Relation between phosphate metabolites and oxygen consumption of heart in vivo

1989 ◽  
Vol 256 (1) ◽  
pp. H265-H274 ◽  
Author(s):  
L. A. Katz ◽  
J. A. Swain ◽  
M. A. Portman ◽  
R. S. Balaban
Keyword(s):  
Oxygen Consumption ◽  
Atp Hydrolysis ◽  
Respiratory Control ◽  
Creatine Phosphate ◽  
Canine Heart ◽  
Hydrolysis Products ◽  
Threefold Increase ◽  
Cooperativity Effects

The relation between induced increases in cardiac work and phosphate metabolites was investigated in the canine heart in vivo to evaluate the role of ATP hydrolysis products, ADP and inorganic phosphate (Pi), in the control of myocardial oxygen consumption (MVO2). In these studies, myocardial blood flow and oxygen consumption were simultaneously measured with the 31P-nuclear magnetic resonance (NMR)-detected phosphate metabolites. Three protocols were used to increase myocardial work: pacing, epinephrine, and phenylephrine infusions. When these protocols were used, no or only slight changes in myocardial ATP, Pi, and creatine phosphate were observed with a greater than threefold increase in MVO2. The calculated intracellular free Mg concentration, ADP, and pH were also only slightly affected by these increases in work. These data indicate that a simple model involving the feedback of cytosolic ADP and Pi to the mitochondria regulating respiration is inadequate to explain respiratory control in vivo. These data suggest that some other parameters or cooperativity effects involving the phosphate metabolites must play a role in the feedback between respiration and work in the heart in vivo.

scholarly journals The relationship between initial creatine phosphate breakdown and recovery oxygen consumption for a single isometric tetanus of the frog sartorius muscle at 20 degrees C.

1979 ◽  
Vol 73 (2) ◽  
pp. 159-174 ◽  
Author(s):  
M Mahler
Keyword(s):  
Oxygen Consumption ◽  
Time Course ◽  
Atp Hydrolysis ◽  
Creatine Phosphate ◽  
Sartorius Muscle ◽  
Exothermic Reactions ◽  
Rate Of Oxygen Consumption ◽  
The Relationship ◽  
Frog Sartorius

A previous paper (Mahler, M. 1978 J. Gen. Physiol. 71:559--580) describes the time-course of the suprabasal rate of oxygen consumption (delta QO2) in the sartorius muscle of R. pipiens after isometric tetani of 0.1--1.0 s at 20 degrees C. To test whether these were the responses to impulse changes in the rate of ATP hydrolysis, we compared the total suprabasal oxygen consumption during recovery (delta[O2]) with the amount of ATP hydrolyzed during a contraction, measured indirectly as the decrease in creatine phosphate (delta[CP]O). If suprabasal ATP hydrolysis during recovery is negligible in comparison with that during contraction, delta[CP]0/delta[O2] should approximate the P:O2 ratio for oxidative metabolism, which has an expected value of 6.1--6.5. We found: formula; see text. We conclude that in this muscle at 20 degrees C: (a) after a tetanus of 0.2--1.0 s, delta QO2(t) can be considered the response to an impulse increase in the rate of ATP hydrolysis; (b) the reversal during recovery of unidentified exothermic reactions occurring during the contraction (Woledge, R. C. 1971. Prog. Biophys. Mol. Biol. 22:39--74) can be coupled to an ATP hydrolysis that is at most a small fraction of delta[CP]0; (c) the pooled mean for delta[CP]0/delta[O2], 6.58 +/- 0.55, sets an experimental lower bound for the P:O2 ratio in vivo.

scholarly journals Effect of muscle action and metabolic strain on oxidative metabolic responses in human skeletal muscle

1999 ◽  
Vol 87 (5) ◽  
pp. 1768-1775 ◽  
Author(s):  
C. A. Combs ◽  
A. H. Aletras ◽  
R. S. Balaban
Keyword(s):  
Free Energy ◽  
Atp Hydrolysis ◽  
Tibialis Anterior Muscle ◽  
Respiratory Control ◽  
Oxidative Capacity ◽  
Resonance Spectroscopy ◽  
Muscle Action ◽  
Pooled Data ◽  
Muscle Actions

A recent report suggests that differences in aerobic capacity exist between concentric and eccentric muscle action in human muscle (T. W. Ryschon, M. D. Fowler, R. E. Wysong, A. R. Anthony, and R. S. Balaban. J. Appl. Physiol. 83: 867–874, 1997). This study compared oxidative response, in the form of phosphocreatine (PCr) resynthesis rates, with matched levels of metabolic strain (i.e., changes in ADP concentration or the free energy of ATP hydrolysis) in tibialis anterior muscle exercised with either muscle action in vivo ( n = 7 subjects). Exercise was controlled and metabolic strain measured by a dynamometer and 31P-magnetic resonance spectroscopy, respectively. Metabolic strain was varied to bring cytosolic ADP concentration up to 55 μM or decrease the free energy of ATP hydrolysis to −55 kJ/mol with no change in cytoplasmic pH. PCr resynthesis rates after exercise ranged from 31.9 to 462.5 and from 21.4 to 405.4 μmol PCr/s for concentric and eccentric action, respectively. PCr resynthesis rates as a function of metabolic strain were not significantly different between muscle actions ( P > 0.40), suggesting that oxidative capacity is dependent on metabolic strain, not muscle action. Pooled data were found to more closely conform to previous biochemical measurements when a term for increasing oxidative capacity with metabolic strain was added to models of respiratory control.

scholarly journals NO modulates myocardial O2consumption in the nonhuman primate: an additional mechanism of action of amlodipine

1999 ◽  
Vol 276 (6) ◽  
pp. H2069-H2075 ◽  
Author(s):  
Paul R. Forfia ◽  
Xiaoping Zhang ◽  
Delvin R. Knight ◽  
Andrew H. Smith ◽  
Christopher P. A. Doe ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Nonhuman Primate ◽  
Myocardial Oxygen Consumption ◽  
Channel Blocker ◽  
Tissue Response ◽  
Canine Heart ◽  
Additional Mechanism

Recent evidence from our laboratory and others suggests that nitric oxide (NO) is a modulator of in vivo and in vitro oxygen consumption in the murine and canine heart. Therefore, the goal of our study was twofold: to determine whether NO modulates myocardial oxygen consumption in the nonhuman primate heart in vitro and to evaluate whether the seemingly cardioprotective actions of amlodipine may involve an NO-mediated mechanism. Using a Clark-type O2 electrode, we measured oxygen consumption in cynomologous monkey heart at baseline and after increasing doses of S-nitroso- N-acetylpenicillamine (SNAP; 10−7–10−4M), bradykinin (10−7–10−4M), ramiprilat (10−7–10−4M), and amlodipine (10−7–10−5M). SNAP (−38 ± 5.8%), bradykinin (−19 ± 3.9%), ramiprilat (−28 ± 2.3%), and amlodipine (−23 ± 4.5%) each caused significant ( P < 0.05) reductions in myocardial oxygen consumption at their highest dose. Preincubation of tissue with nitro-l-arginine methyl ester (10−4 M) blunted the effects of bradykinin (−5.4 ± 3.2%), ramiprilat (−4.8 ± 5.0%), and amlodipine (−5.3 ± 5.0%) but had no effect on the tissue response to SNAP (−38 ± 5.8%). Our results indicate that NO can reduce oxygen consumption in the primate myocardium in vitro, and they support a role for the calcium-channel blocker amlodipine as a modulator of myocardial oxygen consumption via a kinin-NO mediated mechanism.

Interaction of Oxidative Phosphorylation and Work in the Heart, In Vivo

Physiology ◽  
1989 ◽  
Vol 4 (6) ◽  
pp. 215-218
Author(s):  
RS Balaban ◽  
FW Heineman
Keyword(s):  
Oxidative Phosphorylation ◽  
Control Mechanism ◽  
Atp Hydrolysis ◽  
Atp Production ◽  
Hydrolysis Products ◽  
The Subject ◽  
Regulatory Sites

The mechanism that balances the rates of myocardial ATP production and use is the subject of this brief review. Recent in vivo data suggest that this control mechanism does not depend solely on the concentrations of ATP hydrolysis products. Other potential regulatory sites are currently being investigated.

scholarly journals In vivo FRET analyses reveal a role of ATP hydrolysis–associated conformational changes in human P-glycoprotein

2020 ◽  
Vol 295 (15) ◽  
pp. 5002-5011 ◽  
Author(s):  
Ryota Futamata ◽  
Fumihiko Ogasawara ◽  
Takafumi Ichikawa ◽  
Atsushi Kodan ◽  
Yasuhisa Kimura ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Drug Transport ◽  
Atp Hydrolysis ◽  
Hek293 Cells ◽  
Atp Binding ◽  
Binding Domains ◽  
P Glycoprotein ◽  
Atp Binding And Hydrolysis

P-glycoprotein (P-gp; also known as MDR1 or ABCB1) is an ATP-driven multidrug transporter that extrudes various hydrophobic toxic compounds to the extracellular space. P-gp consists of two transmembrane domains (TMDs) that form the substrate translocation pathway and two nucleotide-binding domains (NBDs) that bind and hydrolyze ATP. At least two P-gp states are required for transport. In the inward-facing (pre-drug transport) conformation, the two NBDs are separated, and the two TMDs are open to the intracellular side; in the outward-facing (post-drug transport) conformation, the NBDs are dimerized, and the TMDs are slightly open to the extracellular side. ATP binding and hydrolysis cause conformational changes between the inward-facing and the outward-facing conformations, and these changes help translocate substrates across the membrane. However, how ATP hydrolysis is coupled to these conformational changes remains unclear. In this study, we used a new FRET sensor that detects conformational changes in P-gp to investigate the role of ATP binding and hydrolysis during the conformational changes of human P-gp in living HEK293 cells. We show that ATP binding causes the conformational change to the outward-facing state and that ATP hydrolysis and subsequent release of γ-phosphate from both NBDs allow the outward-facing state to return to the original inward-facing state. The findings of our study underscore the utility of using FRET analysis in living cells to elucidate the function of membrane proteins such as multidrug transporters.

Nitric oxide modulates oxygen consumption by arteriolar walls in rat skeletal muscle

2005 ◽  
Vol 289 (6) ◽  
pp. H2673-H2679 ◽  
Author(s):  
Masahiro Shibata ◽  
Shigeru Ichioka ◽  
Akira Kamiya
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
Phosphorescence Quenching ◽  
Arterial Blood ◽  
No Release ◽  
Vessel Walls

To study the role of nitric oxide (NO) in regulating oxygen consumption by vessel walls, the oxygen consumption rate of arteriolar walls in rat cremaster muscle was measured in vivo during flow-induced vasodilation and after inhibiting NO synthesis. The oxygen consumption rate of arteriolar walls was calculated based on the intra- and perivascular Po2 values measured by phosphorescence quenching laser microscopy. The perivascular Po2 value of the arterioles during vasodilation was significantly higher than under control conditions, although the intravascular Po2 values under both conditions were approximately the same. Inhibition of NO synthesis, on the other hand, caused a significant increase in arterial blood pressure and a significant decrease in arteriolar diameter. Inhibition of NO synthesis also caused a significant decrease in both the intra- and perivascular Po2 values of the arterioles. Inhibition of NO synthesis increased the oxygen consumption rate of the vessel walls by 42%, whereas enhancement of flow-induced NO release decreased it by 34%. These results suggest that NO plays an important role not only as a regulator of peripheral vascular tone but also as a modulator of tissue oxygenation by reducing oxygen consumption by vessel walls. In addition, enhancement of NO release during exercise may facilitate efficient oxygen supply to the surrounding high metabolic tissue.

scholarly journals Cdc6 ATPase activity disengages Cdc6 from the pre-replicative complex to promote DNA replication

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
FuJung Chang ◽  
Alberto Riera ◽  
Cecile Evrin ◽  
Jingchuan Sun ◽  
Huilin Li ◽  
...  
Keyword(s):  
Dna Replication ◽  
Atpase Activity ◽  
Atp Hydrolysis ◽  
S Phase ◽  
G1 Phase ◽  
Helicase Loading ◽  
Mcm Helicase

To initiate DNA replication, cells first load an MCM helicase double hexamer at origins in a reaction requiring ORC, Cdc6, and Cdt1, also called pre-replicative complex (pre-RC) assembly. The essential mechanistic role of Cdc6 ATP hydrolysis in this reaction is still incompletely understood. Here, we show that although Cdc6 ATP hydrolysis is essential to initiate DNA replication, it is not essential for MCM loading. Using purified proteins, an ATPase-defective Cdc6 mutant ‘Cdc6-E224Q’ promoted MCM loading on DNA. Cdc6-E224Q also promoted MCM binding at origins in vivo but cells remained blocked in G1-phase. If after loading MCM, Cdc6-E224Q was degraded, cells entered an apparently normal S-phase and replicated DNA, a phenotype seen with two additional Cdc6 ATPase-defective mutants. Cdc6 ATP hydrolysis is therefore required for Cdc6 disengagement from the pre-RC after helicase loading to advance subsequent steps in helicase activation in vivo.

Letters to the Editor

1998 ◽  
Vol 275 (2) ◽  
pp. H726-H729
Author(s):  
J. A. L. Jeneson ◽  
M. J. Kushmerick ◽  
H. V. Westerhoff
Keyword(s):  
Oxygen Consumption ◽  
Steady State ◽  
Western Blot ◽  
Northern Blot ◽  
Adenine Nucleotide ◽  
Respiratory Control ◽  
High Energy ◽  
High Energy Phosphates ◽  
Adenine Nucleotide Translocator

The following is the abstract of the article discussed in the subsequent letter: Portman, Michael A., Yun Xiao, Ying Song, and Xue-Han Ning. Expression of adenine nucleotide translocator parallels maturation of respiratory control in heart in vivo. Am. J. Physiol. 273 ( Heart Circ. Physiol. 42): H1977–H1983, 1997.—Changes in the relationship between myocardial high-energy phosphates and oxygen consumption in vivo occur during development, implying that the mode of respiratory control undergoes maturation. We hypothesized that these maturational changes in sheep heart are paralleled by alterations in the adenine nucleotide translocator (ANT), which are in turn related to changes in the expression of this gene. Increases in myocardial oxygen consumption (MV˙o 2) were induced by epinephrine infusion in newborn (0–32 h, n = 6) and mature sheep (30–32 days, n = 6), and high-energy phosphates were monitored with 31P nuclear magnetic resonance. Western blot analyses for the ANT1 and the β-subunit of F1-adenosinetriphosphatase (ATPase) were performed in these hearts and additional ( n = 9 total per group) as well as in fetal hearts (130–132 days of gestation, n = 5). Northern blot analyses were performed to assess for changes in steady-state RNA transcripts for these two genes. Kinetic analyses for the31P spectra data revealed that the ADP-MV˙o 2 relationship for the newborns conformed to a Michaelis-Menten model but that the mature data did not conform to first- or second-order kinetic control of respiration through ANT. Maturation from fetal to mature was accompanied by a 2.5-fold increase in ANT protein (by Western blot), with no detectable change in β-F1-ATPase. Northern blot data show that steady-state mRNA levels for ANT and β-F1-ATPase increased ∼2.5-fold from fetal to mature. These data indicate that 1) respiratory control pattern in the newborn is consistent with a kinetic type regulation through ANT, 2) maturational decreases in control through ANT are paralleled by specific increases in ANT content, and 3) regulation of these changes in ANT may be related to increases in steady-state transcript levels for its gene.

scholarly journals Insights into the regulatory function of the ɛ subunit from bacterial F-type ATP synthases: a comparison of structural, biochemical and biophysical data

Open Biology ◽  
2018 ◽  
Vol 8 (5) ◽  
pp. 170275 ◽  
Author(s):  
Alexander Krah ◽  
Mariel Zarco-Zavala ◽  
Duncan G. G. McMillan
Keyword(s):  
Atp Hydrolysis ◽  
Structural Data ◽  
Regulatory Function ◽  
Storage Unit ◽  
Energy Storage Unit ◽  
Change Mechanism ◽  
Hairpin Conformation ◽  
Atp Synthases

ATP synthases catalyse the formation of ATP, the most common chemical energy storage unit found in living cells. These enzymes are driven by an electrochemical ion gradient, which allows the catalytic evolution of ATP by a binding change mechanism. Most ATP synthases are capable of catalysing ATP hydrolysis to varying degrees, and to prevent wasteful ATP hydrolysis, bacteria and mitochondria have regulatory mechanisms such as ADP inhibition. Additionally, ɛ subunit inhibition has also been described in three bacterial systems, Escherichia coli , Bacillus PS3 and Caldalkalibacillus thermarum TA2.A1. Previous studies suggest that the ɛ subunit is capable of undergoing an ATP-dependent conformational change from the ATP hydrolytic inhibitory ‘extended’ conformation to the ATP-induced non-inhibitory ‘hairpin’ conformation. A recently published crystal structure of the F 1 domain of the C. thermarum TA2.A1 F 1 F o ATP synthase revealed a mutant ɛ subunit lacking the ability to bind ATP in a hairpin conformation. This is a surprising observation considering it is an organism that performs no ATP hydrolysis in vivo , and appears to challenge the current dogma on the regulatory role of the ɛ subunit. This has prompted a re-examination of present knowledge of the ɛ subunits role in different organisms. Here, we compare published biochemical, biophysical and structural data involving ɛ subunit-mediated ATP hydrolysis regulation in a variety of organisms, concluding that the ɛ subunit from the bacterial F-type ATP synthases is indeed capable of regulating ATP hydrolysis activity in a wide variety of bacteria, making it a potentially valuable drug target, but its exact role is still under debate.

Relationship of intracellular creatine concentration and uptake to muscle mass in vivo

1978 ◽  
Vol 235 (5) ◽  
pp. C199-C203 ◽  
Author(s):  
W. W. Hofmann ◽  
J. Butte ◽  
H. A. Leon
Keyword(s):  
Isometric Exercise ◽  
Major Change ◽  
Creatine Phosphate ◽  
Control Mechanisms ◽  
Relationship Of ◽  
Developing Muscle ◽  
Hydrolysis Of

Attempts have been made to evaluate the role of intracellular creatine in conditions leading to increased or decreased amounts of contractile protein in rat skeletal muscles. Resting concentrations of intracellular creatine ([Cr]i) and creatine phosphate ([CrP]i) were compared in gastrocnemius and soleus muscles with those immediately after a 20-s tetanic stimulation. The hydrolysis of creatine phosphate was the same after heavily and lightly loaded contractions, suggesting that hypertrophy of isometric exercise is not mediated by creatine. With atrophy after denervation or interruption of sciatic axoplasmic flow [Cr]i also remained unchanged, though [CrP]i and the rate of Cr uptake fell after denervation. The major change in adult red and white muscle bulk with unaltered [Cr]i suggests that the Cr sensitivity found by others in developing muscle in vitro has been supplemented or replaced by other control mechanisms.

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