Bioenergetic consequences of cardiac phosphocreatine depletion induced by creatine analogue feeding

Jay L. Zweier, William E. Jacobus, Borivoj Korecky, Yvonne Brandejs-Barry

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)20296-20304
Number of pages9
JournalJournal of Biological Chemistry
Volume266
Issue number30
StatePublished - 1991

Fingerprint

Phosphocreatine
Creatine
Energy Metabolism
Adenosine Triphosphate
Adenosine Diphosphate
Acids
Phosphates
Rats
Pressure
Ventricular Pressure
Phosphorylation
Creatine Kinase
Thermodynamics
Oxygen Consumption
Nutrition
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance spectroscopy
Heart Rate
Rate constants
Diet

ASJC Scopus subject areas

  • Biochemistry

Cite this

Zweier, J. L., Jacobus, W. E., Korecky, B., & Brandejs-Barry, Y. (1991). Bioenergetic consequences of cardiac phosphocreatine depletion induced by creatine analogue feeding. Journal of Biological Chemistry, 266(30), 20296-20304.

Bioenergetic consequences of cardiac phosphocreatine depletion induced by creatine analogue feeding. / Zweier, Jay L.; Jacobus, William E.; Korecky, Borivoj; Brandejs-Barry, Yvonne.

In: Journal of Biological Chemistry, Vol. 266, No. 30, 1991, p. 20296-20304.

Research output: Contribution to journalArticle

Zweier, JL, Jacobus, WE, Korecky, B & Brandejs-Barry, Y 1991, 'Bioenergetic consequences of cardiac phosphocreatine depletion induced by creatine analogue feeding', Journal of Biological Chemistry, vol. 266, no. 30, pp. 20296-20304.
Zweier, Jay L. ; Jacobus, William E. ; Korecky, Borivoj ; Brandejs-Barry, Yvonne. / Bioenergetic consequences of cardiac phosphocreatine depletion induced by creatine analogue feeding. In: Journal of Biological Chemistry. 1991 ; Vol. 266, No. 30. pp. 20296-20304.
@article{3a4c27c5d2004dd39317e862e99c01e7,
title = "Bioenergetic consequences of cardiac phosphocreatine depletion induced by creatine analogue feeding",
abstract = "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.",
author = "Zweier, {Jay L.} and Jacobus, {William E.} and Borivoj Korecky and Yvonne Brandejs-Barry",
year = "1991",
language = "English (US)",
volume = "266",
pages = "20296--20304",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "30",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=0025757376&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025757376&partnerID=8YFLogxK

M3 - Article

VL - 266

SP - 20296

EP - 20304

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 30

ER -