³¹P magnetization transfer measurements of Pi->ATP flux in exercising human muscle
Williams, Guy Barnett
Carpenter, Thomas Adrian
Kemp, Graham J
ST measurements of Pi->ATP flux in exercising human muscle
Journal of Applied Physiology
American Physiological Society
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Sleigh, A., Savage, D. B., Williams, G. B., Porter, D., Carpenter, T. A., Brindle, K. M., & Kemp, G. J. (2016). ³¹P magnetization transfer measurements of Pi->ATP flux in exercising human muscle. Journal of Applied Physiology
Fundamental criticisms have been made over the use of 31P-MRS magnetization transfer estimates of Pi->ATP flux (VPi-ATP) in human resting skeletal muscle for assessing mitochondrial function. Although the discrepancy in the magnitude of VPi-ATP is now well acknowledged, little is known about its metabolic determinants. Here we use a novel protocol to measure VPi-ATP in human exercising muscle for the first time. Steady state VPi-ATP was measured at rest and over a range of exercise intensities, and compared with suprabasal oxidative ATP synthesis rates estimated from the initial rates of post-exercise phosphocreatine resynthesis (VATP). We define a ‘surplus’ Pi->ATP flux as the difference between VPi-ATP and VATP. The coupled reactions catalyzed by the glycolytic enzymes, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and phosphoglycerate kinase (PGK) have been shown previously to catalyze a measurable exchange between ATP and Pi in some systems and have been suggested to be responsible for this surplus VPi-ATP flux. Surplus VPi-ATP did not change between rest and exercise, even though the concentrations of [Pi] and [ADP], which are substrates for GAPDH and PGK, respectively, increased as expected. However, involvement of these enzymes is suggested by correlations observed between absolute and surplus Pi->ATP flux, both at rest and during exercise, and the intensity of the phosphomonoester peak in the 31P NMR spectrum. This peak includes contributions from sugar phosphates in the glycolytic pathway and changes in its intensity may indicate changes in downstream glycolytic intermediates, including 3-phosphoglycerate, which has been shown to influence the exchange between ATP and Pi.
³¹P magnetization transfer, saturation transfer, Pi<->ATP exchange, exercising muscle
This work was funded by the Clinical Research Infrastructure Grant and the Siemens MAGNETOM 3T Verio scanner is funded by the NIHR via an award to the Cambridge NIHR/Wellcome Trust Clinical Research Facility. DBS is supported by the Wellcome Trust (091551).
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This record's URL: https://www.repository.cam.ac.uk/handle/1810/253111