The laws of cell energetics.

Recent progress in membrane bioenergetics studies has resulted in the important discovery that Na+ can effectively substitute for H+ as the energy coupling ion. This means that living cells can possess three convertible energy currencies, i.e. ATP, protonic and sodium potentials. Analysis of interrelations of these components in various types of living cells allows bioenergetic laws of universal applicability to be inferred.     

The energetics of embryonic growth and development. I. Oxygen consumption, biomass growth, and heat production.

A quantitative phenomenological model to describe the relationships between biomass growth rate, oxygen consumption, and heat production in developing embryos has been developed and tested using a wide range of experimental data. The model employs generalized material and energy balances, principles of enzyme kinetics, and an overall metabolic model scheme based on known biochemical principles. The phosphorylation concentration ratio of ATP and ADP occurs naturally and becomes a significant parameter in the analysis. The model is applied to the growth of Escherichia coli, Oryzias latipes, chick spinal cord, and whole chicken eggs. Excellent agreement between the model and the experimental data is obtained. In a succeeding paper (Part II) environmental effects and growth efficiency are discussed.     

Role of physiological energetics in ecotoxicology.

1. The role of physiological energetic measurements combined with chemical analyses of contaminants in body tissues of mussels in fundamental toxicological studies and pollution monitoring programmes is outlined. 2. Important features of this toxicological approach are briefly reviewed, including aspects of bioaccumulation, sensitivity, quantitative concentration-response relationships, QSARs, mechanistic interpretation, ecological relevance, integration of the consequences of multiple mechanisms of toxicity and effects of contaminant mixtures and application to laboratory and field studies. 3. This review focuses particularly on recent advances in understanding and predicting the effects of complex mixtures of contaminants.     

The comparative energetics of 'caviomorph' rodents.

The energetics of 11 species of New World hystricognath ('caviomorph') rodents are presented and compared with data from the literature on 19 additional species. Log(10) body mass alone accounts for 94% of the variation in the log(10) basal rate of metabolism in caviomorphs. The residual variation in basal rate is correlated with the stratum on which species live: arboreal species have low basal rates; terrestrial and fossorial species have intermediate basal rates; and aquatic species have high basal rates. When stratum is not included in the analysis, folivores, especially those that are arboreal, have lower basal rates than species with other food habits when combined with log(10) body mass. Small island endemics, all of which are folivores, have basal rates that are 61% of continental species. Log(10) basal rate correlates with family affiliation when combined with log(10) mass, but only if no other factor is included. Therefore, caviomorphs with low basal rates are arboreal, folivorous, live on small islands and belong to the Capromyidae, whereas other character combinations are associated with higher basal rates. These observations demonstrate that the basal rates of caviomorphs reflect many factor interactions. No differences in basal rate were found to reflect climate. Log(10) mass, the only factor to correlate with conductance, accounts for 82% of the variation in log(10) minimal thermal conductance. Mean interspecific body temperature was 36.9 degrees C; it was lowest in aquatic and fossorial species.     

Development of the energetics of muscular exercise with age: Summary of a 30-year study. III. Endogenous and exogenous factors influencing the development of the energetics of skeletal muscles

Differences in the age-related changes in the physical working capacity and the structure of the energy supply of muscular exercise of different powers determined by external (physical education conditions) and internal (gender characteristics) factors are described. Periods of synchronous and asynchronous development of the physical working capacity parameters have been revealed that are characterized by predomination of endogenous or exogenous influences on the processes studied.     

Development of the energetics of muscular exercise with age: Summary of a 30-Year study: IV. The development of the energetics of skeletal muscles depending on the somatotype

The report is based on the results of an 11-year longitudinal study on the age-dependent changes in the muscular working capacity in 7-to 17-year-old boys and girls with different somatotypes. Type-specific features of the development of the energetics of skeletal muscles and sex-related differences in the typological structure of the sample have been found. Somatotype-predisposed differences in the structure of the energy supply of muscular exercise are shown.     

Microbial energetics

An understanding of the mechanisms by which bacteria derive their energy is clearly important for the prediction of growth yields. Bacteria can synthesize ATP by a variety of routes, by fermentation, by oxidative phosphorylation, and possibly by the excretion of metabolic end products. The bacterium Escherichia coli has been studied extensively and a great deal is now known about the different membrane-bound multi-enzyme complexes that are responsible for oxidative phosphorylation. The efficiency of oxidative phosphorylation can vary not only between different bacteria that have adapted to particular ecological niches but also in an individual bacterium grown under different conditions or modified genetically by mutation with respect to its parent. Clearly, the concept that bacteria always grow with maximum thermodynamic efficiency is erroneous and it is important, therefore, to be able to assess the efficiency of energy conversion as well as the biochemical and genetical factors that regulate the physiological expression of energy-yielding reactions if they are to be manipulated by the investigator.     

Folding energetics of ligand binding proteins. I. Theoretical model

Heat capacity curves as obtained from differential scanning calorimetry are an outstanding source for molecular information on protein folding and ligand-binding energetics. However, deconvolution of C(p) data of proteins in the presence of ligands can be compromised by indeterminacies concerning the correct choice of the statistical thermodynamic ensemble. By convent, the assumption of constant free ligand concentration has been used to derive formulae for the enthalpy. Unless the ligand occurs at large excess, this assumption is incorrect. Still the relevant ensemble is the grand canonical ensemble. We derive formulae for both constraints, constancy of total or free ligand concentration and illustrate the equations by application to the typical equilibrium Nx <=> N + x <=> D + x. It is demonstrated that as long as the thermodynamic properties of the ligand can be completely corrected for by performing a reference measurement, the grand canonical approach provides the proper and mathematically significantly simpler choice. We demonstrate on the two cases of sequential or independent ligand-binding the fact, that similar binding mechanisms result in different and distinguishable heat capacity equations. Finally, we propose adequate strategies for DSC experiments as well as for obtaining first estimates of the characteristic thermodynamic parameters, which can be used as starting values in a global fit of DSC data.     

The energetics of intramolecular reactions and enzyme catalysis.

The relative rates of reactions should always be examined by an awareness of differential effects. The magnitude and variation of the relative rates of intramolecular reactions can be rationalized by the differences in entropy and strain energy. The relative rates of enzyme-catalysed reactions are sometimes due to groundstate effects. The beta-lactamase-catalysed hydrolysis of beta-lactam antibiotics may require a unique disposition of catalytic groups owing to an unusual process of bond fission in the four membered ring.     

Respiratory energetics during exercise at high altitude.

The purpose of this study was to assess the effect of high altitude (HA) on work of breathing and external work capacity. On the basis of simultaneous records of esophageal pressure and lung volume, the mechanical power of breathing (Wrs) was measured in four normal subjects during exercise at sea level (SL) and after a 1-mo sojourn at 5,050 m. Maximal exercise ventilation (VEmax) and maximal Wrs were higher at HA than at SL (mean 185 vs. 101 l/min and 129 vs. 40 cal/min, respectively), whereas maximal O2 uptake averaged 2.07 and 3.03 l/min, respectively. In three subjects, the relationship of Wrs to minute ventilation (VE) was the same at SL and HA, whereas, in one individual, Wrs for any given VE was consistently lower at HA. Assuming a mechanical efficiency (E) of 5%, the O2 cost of breathing at HA and SL should amount to 26 and 5.5% of maximal O2 uptake, whereas for E of 20% the corresponding values were 6.5 and 1.4%, respectively. Thus, at HA, Wrs may substantially limit external work unless E is high. Although at SL VEmax did not exceed the critical VE, at which any increase in VE is not useful in terms of body energetics even for E of 5%, at HA VEmax exceeded critical VE even for E of 20%.     

Ecology and energetics of encephalization in hominid evolution.

Hominid evolution is marked by very significant increase in relative brain size. Because relative brain size has been linked to energetic requirements it is possible to look at the pattern of encephalization as a factor in the evolution of human foraging and dietary strategies. Major expansion of the brain is associated with Homo rather than the Hominidae as a whole, and the energetic costs are likely to have forced a prolongation of growth rates and secondary altriciality. It is calculated here that modern human infants have energetic requirements approximately 9% greater than similar size apes due to their large brains. Consideration of energetic costs of brain allow the prediction of growth rates in hominid taxa and an examination of the implications for life-history strategy and foraging behaviour.     

Folding energetics of a multidomain protein, flagellin.

Thermodynamic investigations of flagellin from Salmonella typhimurium and its proteolytic fragments were conducted by differential scanning calorimetry (DSC) and circular dichroism (CD) melting measurements. A new method of analysis for a multi-state transition based on our original theoretical treatment of thermodynamic equations has been developed to analyze those data. The analysis of DSC curves confirmed the three thermodynamic domains of flagellin. The thermodynamic parameters of each domain were revised from those previously reported and the new values of the parameters have a good correlation to the apparent molecular masses of the morphological domains. CD melting measurements at far and near-UV wavelengths showed sequential unfolding of the domains. Therefore, we could reasonably assign the thermodynamically identified domains to the morphological domains. Further analysis of both DSC and CD data provided insights into the folding energetics of the multidomain structure of flagellin. An inner domain (Df1) of flagellin in the filament unfolds through a relatively broad transition, while the two outer domains unfold cooperatively and show sharp transitions. This indicates that the interdomain interactions between Df1 and D2 has different characteristics from the apparently more intimate interactions between D2 and D3. These characteristics suggest that flagellin is organized with relatively flexible domains and rigid domains, which appears to be responsible for the well-regulated assembly mechanism of the bacterial flagellar filament.     

Temperature and the energetics of development in the house cricket (Acheta domesticus)

The influence of rearing temperature on the energetics of development was investigated in house crickets (Acheta domesticus). Crickets raised at 25 degrees C grew slower (0.51 mg d(-1), dry mass basis) and took longer to develop (119 d) but obtained a greater adult body mass (61 mg, dry mass) than crickets reared at 28 degrees C (0.99 mg d(-1), 49 d, 48 mg). Total metabolic energy consumed during development at 25 degrees C (1351 J) was twice that at 28 degrees C (580 J) primarily because of the longer development period, and as a consequence the specific net cost of growth was much greater for crickets reared at 25 degrees C (22.1 kJ g(-1)) than 28 degrees C (11.9 kJ g(-1)).     

The energetics of obesity

Although there is little argument about the state of energy imbalance that produces weight gain, there is considerable argument about the respective role of genetics, diet and physical activity in achieving obesity. In the USA, obesity has increased in the last decades despite a concomitant decrease in total energy and fat intake suggesting that there has been a dramatic drop in total energy expenditure. In this review, we investigated the respective role of resting metabolic rate, post-prandial thermogenesis, and activity energy expenditure in this lower energy output, and provided evidence that physical inactivity is the major contributor. Based on Jean Mayer original observation (Mayer et al., 1954), we hypothesize that there is a level of physical activity below which mechanisms of body mass regulation are impaired. The increasing prevalence of obesity may reflect the fact the majority of the population has fallen below such a level of physical activity. However, a causal relation between physical inactivity and obesity is still difficult to prove, probably because of the lack of longitudinal models to investigate the physiological consequences of inactivity and because the deleterious consequences of sedentary behaviors are essentially deduced from the benefits of exercise training. By using long term strict bed rest as a unique model of inactivity, we provide evidence that inactivity per se indeed disrupts fuel homeostasis and partitions post-absorptive and post-prandial fat use towards storage, thus promoting weight gain in the long term. More research is needed to investigate mechanisms and to determine the minimal physical activity our body has been engineered for by evolution.     

Native-state energetics of a thermostabilized variant of ribonuclease HI.

Escherichia coli RNase HI is a well-characterized model system for protein folding and stability. Controlling protein stability is critical for both natural proteins and for the development of engineered proteins that function under extreme conditions. We have used native-state hydrogen exchange on a variant containing the stabilizing mutation Asp10 to alanine in order to determine its residue-specific stabilities. On average, the DeltaG(unf) value for each residue was increased by 2-3 kcal/mol, resulting in a lower relative population of partially unfolded forms. Though increased in stability by a uniform factor, D10A shows a distribution of stabilities in its secondary structural units that is similar to that of E. coli RNase H, but not the closely related protein from Thermus thermophilus. Hence, the simple mutation used to stabilize the enzyme does not recreate the balance of conformational flexibility evolved in the thermophilic protein.     

Streptavidin-biotin binding energetics

The high affinity energetics in the streptavidin-biotin system provide an excellent model system for studying how proteins balance enthalpic and entropic components to generate an impressive overall free energy for ligand binding. We review here concerted site-directed mutagenesis, biophysical, and computational studies of aromatic and hydrogen bonding interaction energetics between streptavidin and biotin. These results also have provided insight into how streptavidin builds a large activation barrier to dissociation by managing the enthalpic and entropic activation components. Finally, we review recent studies of the biotin dissociation pathway that address the fundamental question of how ligands exit protein binding pockets.