Bioenergetic scaling: Metabolic design and body-size constraints in mammals

Abstract

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 (ΔG'(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 ΔG'(ATP) from the higher [ATP]/[ADP][P(i)]) and a higher kinetic gain {(ΔV/V(max))/Δ[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 ΔG'(ATP) of ≃55 kJ/mol for a cytoplasmic phosphorylation ratio of 12,000 M-1.