title: Interrelations of ATP synthesis and proton handling in ischaemically exercising human forearm muscle studied by 31P magnetic resonance spectroscopy.
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.
authors.affiliation: Department of Musculoskeletal Science, University of Liverpool, Liverpool L69 3GA, UK. gkemp@liv.ac.uk
authors.forename: G J
authors.initials: GJ
authors.lastname: Kemp
authors.forename: M
authors.initials: M
authors.lastname: Roussel
authors.forename: D
authors.initials: D
authors.lastname: Bendahan
authors.forename: Y
authors.initials: Y
authors.lastname: Le Fur
authors.forename: P J
authors.initials: PJ
authors.lastname: Cozzone
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000328:Adult; D000465:Algorithms; D003600:Cytosol / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D006003:Glycogen / Q000096:biosynthesis / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007511:Ischemia / Q000503:physiopathology; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D025221:Phosphofructokinases / Q000378:metabolism; D011522:Protons
chemical_list: D007773:Lactates; D011522:Protons; D010725:Phosphocreatine; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006003:Glycogen; D025221:Phosphofructokinases