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Introduction Although in recent times the application of nmr spectroscopy to living tissues has tended to confirm the role of free ADP in regulating oxidative metabolism (Chance et al., Proc. Natl. Acad. Sci. U.S.A., 83, 9458-9462, 1986), this is only so provided the ADP concentration is below a relatively low threshold value ( 50 pM). What is not clear are the mechanisms that restrain the ADP at this threshold, and nmr studies of the perfused rat heart (From et al., FEBS Lett., 206, 257-261, 1986) and intact dogs (Balaban et al., Science, 232, 1 121-1 123, 1986) have emphasized that respiratory control of heart mitochondria is not a function of free ADP concentration when this threshold is reached. Even more striking and difficult to explain is what limits the fall of ATP concentrations for up to tens of minutes when energy production is severely limited in hearts by ischaemia, while a "buffer" substrate like creatine phosphate disappears in tens of seconds; or again how the ATP pool is apparently replenished periodically during long-term ischaemia as nmr studies of frog muscle seem to show (Keidel et al., Res. Exp. Med., 84, 73-84, 1984). Similar experiments with perfused rat livers found nmr resonances for ATP declining faster than extracted ATP (Murphy et al., Biochemistry, 27, 526-528, 1988). The proposal that this missing nucleotide represented an nmr -invisible pool confined to the mitochondria1 matrix is challenged by the findings that all the ATP is nmr visible in isolated mitochondria (Hutson et al., Biochemistry, 28,4325-4332, 1989) and in the perfused heart (Humphrey and Garlick, Circulation, 80, 498, 1989). By contrast, on the related problem of cell inorganic phosphate concentrations, there is agreement that somewhat less than 50% of the extractable pool is ever nmr visible (see Humphrey et al., Eur. J. Biochem., 191, 755-759, 1990). The inference is that additional new information is required. |
