Bioenergetic scaling: metabolic design and body-size constraints in mammals.

The cytosolic phosphorylation ratio ([ATP]/[ADP][P(i)]) in the mammalian heart was found to be inversely related to body mass with an exponent of -0.30 (r = 0.999). This exponent is similar to -0.25 calculated for the mass-specific O2 consumption. The inverse of cytosolic free [ADP], the Gibbs energy of ATP hydrolysis (delta G'ATP), and the efficiency of ATP production (energy captured in forming 3 mol of ATP per cycle along the mitochondrial respiratory chain from NADH to 1/2 O2) were all found to scale with body mass with a negative exponent. On the basis of scaling of the phosphorylation ratio and free cytosolic [ADP], we propose that the myocardium and other tissues of small mammals represent a metabolic system with a higher driving potential (a higher delta G'ATP from the higher [ATP]/[ADP][P(i)]) and a higher kinetic gain [(delta V/Vmax)/delta [ADP]] where small changes in free [ADP] produce large changes in steady-state rates of O2 consumption. From the inverse relationship between mitochondrial efficiency and body size we calculate that tissues of small mammals are more efficient than those of large mammals in converting energy from the oxidation of foodstuffs to the bond energy of ATP. A higher efficiency also indicates that mitochondrial electron transport is not the major site for higher heat production in small mammals. We further propose that the lower limit of about 2 g for adult endotherm body size (bumblebee-bat, Estrucan shrew, and hummingbird) may be set by the thermodynamics of the electron transport chain. The upper limit for body size (100,000-kg adult blue whale) may relate to a minimum delta G'ATP of approximately 55 kJ/mol for a cytoplasmic phosphorylation ratio of 12,000 M-1.

研究发现，哺乳动物心脏的胞质磷酸化比率（[ATP]/[ADP][Pᵢ]）与体重呈负相关，相关指数为-0.30（相关系数r=0.999）。该指数与针对质量特异性耗氧量（mass-specific O₂ consumption）计算得到的-0.25相近。胞质游离[ADP]的倒数、ATP水解的吉布斯自由能（ΔG'_ATP），以及ATP生成效率（即沿线粒体呼吸链（mitochondrial respiratory chain）从烟酰胺腺嘌呤二核苷酸（NADH）到1/2 O₂的每一轮循环中，合成3 mol ATP所捕获的能量），均被发现随体重呈负指数异速缩放。基于磷酸化比率与胞质游离[ADP]的异速缩放规律，我们提出：小型哺乳动物的心肌（myocardium）及其他组织构成了一套具有更高驱动势能（因[ATP]/[ADP][Pᵢ]更高而拥有更高的ΔG'_ATP）和更高动力学增益[(ΔV/Vₘₐₓ)/Δ[ADP]]的代谢系统——在该系统中，游离[ADP]的微小变化即可引发稳态耗氧速率的显著改变。基于线粒体效率（mitochondrial efficiency）与体型的负相关关系，我们推算得出：小型哺乳动物的组织在将食物氧化能量转化为ATP键能的过程中，效率高于大型哺乳动物的对应组织。更高的效率同时表明，线粒体电子传递并非小型哺乳动物产热升高的主要位点。我们进一步提出：成年恒温动物（endotherm）的体型下限（约2克，如大黄蜂蝙蝠、埃特鲁里亚鼩鼱和蜂鸟）可能由电子传递链（electron transport chain）的热力学特性所决定。而成年蓝鲸（blue whale，体重100,000千克）的体型上限，则可能与胞质磷酸化比率为12,000 M⁻¹时，ΔG'_ATP的最小值约为55 kJ/mol相关。