Cellular energy utilization and molecular origin of standard metabolic rate in mammals

Abstract

The molecular origin of standard metabolic rate and thermogenesis in mammals is examined. It is pointed out that there are important differences and distinctions between the cellular reactions that 1) couple to oxygen consumption, 2) uncouple metabolism, 3) hydrolyze ATP, 4) control metabolic rate, 5) regulate metabolic rate, 6) produce heat, and 7) dissipate free energy. The quantitative contribution of different cellular reactions to these processes is assessed in mammals. We estimate that approximately 90% of mammalian oxygen consumption in the standard state is mitochondrial, of which approximately 20% is uncoupled by the mitochondrial proton leak and 80% is coupled to ATP synthesis. The consequences of the significant contribution of proton leak to standard metabolic rate for tissue P-to-O ratio, heat production, and free energy dissipation by oxidative phosphorylation and the estimated contribution of ATP-consuming processes to tissue oxygen consumption rate are discussed. Of the 80% of oxygen consumption coupled to ATP synthesis, approximately 25-30% is used by protein synthesis, 19-28% by the Na(+)-K(+)-ATPase, 4-8% by the Ca2(+)-ATPase, 2-8% by the actinomyosin ATPase, 7-10% by gluconeogenesis, and 3% by ureagenesis, with mRNA synthesis and substrate cycling also making significant contributions. The main cellular reactions that uncouple standard energy metabolism are the Na+, K+, H+, and Ca2+ channels and leaks of cell membranes and protein breakdown. Cellular metabolic rate is controlled by a number of processes including metabolic demand and substrate supply. The differences in standard metabolic rate between animals of different body mass and phylogeny appear to be due to proportionate changes in the whole of energy metabolism. Heat is produced by some reactions and taken up by others but is mainly produced by the reactions of mitochondrial respiration, oxidative phosphorylation, and proton leak on the inner mitochondrial membrane. Free energy is dissipated by all cellular reactions, but the major contributions are by the ATP-utilizing reactions and the uncoupling reactions. The functions and evolutionary significance of standard metabolic rate are discussed.

Regulation of gene expression is associated with tolerance of the Arctic copepod Calanus glacialis to CO2‐acidified sea water

“…While we did not measure swimming behavior or escape response speed, larvae of other crustaceans including the American lobster ( Homarus americanus ) show higher swimming speeds at low pH (Waller, Wahle, Mcveigh, & Fields, 2016). Actinomyosin ATPase is a considerable component of the cellular energy budget (Rolfe & Brown, 1997). If an organism is energy‐limited, upregulation of this energy‐demanding process may lead to less energy for fitness‐related processes such as growth and development, although we did not detect declines in developmental time, body weight, or C:N ratio, or an increase in respiration in the C. glacialis nauplii with low pH (Bailey et al., 2016).…”

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

“…This force drives the protons back into the matrix through ATP synthase, which couples proton transport across the membrane to phosphorylation of ADP [18]. The observation that mitochondria still consume oxygen when ADP phosphorylation is inhibited demonstrates that the coupling of respiration to ATP synthesis is imperfect ; in fact, State 4 respiration is mainly due to uncoupling [19,20]. The coupling of oxidative phosphorylation is impaired by the existence of certain leaks through the mitochondrial inner membrane [19][20][21][22][23][24][25][26].…”

The Expensive Brain: A framework for explaining evolutionary changes in brain size

“…Muscle tissue is not as costly per unit weight at rest as brain tissue, but the large size of some muscles makes them sizeable allocation targets (skeletal muscles use 20% of resting metabolism in humans, and 30% in rats, Rolfe and Brown 1997). This suggests that relatively under-muscled organisms, such as primates, may be able to afford larger brains in part through this mechanism.…”