from phosphocreatine was increased 33%. However, the flux was 72% lower. ATP production from ADP and Pi were similar under normal conditions, in spite of higher rates of oxygen consumption in the depleted hearts. The addition of 50 mM creatine to control perfusate had no effect on function or high energy phosphates. In contrast, a 28% increase in function and a 52% increase in [phosphocreatine] was seen in β-GBA hearts. There was a marked increase in free [ADP] in β-GBA hearts, resulting in a lower estimated ATP phosphorylation potential. Overall, the results suggest that phosphocreatine may play an important function by optimizing the thermodynamics of cardiac high energy phosphate utilization.
AB - To further evaluate the bioenergetic role of phosphocreatine, we assessed several parameters in normal and depleted rat hearts. Rats were fed (8 weeks) a diet containing either 1% β-guanidinoproprionic acid or 2% β-guanidinobutyric acid (β-GBA), resulting in an 80% phosphocreatine depletion compared to controls. Left ventricular pressure-volume curves were obtained to determine contractile function. At any volume, the developed pressure in depleted hearts was lower than in controls. At the plateau, the rate-pressure product was between 37-45% lower: 34,000 (β-GBA), 30,174 (β-guanidinoproprionic acid) versus 54,400 (control). 31P NMR spectroscopy on β-GBA-treated hearts obtained the [ATP] and [phosphocreatine], which with saturation transfer estimated the rates of creatine kinase and ATP production. In depleted hearts, the rate constant for ATP synthesis from phosphocreatine was increased 33%. However, the flux was 72% lower. ATP production from ADP and Pi were similar under normal conditions, in spite of higher rates of oxygen consumption in the depleted hearts. The addition of 50 mM creatine to control perfusate had no effect on function or high energy phosphates. In contrast, a 28% increase in function and a 52% increase in [phosphocreatine] was seen in β-GBA hearts. There was a marked increase in free [ADP] in β-GBA hearts, resulting in a lower estimated ATP phosphorylation potential. Overall, the results suggest that phosphocreatine may play an important function by optimizing the thermodynamics of cardiac high energy phosphate utilization.
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M3 - Article
C2 - 1939088
AN - SCOPUS:0025757376
SN - 0021-9258
VL - 266
SP - 20296
EP - 20304
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 30
ER -