Interrelations of ATP synthesis and proton handling in ischaemically exercising human forearm muscle studied by 31P magnetic resonance spectroscopy

J Physiol. 2001 Sep 15;535(Pt 3):901-28. doi: 10.1111/j.1469-7793.2001.00901.x.

Abstract

1. In ischaemic exercise ATP is supplied only by glycogenolysis and net splitting of phosphocreatine (PCr). Furthermore, 'proton balance' involves only glycolytic lactate/H+ generation and net H+ 'consumption' by PCr splitting. This work examines the interplay between these, metabolic regulation and the creatine kinase equilibrium. 2. Nine male subjects (age 25-45 years) performed finger flexion (7 % maximal voluntary contraction at 0.67 Hz) under cuff ischaemia. 31P magnetic resonance spectra were acquired from finger flexor muscle in a 4.7 T magnet using a 5 cm surface coil. 3. Initial PCr depletion rate estimates total ATP turnover rate; glycolytic ATP synthesis was obtained from this and changes in [PCr], and then used to obtain flux through 'distal' glycolysis (phosphofructokinase and beyond) to lactate; 'proximal' flux (through phosphorylase) was obtained from this and changes in [phosphomonoester]. Total H+ load (lactate load less H+ consumption) was used to estimate cytosolic buffer capacity (beta). 4. Glycolytic ATP synthesis increased from near zero while PCr splitting declined. Net H+ load was approximately linear with pH, suggesting beta = 20 mmol x l(-1) (pH unit)(-1) at rest, increasing as pH falls. 5. Relationships between glycolytic rate and changes in [PCr] (i.e. the time-integrated mismatch between ATP use and production), and thus also [P(i)] (substrate for phosphorylase), suggest that increase in glycolysis is due partly to 'open-loop' Ca2+-dependent conversion of phosphorylase b to a, and partly to the 'closed loop' increase in P(i) consequent on net PCr splitting. 6. The 'settings' of these mechanisms have a strong influence on changes in pH and metabolite concentrations.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adenosine Monophosphate / metabolism
  • Adenosine Triphosphate / biosynthesis*
  • Adult
  • Algorithms
  • Cytosol / metabolism
  • Exercise / physiology*
  • Glycogen / biosynthesis
  • Glycogen / metabolism
  • Glycolysis
  • Humans
  • Hydrogen-Ion Concentration
  • Ischemia / physiopathology
  • Kinetics
  • Lactates / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / metabolism*
  • Phosphocreatine / metabolism
  • Phosphofructokinases / metabolism
  • Protons

Substances

  • Lactates
  • Protons
  • Phosphocreatine
  • Adenosine Monophosphate
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Glycogen
  • Phosphofructokinases