The term homeostasis traditionally refers to the maintenance of a relatively constant internal milieu in the face of changing environmental conditions or changing physiological function. Tissues such as skeletal and cardiac muscles must sustain very large-scale changes in ATP turnover rate during equally large changes in work. In many skeletal muscles, these changes can exceed 100-fold. In unique biological circumstances (for example, during periods of oxygen limitation, vasoconstriction and hypometabolism), tissues such as skeletal muscles may be obliged to sustain further decreases in ATP turnover rates and operate for varying periods at seriously suppressed ATP turnover rates. Examination of a number of cellular and whole-organism systems identifies ATP concentration as a key parameter of the interior milieu that is nearly universally "homeostatic'; it is common to observe no change in ATP concentration even while the change in its turnover rate can increase or decrease by two orders of magnitude. A large number of other intermediates of cellular metabolism are also regulated within narrow concentration ranges, but none seemingly as precisely as is [ATP]. In fact, the only other metabolite in aerobic energy metabolism that is seemingly as "homeostatic' is oxygen-at least in working muscles. The central regulatory question is how such homeostasis of key intermediates in pathways of energy supply and energy demand is achieved.

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