What Do Magnetic Resonance–Based Measurements of Pi→ATP Flux Tell Us About Skeletal Muscle Metabolism?

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FIG. 1.
FIG. 1.

Pi→ATP flux and exchange rate constant in resting human muscle: a quantitative summary of the literature. This figure summarizes the results of a number of published studies of human muscle using various experimental methods. Each point (or pair of linked points) shows the mean in a single reported study. A shows estimates of oxidative ATP synthesis by five experimental methods: Method 1, from the Pi→ATP flux measured by 31P MRS MT (13,1316,20,2325,2832,45,73); Method 2, from 13C MRS measurements of TCAC rate (1216); Method 3, from AVD measurements of O2 consumption (4751,7479) [and three articles cited in Table 3 of van Beekvelt et al. (11)]; Method 4, from near-infrared spectrophotometry measurements of O2 consumption in ischemic muscle (4,80,81) [and eight articles cited in Table 3 of van Beekvelt et al. (11)]; and Method 5, from 31P MRS measurements of PCr decrease (sometimes with correction for glycolytic ATP synthesis) in ischemic muscle (2,410) [and three articles cited in Table 3 of van Beekvelt et al. (11)]. The dashed line shows the overall mean value for each method. The inset shows the same data in logarithmic form to focus on the values obtained by Methods 3–5 (which are similar to values given by 15O positron emission tomography [39], omitted here for brevity). B shows mean Pi→ATP flux measured by 31P MRS MT as a function of cytosolic [Pi] in published studies of normal muscle unstimulated by insulin (closed circles) (1,2,13,28,29,32,73) and also during hyperinsulinemic-euglycemic clamp stimulation in a single study (open circle linked by a line to the corresponding unstimulated point) (28). The figure also shows data from insulin-resistant offspring of patients with type 2 diabetes (open triangle, linked to the closed triangle representing data from the unstimulated muscle) in a single study (20) (as absolute values of [Pi] are not reported, we assume a basal value equal to the mean of the other studies in this figure). C shows the pseudo–first-order rate constant for flux between Pi and ATP in the studies shown in B; lines link the data from insulin stimulation and IR to the matching control points. In this review, concentrations are expressed as mmol/L cytosolic water (which we call mM), recalculated where necessary from published sources assuming leg muscle mass = 10 kg, muscle density = 1.049 kg/L, and muscle cell water = 0.67 L/kg wet weight (17); Vo2/TCAC rate = 3; and 1 mol O2 = 25.5 l (82); for Methods 2, 3, and 4, P:O is taken as 2.16 on the basis of mouse experiments combining near-infrared spectrophotometry and 31P MRS during ischemia (83) (see also legend to Fig. 2).

This Article

  1. Diabetes vol. 61 no. 8 1927-1934