TY - JOUR
T1 - High-energy phosphate transfer in human muscle
T2 - Diffusion of phosphocreatine
AU - Gabr, Refaat E.
AU - El-Sharkawy, Abdel Monem M.
AU - Schär, Michael
AU - Weiss, Robert G.
AU - Bottomley, Paul A.
PY - 2011/7
Y1 - 2011/7
N2 - The creatine kinase (CK) reaction is central to muscle energetics, buffering ATP levels during periods of intense activity via consumption of phosphocreatine (PCr). PCr is believed to serve as a spatial shuttle of high-energy phosphate between sites of energy production in the mitochondria and sites of energy utilization in the myofibrils via diffusion. Knowledge of the diffusion coefficient of PCr (DPCr) is thus critical for modeling and understanding energy transport in the myocyte, but DPCr has not been measured in humans. Using localized phosphorus magnetic resonance spectroscopy, we measured DPCr in the calf muscle of 11 adults as a function of direction and diffusion time. The results show that the diffusion of PCr is anisotropic, with significantly higher diffusion along the muscle fibers, and that the diffusion of PCr is restricted to a ̃28-μm pathlength assuming a cylindrical model, with an unbounded diffusion coefficient of ̃0.69 × 10-3 mm2/s. This distance is comparable in size to the myofiber radius. On the basis of prior measures of CK reaction kinetics in human muscle, the expected diffusion distance of PCr during its half-life in the CK reaction is ̃66 μm. This distance is much greater than the average distances between mitochondria and myofibrils. Thus these first measurements of PCr diffusion in human muscle in vivo support the view that PCr diffusion is not a factor limiting high-energy phosphate transport between the mitochondria and the myofibrils in healthy resting myocytes.
AB - The creatine kinase (CK) reaction is central to muscle energetics, buffering ATP levels during periods of intense activity via consumption of phosphocreatine (PCr). PCr is believed to serve as a spatial shuttle of high-energy phosphate between sites of energy production in the mitochondria and sites of energy utilization in the myofibrils via diffusion. Knowledge of the diffusion coefficient of PCr (DPCr) is thus critical for modeling and understanding energy transport in the myocyte, but DPCr has not been measured in humans. Using localized phosphorus magnetic resonance spectroscopy, we measured DPCr in the calf muscle of 11 adults as a function of direction and diffusion time. The results show that the diffusion of PCr is anisotropic, with significantly higher diffusion along the muscle fibers, and that the diffusion of PCr is restricted to a ̃28-μm pathlength assuming a cylindrical model, with an unbounded diffusion coefficient of ̃0.69 × 10-3 mm2/s. This distance is comparable in size to the myofiber radius. On the basis of prior measures of CK reaction kinetics in human muscle, the expected diffusion distance of PCr during its half-life in the CK reaction is ̃66 μm. This distance is much greater than the average distances between mitochondria and myofibrils. Thus these first measurements of PCr diffusion in human muscle in vivo support the view that PCr diffusion is not a factor limiting high-energy phosphate transport between the mitochondria and the myofibrils in healthy resting myocytes.
KW - Creatine kinase shuttle
KW - Energy metabolism
KW - Human studies
KW - Myocyte
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U2 - 10.1152/ajpcell.00500.2010
DO - 10.1152/ajpcell.00500.2010
M3 - Article
C2 - 21368292
AN - SCOPUS:79959854515
SN - 0363-6143
VL - 301
SP - C234-C241
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 1
ER -