scholarly journals Relationships between the neuronal sodium/potassium pump and energy metabolism. Effects of K+, Na+, and adenosine triphosphate in isolated brain synaptosomes.

1990 ◽  
Vol 95 (4) ◽  
pp. 591-616 ◽  
Author(s):  
M Erecińska ◽  
F Dagani
Keyword(s):  
Oxidative Phosphorylation ◽  
Adenosine Triphosphate ◽  
Lactate Production ◽  
Atp Synthesis ◽  
Adenosine Monophosphate ◽  
Direct Stimulation ◽  
Secondary Importance ◽  
Atp Production ◽  
Moving Force ◽  
Brain Synaptosomes

The relationships between Na/K pump activity and adenosine triphosphate (ATP) production were determined in isolated rat brain synaptosomes. The activity of the enzyme was modulated by altering [K+]e, [Na+]i, and [ATP]i while synaptosomal oxygen uptake and lactate production were measured simultaneously. KCl increased respiration and glycolysis with an apparent Km of about 1 mM which suggests that, at the [K+]e normally present in brain, 3.3-4 mM, the pump is near saturation with this cation. Depolarization with 6-40 mM KCl had negligible effect on ouabain-sensitive O2 uptake indicating that at the voltages involved the activity of the Na/K ATPase is largely independent of membrane potential. Increases in [Na+]i by addition of veratridine markedly enhanced glycoside-inhibitable respiration and lactate production. Calculations of the rates of ATP synthesis necessary to support the operation of the pump showed that greater than 90% of the energy was derived from oxidative phosphorylation. Consistent with this: (a) the ouabain-sensitive Rb/O2 ratio was close to 12 (i.e., Rb/ATP ratio of 2); (b) inhibition of mitochondrial ATP synthesis by Amytal resulted in a decrease in the glycoside-dependent rate of 86Rb uptake. Analyses of the mechanisms responsible for activation of the energy-producing pathways during enhanced Na and K movements indicate that glycolysis is predominantly stimulated by increase in activity of phosphofructokinase mediated via a rise in the concentrations of adenosine monophosphate [AMP] and inorganic phosphate [Pi] and a fall in the concentration of phosphocreatine [PCr]; the main moving force for the elevation in mitochondrial ATP generation is the decline in [ATP]/[ADP] [Pi] (or equivalent) and consequent readjustments in the ratio of the intramitochondrial pyridine nucleotides [( NAD]m/[NADH]m). Direct stimulation of pyruvate dehydrogenase by calcium appears to be of secondary importance. It is concluded that synaptosomal Na/K pump is fueled primarily by oxidative phosphorylation and that a fall in [ATP]/[ADP][Pi] is the chief factor responsible for increased energy production.

Modeling the effects of hypoxia on ATP turnover in exercising muscle

1992 ◽  
Vol 73 (2) ◽  
pp. 737-742 ◽  
Author(s):  
P. G. Arthur ◽  
M. C. Hogan ◽  
D. E. Bebout ◽  
P. D. Wagner ◽  
P. W. Hochachka
Keyword(s):  
Oxygen Consumption ◽  
Metabolic Control ◽  
Lactate Production ◽  
Atp Synthesis ◽  
Atp Production ◽  
Atp Turnover ◽  
Model Based ◽  
The Face ◽  
Energetic State ◽  
Atp Supply

Most models of metabolic control concentrate on the regulation of ATP production and largely ignore the regulation of ATP demand. We describe a model, based on the results of Hogan et al. (J. Appl. Physiol. 73: 728–736, 1992), that incorporates the effects of ATP demand. The model is developed from the premise that a unique set of intracellular conditions can be measured at each level of ATP turnover and that this relationship is best described by energetic state. Current concepts suggest that cells are capable of maintaining oxygen consumption in the face of declines in the concentration of oxygen through compensatory changes in cellular metabolites. We show that these compensatory changes can cause significant declines in ATP demand and result in a decline in oxygen consumption and ATP turnover. Furthermore we find that hypoxia does not directly affect the rate of anaerobic ATP synthesis and associated lactate production. Rather, lactate production appears to be related to energetic state, whatever the PO2. The model is used to describe the interaction between ATP demand and ATP supply in determining final ATP turnover.

Ca2+ activation of heart mitochondrial oxidative phosphorylation: role of the F0/F1-ATPase

2000 ◽  
Vol 278 (2) ◽  
pp. C423-C435 ◽  
Author(s):  
Paul R. Territo ◽  
Vamsi K. Mootha ◽  
Stephanie A. French ◽  
Robert S. Balaban
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthesis ◽  
High Energy ◽  
Ruthenium Red ◽  
Maximal Effect ◽  
Production Rates ◽  
Atp Production ◽  
The Matrix

Ca2+ has been postulated as a cytosolic second messenger in the regulation of cardiac oxidative phosphorylation. This hypothesis draws support from the well-known effects of Ca2+ on muscle activity, which is stimulated in parallel with the Ca2+-sensitive dehydrogenases (CaDH). The effects of Ca2+ on oxidative phosphorylation were further investigated in isolated porcine heart mitochondria at the level of metabolic driving force (NADH or Δψ) and ATP production rates (flow). The resulting force-flow (F-F) relationships permitted the analysis of Ca2+ effects on several putative control points within oxidative phosphorylation, simultaneously. The F-F relationships resulting from additions of carbon substrates alone provided a model of pure CaDH activation. Comparing this curve with variable Ca2+ concentration ([Ca2+]) effects revealed an approximate twofold higher ATP production rate than could be explained by a simple increase in NADH or Δψ via CaDH activation. The half-maximal effect of Ca2+ at state 3 was 157 nM and was completely inhibited by ruthenium red (1 μM), indicating matrix dependence of the Ca2+ effect. Arsenate was used as a probe to differentiate between F0/F1-ATPase and adenylate translocase activity by a futile recycling of ADP-arsenate within the matrix, catalyzed by the F0/F1-ATPase. Ca2+increased the ADP arsenylation rate more than twofold, suggesting a direct effect on the F0/F1-ATPase. These results suggest that Ca2+ activates cardiac aerobic respiration at the level of both the CaDH and F0/F1-ATPase. This type of parallel control of both intermediary metabolism and ATP synthesis may provide a mechanism of altering ATP production rates with minimal changes in the high-energy intermediates as observed in vivo.

scholarly journals Studies of energy-linked reactions. Net synthesis of adenosine triphosphate by isolated adenosine triphosphate synthase preparations: a role for lipoic acid and unsaturated fatty acids

1976 ◽  
Vol 160 (3) ◽  
pp. 809-812 ◽  
Author(s):  
D E Griffiths
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Oxidative Phosphorylation ◽  
Adenosine Triphosphate ◽  
Atp Synthase ◽  
Lipoic Acid ◽  
Adenosine Triphosphatase ◽  
Unsaturated Fatty Acids ◽  
Atp Synthesis ◽  
Substrate Level

ATP synthase preparations [complex V, proton-translocatin ATPase (adenosine triphosphatase) and oligomycin-sensitive ATPase] contain stoicheiometric amounts of lipoic acid residues (up to 6mol of lipoic acid/mol of ATPase complex) and catalyse net ATP synthesis in an uncoupler-and oligomycin-sensitive reaction utilizing dihydrolipoate, oleoyl-CoA and oleic acid, or in a reaction utilizing oleoyl-S-lipoate. The terminal reactions of oxidative phosphorylation are thus analogous to those of substrate-level phosphorylation.

scholarly journals Role of Plant Cell Conditioned Medium in the Phenotypic Expression of Nitrogenase Activity of Rhizobium trifolii Strain T1

1980 ◽  
Vol 33 (5) ◽  
pp. 613 ◽  
Author(s):  
Minocher Reporter ◽  
Mary L Skotnicki ◽  
Barry G Rolfe
Keyword(s):  
Oxidative Phosphorylation ◽  
Conditioned Medium ◽  
Plant Cell ◽  
Nitrogenase Activity ◽  
Phenotypic Expression ◽  
Atp Synthesis ◽  
Atp Production ◽  
Cell Conditioned Medium

The influence of substances from a conditioned medium of cultured plant cells on nitrogenase activity, respiration and ATP synthesis was investigated in R. tri/olii strain Tl. Nitrogenase activity in strain Tl was dependent on the addition of the plant cell conditioned medium. Studies showed that the initial effects of the plant substances on rhizobial cells was to increase their respiration rate and ATP production. Mutants of strain Tl which were uncoupled in their oxidative phosphorylation, were also tested. However, the plant factors had no effect on respiration and ATP synthesis and also failed to elicit in vitro nitrogenase activity in these mutants. It is proposed that these plant factors act by increasing the efficiency of oxidative phosphorylation, making more ATP available, and thus stimulating nitrogenase activity of R. tri/olii cells.

Age-related changes in ATP-producing pathways in human skeletal muscle in vivo

2005 ◽  
Vol 99 (5) ◽  
pp. 1736-1744 ◽  
Author(s):  
Ian R. Lanza ◽  
Douglas E. Befroy ◽  
Jane A. Kent-Braun
Keyword(s):  
Skeletal Muscle ◽  
Oxidative Phosphorylation ◽  
Atp Synthesis ◽  
Older Men ◽  
Oxidative Capacity ◽  
Glycolytic Flux ◽  
Synthesis Rate ◽  
Anaerobic Glycolysis ◽  
Atp Production ◽  
Age Related

Energy for muscle contractions is supplied by ATP generated from 1) the net hydrolysis of phosphocreatine (PCr) through the creatine kinase reaction, 2) oxidative phosphorylation, and 3) anaerobic glycolysis. The effect of old age on these pathways is unclear. The purpose of this study was to examine whether age may affect ATP synthesis rates from these pathways during maximal voluntary isometric contractions (MVIC). Phosphorus magnetic resonance spectroscopy was used to assess high-energy phosphate metabolite concentrations in skeletal muscle of eight young (20–35 yr) and eight older (65–80 yr) men. Oxidative capacity was assessed from PCr recovery after a 16-s MVIC. We determined the contribution of each pathway to total ATP synthesis during a 60-s MVIC. Oxidative capacity was similar across age groups. Similar rates of ATP synthesis from PCr hydrolysis and oxidative phosphorylation were observed in young and older men during the 60-s MVIC. Glycolytic flux was higher in young than older men during the 60-s contraction ( P < 0.001). When expressed relative to the overall ATP synthesis rate, older men relied on oxidative phosphorylation more than young men ( P = 0.014) and derived a smaller proportion of ATP from anaerobic glycolysis ( P < 0.001). These data demonstrate that although oxidative capacity was unaltered with age, peak glycolytic flux and overall ATP production from anaerobic glycolysis were lower in older men during a high-intensity contraction. Whether this represents an age-related limitation in glycolytic metabolism or a preferential reliance on oxidative ATP production remains to be determined.

Targeting Dinitrophenol to Mitochondria: Limitations to the Development of a Self-limiting Mitochondrial Protonophore

2006 ◽  
Vol 26 (3) ◽  
pp. 231-243 ◽  
Author(s):  
Frances H. Blaikie ◽  
Stephanie E. Brown ◽  
Linda M. Samuelsson ◽  
Martin D. Brand ◽  
Robin A. J. Smith ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Membrane Potential ◽  
Oxidative Phosphorylation ◽  
Atp Synthesis ◽  
Proton Leak ◽  
Protonmotive Force ◽  
Inner Membrane ◽  
Atp Production ◽  
Mitochondrial Inner Membrane ◽  
Predominant Component

The protonmotive force (Δp) across the mitochondrial inner membrane drives ATP synthesis. In addition, the energy stored in Δp can be dissipated by proton leak through the inner membrane, contributing to basal metabolic rate and thermogenesis. Increasing mitochondrial proton leak pharmacologically should decrease the efficiency of oxidative phosphorylation and counteract obesity by enabling fatty acids to be oxidised with decreased ATP production. While protonophores such as 2,4-dinitrophenol (DNP) increase mitochondrial proton leak and have been used to treat obesity, a slight increase in DNP concentration above the therapeutically effective dose disrupts mitochondrial function and leads to toxicity. Therefore we set out to develop a less toxic protonophore that would increase proton leak significantly at high Δp but not at low Δp. Our design concept for a potential self-limiting protonophore was to couple the DNP moiety to the lipophilic triphenylphosphonium (TPP) cation and this was achieved by the preparation of 3-(3,5-dinitro-4-hydroxyphenyl)propyltriphenylphosphonium methanesulfonate (MitoDNP). TPP cations accumulate within mitochondria driven by the membrane potential (Δψ), the predominant component of Δp. Our hypothesis was that MitoDNP would accumulate in mitochondria at high Δψ where it would act as a protonophore, but that at lower Δψ the accumulation and uncoupling would be far less. We found that MitoDNP was extensively taken into mitochondria driven by Δψ. However MitoDNP did not uncouple mitochondria as judged by its inability to either increase respiration rate or decrease Δψ. Therefore MitoDNP did not act as a protonophore, probably because the efflux of deprotonated MitoDNP was inhibited.

scholarly journals Editorial for Special Issue “Plant Mitochondria”

2018 ◽  
Vol 19 (12) ◽  
pp. 3849 ◽  
Author(s):  
Nicolas Taylor
Keyword(s):  
Oxidative Phosphorylation ◽  
Adenosine Triphosphate ◽  
Plant Mitochondria ◽  
Atp Synthesis ◽  
Special Issue ◽  
Primary Function

The primary function of mitochondria is respiration, where catabolism of substrates is coupled to adenosine triphosphate (ATP) synthesis via oxidative phosphorylation (OxPhos). [...]

scholarly journals Substrate- and Calcium-Dependent Differential Regulation of Mitochondrial Oxidative Phosphorylation and Energy Production in the Heart and Kidney

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 131
Author(s):  
Xiao Zhang ◽  
Namrata Tomar ◽  
Sunil M. Kandel ◽  
Said H. Audi ◽  
Allen W. Cowley ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Respiration ◽  
Atp Synthesis ◽  
Heart Mitochondria ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Inhibitory Effects ◽  
Atp Production ◽  
Calcium Dependent ◽  
Palmitoyl Carnitine ◽  
Regulatory Effects

Mitochondrial dehydrogenases are differentially stimulated by Ca2+. Ca2+ has also diverse regulatory effects on mitochondrial transporters and other enzymes. However, the consequences of these regulatory effects on mitochondrial oxidative phosphorylation (OxPhos) and ATP production, and the dependencies of these consequences on respiratory substrates, have not been investigated between the kidney and heart despite the fact that kidney energy requirements are second only to those of the heart. Our objective was, therefore, to elucidate these relationships in isolated mitochondria from the kidney outer medulla (OM) and heart. ADP-induced mitochondrial respiration was measured at different CaCl2 concentrations in the presence of various respiratory substrates, including pyruvate + malate (PM), glutamate + malate (GM), alpha-ketoglutarate + malate (AM), palmitoyl-carnitine + malate (PCM), and succinate + rotenone (SUC + ROT). The results showed that, in both heart and OM mitochondria, and for most complex I substrates, Ca2+ effects are biphasic: small increases in Ca2+ concentration stimulated, while large increases inhibited mitochondrial respiration. Furthermore, significant differences in substrate- and Ca2+-dependent O2 utilization towards ATP production between heart and OM mitochondria were observed. With PM and PCM substrates, Ca2+ showed more prominent stimulatory effects in OM than in heart mitochondria, while with GM and AM substrates, Ca2+ had similar biphasic regulatory effects in both OM and heart mitochondria. In contrast, with complex II substrate SUC + ROT, only inhibitory effects on mitochondrial respiration was observed in both the heart and the OM. We conclude that the regulatory effects of Ca2+ on mitochondrial OxPhos and ATP synthesis are biphasic, substrate-dependent, and tissue-specific.

Sign in / Sign up

Export Citation Format

Share Document