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

1997 ◽  
Vol 77 (3) ◽  
pp. 731-758 ◽  
Author(s):  
D. F. Rolfe ◽  
G. C. Brown
Keyword(s):  
Free Energy ◽  
Oxygen Consumption ◽  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Metabolic Rate ◽  
Atp Synthesis ◽  
Standard Metabolic Rate ◽  
Evolutionary Significance ◽  
Proton Leak ◽  
Molecular Origin

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.

ConA induced changes in energy metabolism of rat thymocytes

1992 ◽  
Vol 12 (5) ◽  
pp. 381-386 ◽  
Author(s):  
F. Buttgereit ◽  
M. D. Brand ◽  
M. Müller
Keyword(s):  
Protein Synthesis ◽  
Oxygen Consumption ◽  
Energy Metabolism ◽  
Dna Synthesis ◽  
Atp Synthesis ◽  
Proton Leak ◽  
Ehrlich Ascites ◽  
Activated State ◽  
Ehrlich Ascites Tumour ◽  
Induced Changes

The influence of ConA on the energy metabolism of quiescent rat thymocytes was investigated by measuring the effects of inhibitors of protein synthesis, proteolysis, RNA/DNA synthesis, Na+K+-ATPase, Ca2+-ATPase and mitochondrial ATP synthesis on respiration. Only about 50% of the coupled oxygen consumption of quiescent thymocytes could be assigned to specific processes using two different media. Under these conditions the oxygen is mainly used to drive mitochondrial proton leak and to provide ATP for protein synthesis and cation transport, whereas oxygen consumption to provide ATP for RNA/DNA synthesis and ATP-dependent proteolysis was not measurable. The mitogen ConA produced a persistent increase in oxygen consumption by about 30% within seconds. After stimulation more than 80% of respiration could be assigned to specific processes. The major oxygen consuming processes of ConA-stimulated thymocytes are mitochondrial proton leak, protein synthesis and Na+K+-ATPase with about 20% each of total oxygen consumption, while Ca2+-ATPase and RNA/DNA synthesis contribute about 10% each. Quiescent thymocytes resemble resting hepatocytes in that most of the oxygen consumption remains unexplained. In constrast, the pattern of energy metabolism in stimulated thymocytes is similar to that described for Ehrlich Ascites tumour cells and splenocytes, which may also be in an activated state. Most of the oxygen consumption is accounted for, so the unexplained process(es) in unstimulated cells shut(s) off on stimulation.

ConA induced changes in energy metabolism of rat thymocytes

1992 ◽  
Vol 12 (2) ◽  
pp. 109-114 ◽  
Author(s):  
F. Buttgereit ◽  
M. D. Brand ◽  
M. Müller
Keyword(s):  
Protein Synthesis ◽  
Oxygen Consumption ◽  
Energy Metabolism ◽  
Dna Synthesis ◽  
Atp Synthesis ◽  
Proton Leak ◽  
Ehrlich Ascites ◽  
Activated State ◽  
Ehrlich Ascites Tumour ◽  
Induced Changes

The influence of ConA on the energy metabolism of quiescent rat thymocytes was investigated by measuring the effects of inhibitors of protein synthesis, proteolysis, RNA/DNA synthesis, Na+K+-ATPase, Ca2+-ATPase and mitochondrial ATP synthesis on respiration. Only about 50% of the coupled oxygen consumption of quiescent thymocytes could be assigned to specific processes using two different media. Under these conditions the oxygen is mainly used to drive mitochondrial proton leak and to provide ATP for protein synthesis and cation transport, whereas oxygen consumption to provide ATP for RNA/DNA synthesis and ATP-dependent proteolysis was not measurable. The mitogen ConA produced a persistent increase in oxygen consumption by about 30% within seconds. After stimulation more than 80% of respiration could be assigned to specific processes. The major oxygen consuming processes of ConA-stimulated thymocytes are mitochondrial proton leak, protein synthesis and Na+K+-ATPase with about 20% each of total oxygen consumption, while Ca2+-ATPase and RNA/DNA synthesis contribute about 10% each. Quiescent thymocytes resemble resting hepatocytes in that most of the oxygen consumption remains unexplained. In contrast, the pattern of energy metabolism in stimulated thymocytes is similar to that described for Ehrlich Ascites tumour cells and splenocytes, which may also be in an activated state. Most of the oxygen consumption is accounted for, so the unexplained process(es) in unstimulated cells shut(s) off on stimulation.

scholarly journals Control of respiration and ATP synthesis in mammalian mitochondria and cells

1992 ◽  
Vol 284 (1) ◽  
pp. 1-13 ◽  
Author(s):  
G C Brown
Keyword(s):  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Respiratory Chain ◽  
Atp Synthase ◽  
Energy Charge ◽  
Atp Synthesis ◽  
Basic Mechanism ◽  
Proton Leak ◽  
Control Of Respiration ◽  
Phosphorylation Potential

We have seen that there is no simple answer to the question ‘what controls respiration?’ The answer varies with (a) the size of the system examined (mitochondria, cell or organ), (b) the conditions (rate of ATP use, level of hormonal stimulation), and (c) the particular organ examined. Of the various theories of control of respiration outlined in the introduction the ideas of Chance & Williams (1955, 1956) give the basic mechanism of how respiration is regulated. Increased ATP usage can cause increased respiration and ATP synthesis by mass action in all the main tissues. Superimposed on this basic mechanism is calcium control of matrix dehydrogenases (at least in heart and liver), and possibly also of the respiratory chain (at least in liver) and ATP synthase (at least in heart). In many tissues calcium also stimulates ATP usage directly; thus calcium may stimulate energy metabolism at (at least) four possible sites, the importance of each regulation varying with tissue. Regulation of multiple sites may occur (from a teleological point of view) because: (a) energy metabolism is branched and thus proportionate regulation of branches is required in order to maintain constant fluxes to branches (e.g. to proton leak or different ATP uses); and/or (b) control over fluxes is shared by a number of reactions, so that large increases in flux requires stimulation at multiple sites because each site has relatively little control. Control may be distributed throughout energy metabolism, possibly due to the necessity of minimizing cell protein levels (see Brown, 1991). The idea that energy metabolism is regulated by energy charge (as proposed by Atkinson, 1968, 1977) is misleading in mammals. Neither mitochondrial ATP synthesis nor cellular ATP usage is a unique function of energy charge as AMP is not a significant regulator (see for example Erecinska et al., 1977). The near-equilibrium hypothesis of Klingenberg (1961) and Erecinska & Wilson (1982) is partially correct in that oxidative phosphorylation is often close to equilibrium (apart from cytochrome oxidase) and as a consequence respiration and ATP synthesis are mainly regulated by (a) the phosphorylation potential, and (b) the NADH/NAD+ ratio. However, oxidative phosphorylation is not always close to equilibrium, at least in isolated mitochondria, and relative proximity to equilibrium does not prevent the respiratory chain, the proton leak, the ATP synthase and ANC having significant control over the fluxes. Thus in some conditions respiration rate correlates better with [ADP] than with phosphorylation potential, and may be relatively insensitive to mitochondrial NADH/NAD+ ratio.(ABSTRACT TRUNCATED AT 400 WORDS)

Mitochondrial cytochrome c oxidase and control of energy metabolism: measurements in suspensions of isolated mitochondria

2014 ◽  
Vol 117 (12) ◽  
pp. 1424-1430 ◽  
Author(s):  
David F. Wilson ◽  
David K. Harrison ◽  
Andrei Vinogradov
Keyword(s):  
Oxygen Consumption ◽  
Energy Metabolism ◽  
Cytochrome C ◽  
Oxidative Phosphorylation ◽  
Respiratory Rate ◽  
Cytochrome C Oxidase ◽  
Energy State ◽  
Atp Synthesis ◽  
Oxygen Depletion ◽  
High Energy

Cytochrome c oxidase is the enzyme responsible for oxygen consumption by mitochondrial oxidative phosphorylation and coupling site 3 of oxidative phosphorylation. In this role it determines the cellular rate of ATP synthesis by oxidative phosphorylation and is the key to understanding how energy metabolism is regulated. Four electrons are required for the reduction of oxygen to water, and these are provided by the one-electron donor, cytochrome c. The rate of oxygen consumption (ATP synthesis) is dependent on the fraction of cytochrome c reduced (fred), oxygen pressure (pO2), energy state ([ATP]/[ADP][Pi]), and pH. In coupled mitochondria (high energy state) and pO2 >60 torr, the rate increases in an exponential-like fashion with increasing fred. When the dependence on fred is fitted to the equation rate = a(fred)b, a decreased from 100 to near 20, and b increased from 1.3 to 4 as the pH of the medium increased from 6.5 to 8.3. During oxygen depletion from the medium fred progressively increases and the rate of respiration decreases. The respiratory rate falls to ½ (P50) by about 1.5 torr, at which point fred is substantially increased. The metabolically relevant dependence on pO2 is obtained by correcting for the increase in fred, in which case the P50 is 12 torr. Adding an uncoupler of oxidative phosphorylation eliminates the dependence of the cytochrome c oxidase activity on pH and energy state. The respiratory rate becomes proportional to fred and the P50 decreases to less than 1 torr.

Standard metabolic rate and preferred body temperatures in some Australian pythons

1998 ◽  
Vol 46 (4) ◽  
pp. 317 ◽  
Author(s):  
Gavin S. Bedford ◽  
Keith A. Christian
Keyword(s):  
Oxygen Consumption ◽  
Body Temperature ◽  
Metabolic Rate ◽  
Thermal Sensitivity ◽  
Standard Metabolic Rate ◽  
Allometric Equations ◽  
Metabolic Rates ◽  
Body Temperatures ◽  
Daily Cycle ◽  
Preferred Body Temperature

Pythons have standard metabolic rates and preferred body temperatures that are lower than those of most other reptiles. This study investigated metabolic rates and preferred body temperatures of seven taxa of Australian pythons. We found that Australian pythons have particularly low metabolic rates when compared with other boid snakes, and that the metabolic rates of the pythons did not change either seasonally or on a daily cycle. Preferred body temperatures do vary seasonally in some species but not in others. Across all species and seasons, the preferred body temperature range was only 4.9˚C. The thermal sensitivity (Q10) of oxygen consumption by pythons conformed to the established range of between 2 and 3. Allometric equations for the pooled python data at each of the experimental temperatures gave an equation exponent of 0.72–0.76, which is similar to previously reported values. By having low preferred body temperatures and low metabolic rates, pythons appear to be able to conserve energy while still maintaining a vigilant ‘sit and wait’ predatory existence. These physiological attributes would allow pythons to maximise the time they can spend ‘sitting and waiting’ in the pursuit of prey.

Top-down control analysis of the effect of temperature on ectotherm oxidative phosphorylation

2004 ◽  
Vol 287 (4) ◽  
pp. R794-R800 ◽  
Author(s):  
M. E. Chamberlin
Keyword(s):  
Oxygen Consumption ◽  
Membrane Potential ◽  
Oxidative Phosphorylation ◽  
Substrate Oxidation ◽  
The State ◽  
Proton Leak ◽  
Control Analysis ◽  
Top Down ◽  
Temperature Ranges ◽  
Oxidation System

Top-down control and elasticity analysis was conducted on mitochondria isolated from the midgut of the tobacco hornworm ( Manduca sexta) to assess how temperature affects oxidative phosphorylation in a eurythermic ectotherm. Oxygen consumption and protonmotive force (measured as membrane potential in the presence of nigericin) were monitored at 15, 25, and 35°C. State 4 respiration displayed a Q10 of 2.4–2.7 when measured over two temperature ranges (15–25°C and 25–35°C). In state 3, the Q10s for respiration were 2.0 and 1.7 for the lower and higher temperature ranges, respectively. The kinetic responses (oxygen consumption) of the substrate oxidation system, proton leak, and phosphorylation system increased as temperature rose, although the proton leak and substrate oxidation system showed the greatest thermal sensitivity. Whereas there were temperature-induced changes in the activities of the oxidative phosphorylation subsystems, there was no change in the state 4 membrane potential and little change in the state 3 membrane potential. Top-down control analysis revealed that control over respiration did not change with temperature. In state 4, control of respiration was shared nearly equally by the proton leak and the substrate oxidation system, whereas in state 3 the substrate oxidation system exerted over 90% of the control over respiration. The proton leak and phosphorylation system account for <10% of the temperature-induced change in the state 3 respiration rate. Therefore, when the temperature is changed, the state 3 respiration rate is altered primarily because of temperature's effect on the substrate oxidation system.

scholarly journals Body size and temperature effects on standard metabolic rate for determining metabolic scope for activity of the polychaete Hediste (Nereis) diversicolor

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5675 ◽  
Author(s):  
Helena Lopes Galasso ◽  
Marion Richard ◽  
Sébastien Lefebvre ◽  
Catherine Aliaume ◽  
Myriam D. Callier
Keyword(s):  
Oxygen Consumption ◽  
Body Size ◽  
Metabolic Rate ◽  
Growth Rates ◽  
Reaction Rate ◽  
Specific Growth ◽  
Standard Metabolic Rate ◽  
Metabolic Scope ◽  
Specific Growth Rates ◽  
Arrhenius Temperature

Considering the ecological importance and potential value of Hediste diversicolor, a better understanding of its metabolic rate and potential growth rates is required. The aims of this study are: (i) to describe key biometric relationships; (ii) to test the effects of temperature and body size on standard metabolic rate (as measure by oxygen consumption) to determine critical parameters, namely Arrhenius temperature (TA), allometric coefficient (b) and reaction rate; and (iii) to determine the metabolic scope for activity (MSA) of H. diversicolor for further comparison with published specific growth rates. Individuals were collected in a Mediterranean lagoon (France). After 10 days of acclimatization, 7 days at a fixed temperature and 24 h of fasting, resting oxygen consumption rates (VO2) were individually measured in the dark at four different temperatures (11, 17, 22 and 27 °C) in worms weighing from 4 to 94 mgDW (n = 27 per temperature). Results showed that DW and L3 were the most accurate measurements of weight and length, respectively, among all the metrics tested. Conversion of WW (mg), DW (mg) and L3 (mm) were quantified with the following equations: DW = 0.15 × WW, L3 = 0.025 × TL(mm) + 1.44 and DW = 0.8 × L33.68. Using an equation based on temperature and allometric effects, the allometric coefficient (b) was estimated at 0.8 for DW and at 2.83 for L3. The reaction rate (VO2) equaled to 12.33 µmol gDW−1 h−1 and 0.05 µmol mm L3−1 h−1 at the reference temperature (20 °C, 293.15 K). Arrhenius temperature (TA) was 5,707 and 5,664 K (for DW and L3, respectively). Metabolic scope for activity ranged from 120.1 to 627.6 J gDW−1 d−1. Predicted maximum growth rate increased with temperature, with expected values of 7–10% in the range of 15–20 °C. MSA was then used to evaluate specific growth rates (SGR) in several experiments. This paper may be used as a reference and could have interesting applications in the fields of aquaculture, ecology and biogeochemical processes.

The Physiological Significance of Mitochondrial Proton Leak in Animal Cells and Tissues

1997 ◽  
Vol 17 (1) ◽  
pp. 9-16 ◽  
Author(s):  
David F. S. Rolfe ◽  
Martin D. Brand
Keyword(s):  
Reactive Oxygen Species ◽  
Metabolic Rate ◽  
Animal Species ◽  
Standard Metabolic Rate ◽  
Physiological Significance ◽  
Proton Leak ◽  
Oxygen Species ◽  
Animal Cells ◽  
Wide Range ◽  
Leak Pathway

Mitochondrial proton leak is an important component of cellular metabolism in animals and may account for as much as one quarter to one third of the Standard Metabolic Rate of the rat. The activity of the proton leak pathway is different in a wide range of animal species and in different thyroid states. Such differences imply some function for proton leak and candidates for this function include thermogenesis, protection against reactive oxygen species, endowment of metabolic sensitivity and maintenance of carbon fluxes.

Contribution of mitochondrial proton leak to skeletal muscle respiration and to standard metabolic rate

1996 ◽  
Vol 271 (4) ◽  
pp. C1380-C1389 ◽  
Author(s):  
D. F. Rolfe ◽  
M. D. Brand
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Rate ◽  
Respiration Rate ◽  
Rat Hepatocytes ◽  
Standard Metabolic Rate ◽  
Proton Leak ◽  
Rat Skeletal Muscle ◽  
Isolated Rat Hepatocytes ◽  
Mitochondrial Inner Membrane

We have tested the hypothesis that the leak of protons across the mitochondrial inner membrane (proton leak) is a significant contributor to standard metabolic rate (SMR). We found that proton leak accounts for around one-half of the resting respiration rate of perfused rat skeletal muscle. Proton leak is known to make a significant (26%) contribution to the resting respiration rate of isolated rat hepatocytes (M. D. Brand, L.-F. Chien, E. K. Ainscow, D. F. S. Rolfe, and R. K. Porter. Biochim. Biophys. Acta 1187: 132-139, 1994). If the importance of proton leak in these isolated and perfused systems is similar to its importance in vivo, then using literature values for the contribution of liver and skeletal muscle to SMR, we can calculate that proton leak in liver and skeletal muscle alone accounts for 11-26% (mean 20%) of the SMR of the rat. If proton leak activity in the other tissues of the rat is similar to that in liver cells, then the contribution of proton leak to rat SMR would be 16-31% (mean 25%).

Sign in / Sign up

Export Citation Format

Share Document