Abstract
In exercising muscle, creatine kinase ensures that mismatch between ATP supply and ATP use results in net phosphocreatine (PCr) splitting. This, inter alia, makes 31P magnetic resonance spectroscopy a useful tool for studying muscle ‘energy metabolism’ noninvasively in vivo. We combined this with near–infrared spectroscopy (NIRS) to study ATP synthesis and oxygenation in calf muscle of normal subjects and patients with peripheral vascular disease. Experimental and clinical details and basic data have been published elsewhere (G.J. Kemp et al., Journal of Vascular Surgery 34 (2001), 1103–10); we here propose an analysis of interactions between metabolic ‘error signals’ and cellular PO2 (estimated from NIRS changes, provisionally assumed to reflect deoxymyoglobin). Post–exercise PCr recovery is monoexponential, and the linear relationship between PCr resynthesis rate (= oxidative ATP synthesis) and the perturbation in PCr (conceptually the simplest error signal) is consistent with negative feedback. In patients the inferred ‘mitochondrial capacity’ (= oxidative ATP synthesis at ‘zero’ PCr) is decreased by 53±6%, leading to reduced oxidative ATP contribution in exercise, because of increased deoxygenation. Increased PCr perturbation partially outweighs cellular hypoxia, but as low cellular PO2 is required for capillary–mitochondrion O2 diffusion, rate–signal relationships may overstate maximum oxidative ATP synthesis rate.
Highlights
What 31P magnetic resonance spectroscopy (MRS) measures is limited in scope, sensitivity and quantifiability, but it does offer a valuable noninvasive window on ATP turnover in exercise
In this paper we review some of the principles of quantitative interpretation, and offer an analysis of relationships between tissue metabolism and vascular O2 transport as studied by combining 31P MRS and near-infrared spectroscopy (NIRS) in normal subjects and in patients where these processes are impaired by peripheral vascular disease
The key advantage of 31P MRS is the ability to acquire multiple time-resolved measurements of exercise-recovery changes in phosphocreatine (PCr), inorganic phosphate (Pi), cytosolic pH, free ADP and the free energy of ATP hydrolysis (∆GATP), which can be used to study important aspects of ATP turnover and cellular acid-base physiology (H+ handling) [1,2]. One reason for this is the centrality to energy metabolism of the creatine kinase (CK) equilibrium, which has two main roles: first, to facilitate the diffusion of ‘high energy phosphates’ from sites of ATP production to sites of ATP use
Summary
What 31P magnetic resonance spectroscopy (MRS) measures is limited in scope, sensitivity and quantifiability, but it does offer a valuable noninvasive window on ATP turnover in exercise. The key advantage of 31P MRS is the ability to acquire multiple time-resolved measurements of exercise-recovery changes in phosphocreatine (PCr), inorganic phosphate (Pi), cytosolic pH, free ADP and the free energy of ATP hydrolysis (∆GATP), which can be used to study important aspects of ATP turnover (energy metabolism) and cellular acid-base physiology (H+ handling) [1,2] One reason for this is the centrality to energy metabolism of the creatine kinase (CK) equilibrium, which has two main roles: first, to facilitate the diffusion of ‘high energy phosphates’ from sites of ATP production to sites of ATP use In the second role the CK system is an integrating comparator of rates of ATP synthesis and ATP use [5,6], and either the fall in [PCr] or the concomitant increases in [ADP], [Pi] and ∆GATP are potential closed-loop (negative-feedback) ‘error signals’ to regulate ATP production [2,5,6,7,8,9]
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