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PubMed1988

Dependence of force, velocity, and O2 consumption on [Ca2+]o in porcine carotid artery.

The relationship between extracellular calcium concentration ([Ca2+]o), isometric force (Fo), unloaded shortening velocity (Vus), and the rate of ATP utilization (JATP) were studied in vascular smooth muscle (VSM) during the steady state of an isometric contraction at 37 degrees C. Experiments were conducted on porcine carotid artery media strip and ring preparations that were stimulated with 109 mM KCl substituted for NaCl. Unloaded shortening velocity was estimated by the "slack" test method. Both Fo and Vus were dependent on [Ca2+]o. Vus at 7.5 mM [Ca2+]o was 1.7 times greater than Vus at 1.6 mM [Ca2+]o. The difference in force at these two Ca2+ concentrations was more variable than Vus, but in general was less than the change in Vus. The rate of ATP utilization was assessed from steady-state measurements of tissue O2 consumption. Increasing [Ca2+]o in the range of 0.15-7.5 mM resulted in an increase in both JATP and Fo. The relation between JATP and Fo was nonlinear with JATP increasing proportionately more than Fo between 1.6 and 7.5 mM Ca2+. The calcium-dependent increase in JATP appears to be primarily related to contractile protein interaction, since the effect of [Ca2+]o on JATP was substantially reduced during stimulation at short muscle lengths (Lmin), where tension development is absent. The economy of tension maintenance was 3.3. times greater when measured in the [Ca2+]o range of 0.15 and 1.6 mM than when measured at 1.6 to 7.5 mM [Ca2+]o. These data indicate that [Ca2+]o may regulate both the number and the rate of cycling of cross bridges in porcine carotid artery.

Adenosine Triphosphate↗
PubMed1997

Effects of increasing times of incomplete cerebral ischemia upon the energy state and lipid peroxidation in the rat.

Different times of incomplete cerebral ischemia (2, 4, 6, 8, 10 and 30 min) were induced by bilateral common carotid artery occlusion in anesthetized rats to evaluate the time course of changes in lipid peroxidation and energy metabolism. Analysis of malondialdehyde (used to assess the levels of lipid peroxidation), ascorbic acid, oxypurines, nucleosides, nicotinic coenzymes and high-energy phosphates, was carried out by high-performance liquid chromatography on neutralized perchloric acid extract of brain tissue. Under the present experimental conditions, malondialdehyde, nicotinic coenzymes and ATP catabolites (oxypurines and nucleosides) were affected by increasing times of ischemia, with respect to control sham-operated rats. In particular, the concentration of malondialdehyde, undetectable in control brains, increased from 1.26 nmol/g wet weight after 2 min of carotid clamping to 13.42 nmol/g wet weight at the end of 30 min of incomplete cerebral ischemia. The presence of oxidative stress was further supported by ascorbic acid depletion, which was particularly significant after 10 and 30 min of incomplete ischemia. Carotid clamping provoked an imbalance between energy production and consumption that was evidenced by a reduction in ATP and GTP concentrations and an increase in ATP degradation products such as AMP, oxypurines and nucleosides. A decrement in the sum of adenine nucleotides and the energy charge potential indicated a progressive malfunctioning of energy-producing metabolic cycles. A possible contribution to such a severe change in energy state might be related to depletion of NAD and NADP, particularly noticeable after the longest incomplete brain ischemia times, that should have provoked a consequent lessening of oxido-reductive reactions. Bilateral carotid clamping causes a significant reduction in brain oxygen and substrate supply that results in inhibition of energy metabolism and triggering of oxygen-radical-induced lipid peroxidation.

Animals↗
PubMed2004

Mechanoenergetic estimation of multiple cross-bridge steps per ATP in a beating heart.

The efficiency from the ventricular O(2) consumption (VO(2)) to the total mechanical energy (TME) generated by ventricular contraction has proved relatively constant at approximately 35%, independent of the loading and contractile conditions in a canine heart. TME is the sum of the external mechanical work for ejecting a stroke volume against the afterload and of the mechanical potential energy for developing ventricular pressure in each beat. The approximately 35% VO(2)-to-TME efficiency indicates an also constant approximately 60% ATP-to-TME efficiency in a beating heart, based on the nominal approximately 60% VO(2)-to-ATP efficiency in the myocardial oxidative phosphorylation. I newly attempted to explain the load-independent approximately 60% ATP-to-TME efficiency by the recently reported approximately 7-10 nm unitary step size and approximately 0.8-1.5 pN unitary force of a cross-bridge (CB) at the molecular level in in vitro motility assays. This single CB behavior suggests that its unitary cycle could generate a mechanical energy of approximately 0.6-1.5x10(-20) J at most. From the nominal free energy of approximately 10x10(-20) J per ATP, the efficiency from one ATP to the CB unitary cycle would then be approximately 6-15%. This low efficiency is only approximately 1/10-1/4 of the approximately 60% ATP-to-TME efficiency at the heart level. This discrepancy suggests that each CB would repeat the unitary cycle at least approximately 4-10 times per ATP to achieve the high constant ATP-to-TME efficiency in a beating heart. This seems to represent a considerable mechanoenergetic advantage of the heart at the integrative heart level as compared to the molecular CB level.

Adenosine Triphosphate↗
PubMed2003

Cardiac and renal mitochondria respond differently to hydrogen peroxide in suckling rats.

BACKGROUND: Overwhelming septicemia with multiple organ failure is one of the main causes of mortality with neonatal surgery. Liver, kidney, and heart are organs for which oxidative metabolism is particularly important. Hydrogen peroxide (H(2)O(2)), a major mediator of sepsis, inhibits liver metabolism. Our aim was to determine the effects of H(2)O(2) on neonatal renal and cardiac oxidative metabolism. MATERIALS AND METHODS: Mitochondria were isolated from the heart and kidney of 11 to 15-day-old rats. Oxygen consumption was measured polarographically in mitochondria incubated with different concentrations of H(2)O(2). State 3 oxygen consumption, which represents maximum mitochondrial oxidative flux, was measured in the presence of adenosine diphosphate. State 4 oxygen consumption, which represents oxygen consumption that is wasted and not used for adenosine triphosphate (ATP) generation, was measured after all adenosine diphosphate was used. beta-Oxidation flux and carnitine palmitoyltransferase I activity were measured radiochemically with increased levels of H(2)O(2). RESULTS: H(2)O(2) impaired state 3 oxygen consumption at all concentrations tested in cardiac and renal mitochondria. H(2)O(2) had no significant effect on heart mitochondrial state 4 oxygen consumption but significantly increased that of kidney. Heart, but not kidney, beta-oxidation flux was inhibited by H(2)O(2). Neither cardiac nor renal carnitine palmitoyltransferase I activity was affected by H(2)O(2). CONCLUSIONS: H(2)O(2) inhibits maximal rates of ATP generation by heart and kidney mitochondria but has a more severe effect on kidney mitochondria because more oxygen is wasted and not used for ATP generation. This decrease in ATP generation may be a factor in the dysfunction of these organs during sepsis.

Adenosine Triphosphate↗
PubMed1997

Proteolytic activity of the ATP-dependent protease HslVU can be uncoupled from ATP hydrolysis.

HslVU is a new Escherichia coli ATP-dependent protease composed of two multimeric complexes: the HslU ATPase and the HslV peptidase. Prior studies indicated that HslVU requires ATP hydrolysis for the cleavage of peptides and proteins. We show here that ATP concentrations that activate hydrolysis of benzyloxycarbonyl-Gly-Gly-Leu-7-amido-4-methylcoumarin are 50-100 fold lower than those necessary for degradation of proteins (e.g. casein). Also, the nonhydrolyzable analogs of ATP, 5'-adenylyl beta, gamma-imidodiphosphate (AMP-PNP) and adenosine 5'-(alpha, beta-methylene)triphosphate, can support peptide hydrolysis, but only after an initial time lag not seen with ATP. This delay decreased at higher temperatures and with higher HslU or HslV concentrations and was eliminated by preincubation of HslU and HslV together. Thus, ATP hydrolysis accelerates the association of HslU and HslV, which occurs slowly with the nonhydrolyzable analog. The addition of KCl stimulated 4-6-fold the peptidase activity with AMP-PNP present and eliminated the time lag, but KCl had no stimulatory effect with ATP. NH4+ and Cs+ had similar effects as K+, but Na+ and Li+ were ineffective. AMP-PNP by itself supported hydrolysis of casein and other polypeptides only 20% as well as ATP, but in the presence of K+, Cs+, or NH4+, AMP-PNP activated casein degradation even better than ATP, although it was not hydrolyzed. In addition, MgCl2, MnCl2, and CaCl2 allowed some peptidase and caseinase activity in the absence of any nucleotide. However, Mn2+ and Ca2+, unlike Mg2+, abolished ATP hydrolysis and prevented further activation by ATP or AMP-PNP. These findings indicate that ATP binding to a high affinity site triggers the formation of an active state capable of peptide cleavage, although ATP hydrolysis facilitates this process. Rapid degradation of proteins requires a distinct state of the enzyme, which is normally reached through ATP hydrolysis at low affinity sites. However, AMP-PNP binding together with K+ can induce a form of HslVU that degrades proteins without energy consumption.

ATP-Dependent Proteases↗
PubMedDate not supplied

Metabolism of round spermatids in the rat: effect of gossypol on the glucose transport.

Low dose of gossypol (5 microM) completely inhibited uptake of 2-deoxy-D-glucose by rat spermatids. With gossypol 2-deoxy-D-glucose transport into spermatids increased curvelinearly for 10 minutes after the start of incubation, but reached a plateau afterwards, whereas without gossypol it continuously increased. The levels of fructose-1,6-bis-phosphate (FBP) and ATP were inversely correlated when the cells were exposed to glucose. However, in the presence of gossypol the levels of ATP and FBP decreased simultaneously. In addition, gossypol at 10 microM stimulated oxygen consumption when lactate was present. These results suggest that gossypol probably inhibits glucose transport into spermatids by lowering the ATP level by uncoupling respiratory chain-linked phosphorylation.

Adenosine Triphosphate↗
PubMed2001

Cardiac energetics during ischaemia and the rationale for metabolic interventions.

Cardiac work is supported by high rates of combustion of carbon fuel and oxygen consumption. Fatty acids are the main fuel for the healthy heart, supplying approximately 60-80% of the energy. The balance of the energy comes from the oxidation of glucose and lactate. ATP is broken down to fuel contractile work. ATP is resynthesized in the mitochondria using energy from the oxidation of fatty acids, glucose, and lactate. Myocardial ischaemia dramatically alters fuel metabolism. Ischaemia occurs when the coronary blood flow is insufficient to supply enough oxygen to combust carbon fuels and resynthesize ATP at the normal rate. During partial reductions in coronary blood flow (30-60% of normal) there is a proportional decrease in the rates of oxygen consumption and production of ATP, and an increase in uptake of glucose by the heart. However, unlike under normal aerobic conditions, the glucose taken up by the ischaemic myocardium is not readily oxidized in the mitochondria, but rather is converted to lactate and there is a switch from uptake of lactate by the heart to lactate production. This causes a dramatic disruption in cell homeostasis: ATP content decreases; there is accumulation of lactate and H+, a fall in intracellular pH and a decrease in contractile work. Paradoxically, the ischaemic tissue continues to derive most of its energy (50-70%) from the oxidation of fatty acids despite there being a high rate of lactate production. This ischaemia-induced disruption of cardiac metabolism can be minimized by metabolic agents that decrease oxidation of fatty acids and increase the rates of combustion of glucose and lactate, resulting in clinical benefit to the ischaemic patient.

Animals↗
PubMed1995

Bioenergetic scaling: metabolic design and body-size constraints in mammals.

The cytosolic phosphorylation ratio ([ATP]/[ADP][P(i)]) in the mammalian heart was found to be inversely related to body mass with an exponent of -0.30 (r = 0.999). This exponent is similar to -0.25 calculated for the mass-specific O2 consumption. The inverse of cytosolic free [ADP], the Gibbs energy of ATP hydrolysis (delta G'ATP), and the efficiency of ATP production (energy captured in forming 3 mol of ATP per cycle along the mitochondrial respiratory chain from NADH to 1/2 O2) were all found to scale with body mass with a negative exponent. On the basis of scaling of the phosphorylation ratio and free cytosolic [ADP], we propose that the myocardium and other tissues of small mammals represent a metabolic system with a higher driving potential (a higher delta G'ATP from the higher [ATP]/[ADP][P(i)]) and a higher kinetic gain [(delta V/Vmax)/delta [ADP]] where small changes in free [ADP] produce large changes in steady-state rates of O2 consumption. From the inverse relationship between mitochondrial efficiency and body size we calculate that tissues of small mammals are more efficient than those of large mammals in converting energy from the oxidation of foodstuffs to the bond energy of ATP. A higher efficiency also indicates that mitochondrial electron transport is not the major site for higher heat production in small mammals. We further propose that the lower limit of about 2 g for adult endotherm body size (bumblebee-bat, Estrucan shrew, and hummingbird) may be set by the thermodynamics of the electron transport chain. The upper limit for body size (100,000-kg adult blue whale) may relate to a minimum delta G'ATP of approximately 55 kJ/mol for a cytoplasmic phosphorylation ratio of 12,000 M-1.

Adenosine Diphosphate↗
PubMed1994

Clofazimine alters the energy metabolism and inhibits the growth rate of a human lung-cancer cell line in vitro and in vivo.

The anti-leprosy drug Clofazimine is known to inhibit respiratory function and hence energy metabolism in yeast and in transformed fibroblasts. The aim of this study was to examine the effect of Clofazimine on the energy metabolism of a chemoresistant human non-small-cell bronchial-carcinoma cell line (WIL) and to determine whether this agent might inhibit the growth rate of this cell line in vitro and in vivo. Oxidative phosphorylation was estimated in vitro by measuring oxygen consumption polarographically and glycolysis was estimated from lactate production. In cells that had been pre-treated with an ATP synthetase inhibitor (oligomycin), the addition of Clofazimine resulted in an increase in oxygen consumption similar to that observed with 2,4-dinitrophenol, a classical inhibitor of oxidative phosphorylation. This inhibition of mitochondrial function was associated with an increase in lactate production. Cellular ATP levels were maintained, possibly indicating a compensatory increase in ATP production via glycolysis. Clofazimine was shown to have a direct cytotoxic effect in vitro with an ID50 of 10.2 microM. When Clofazimine was administered to athymic mice bearing WIL as a subcutaneous xenograft, tumour growth rate was significantly reduced, so that after 3 weeks, tumour size was one third that of controls (p < 0.01). These results suggest that selective inhibition of tumour energy metabolism with agents such as Clofazimine is a potential novel approach to cancer treatment.

Adenosine Diphosphate↗
PubMed1998

The metabolic cost of neural information.

We derive experimentally based estimates of the energy used by neural mechanisms to code known quantities of information. Biophysical measurements from cells in the blowfly retina yield estimates of the ATP required to generate graded (analog) electrical signals that transmit known amounts of information. Energy consumption is several orders of magnitude greater than the thermodynamic minimum. It costs 10(4) ATP molecules to transmit a bit at a chemical synapse, and 10(6)-10(7) ATP for graded signals in an interneuron or a photoreceptor, or for spike coding. Therefore, in noise-limited signaling systems, a weak pathway of low capacity transmits information more economically, which promotes the distribution of information among multiple pathways.

Action Potentials↗
PubMed2006

Significant increase of glycolytic flux in Torulopsis glabrata by inhibition of oxidative phosphorylation.

This study was aimed at increasing the glycolytic flux of the multivitamin-auxotrophic yeast Torulopsis glabrata by disturbing oxidative phosphorylation. We examined two different strategies to impede oxidative phosphorylation. The first strategy was disruption of the activity of the electron transfer chain (ETC), by either of two approaches. One was separately adding, at 10 mg L1, specific inhibitors of complex I (rotenone) or of the bc1 complex (antimycin A) to the culture broth of T. glabrata CCTCC M202019, which resulted in significantly decreased intracellular ATP levels (43% and 27.7%) and significantly increased rates of glucose consumption (qs) and pyruvate production (qp); another approach was breeding a respiratory-deficient mutant RD-16, in which cytochromes aa3 and b in the ETC were deleted after ethidium bromide mutagenesis, to reduce the ETC activity constitutively. The second strategy was inhibiting F0F1-ATP synthase with 0.05 mM oligomycin. Also, a neomycin-resistant mutant with 65% decreased F0F1-ATPase activity was studied. With the two strategies, the specific activity of phosphofructokinase (R2=0.9971), the average specific glucose consumption rate (R2=0.9967) and the average specific pyruvate production rate (R2=0.965) were closely correlated with the intracellular ATP level, all of them being increased at a lower intracellular ATP level.

Adenosine Triphosphate↗
PubMed1993

Myocardial adaptation during acute hibernation: mechanisms of phosphocreatine recovery.

OBJECTIVES: Acute hibernation, defined as a prolonged period of moderately reduced oxygen supply and stable haemodynamic function, results in metabolic adaptation characterised primarily by an increase in phosphocreatine. The mechanism of this increase in phosphocreatine is unknown, but has been postulated to result from either an increase in adenosine triphosphate (ATP) production or a decrease in ATP utilisation under conditions of constant myocardial oxygen consumption (MVO2). These experiments were performed to test the hypotheses that (1) acute hibernation could be modelled in an isolated perfused rat heart exhibiting metabolic adaptation; and (2) recovery of phosphocreatine could be explained by alterations in relative creatine kinase flux during hibernation. METHODS: Nuclear magnetic resonance techniques were used in an isolated, perfused rat heart model of acute hibernation to determine the changes in metabolites and creatine kinase kinetics. A flow reduction from 12.5 to 5.4 ml.min-1 was employed for two hours, followed by reperfusion. RESULTS: Reduction of flow resulted in a stable 44% reduction in rate-pressure product. Phosphocreatine had a significant decrease of 9% within the first 15 minutes of ischaemia, but recovered to control values by the end of ischaemia. ATP and [ADP], although unchanged in the early phase of ischaemia, were progressively reduced during the later phase of ischaemia. Intracellular pH fell from 6.99(0.04) to 6.92(0.03) after 15 minutes of ischaemia with little recovery. Saturation transfer measurements showed stability of the forward flux in the creatine kinase reaction during ischaemia, but a progressive reduction in the calculated reverse flux. CONCLUSIONS: These data show that acute hibernation can be modelled in an isolated perfused heart, exhibiting recovery of phosphocreatine despite progressive reductions in ATP. Metabolic changes during acute hibernation have a phasic response characterised by an early ischaemic phase and a later adaptive phase. There is a time related change in measured creatine kinase flux, consistent with a differential change in either ATP production via an increase in MB creatine kinase isoenzyme or a shift in the activity of mitochondrial v cytosolic creatine kinase, a reduction in ATP utilisation via increased efficiency of ATP utilisation at the myofibril, or a changing contribution of glycolytically produced ATP.

Adenosine Diphosphate↗
PubMed1984

Metabolic bases of excess post-exercise oxygen consumption: a review.

The classical "oxygen debt" hypothesis formulated by Hill and associates in the 1920s was an attempt to link the metabolism of lactic acid with the O2 consumption in excess of resting that occurs after exercise. The O2 debt was hypothesized to represent the oxidation of a minor fraction (1/5) of the lactate formed during exercise, to provide the energy to reconvert the remainder (4/5) of the lactate to glycogen during recovery. In 1933 Margaria et al. modified this hypothesis by distinguishing between initial, fast ("alactacid"), and second, slow ("lactacid"), O2-debt curve components. They hypothesized that the fast phase of the post-exercise O2 consumption curve was due to the restoration of phosphagen (ATP + CP). It is now probable that the original lactic acid explanation of the O2 debt was too simplistic. Numerous studies on several species have provided evidence demonstrating a dissociation between the kinetics of lactate removal and the slow component of the post-exercise VO2. The metabolism of lactate, a readily oxidizable substrate, following exercise appears to be directed primarily toward energy production in mitochondria. The elevated concentration of lactate present at the end of exercise may be viewed as a "reservoir of carbon," which may serve as a source of oxidative ATP production or as a source of carbon skeletons for the synthesis of glucose, glycogen, amino acids, and TCA cycle intermediates. The metabolic basis of the elevated post-exercise VO2 may be understood in terms of those factors which directly or indirectly influence mitochondrial O2 consumption. Included among these factors are catecholamines, thyroxine, glucocorticoids, fatty acids, calcium ions, and temperature. Of these, elevated temperature is perhaps the most important. As no complete explanation of the post-exercise metabolism exists, it is recommended that the term "O2 debt" be used to describe a set of phenomena during recovery from exercise. The terms "alactacid debt" and "lactacid debt," which suggest a mechanism, are inappropriate. Use of alternative terms, e.g., "excess post-exercise oxygen consumption" (EPOC) and "recovery O2," will avoid implication of causality in describing the elevation in metabolic rate above resting levels after exercise.

Amphibians↗
PubMed1999

Role of an ATP-sensitive potassium channel opener, YM934, in mitochondrial energy production in ischemic/reperfused heart.

We examined a possible mechanism of action of an ATP-sensitive potassium (K(ATP)) channel opener, YM934, for the improvement of energy metabolism in hearts subjected to 35-min ischemia and 60-min reperfusion. The treatment with 30 nM YM934 for the final 15 min of preischemia enhanced postischemic recovery of left ventricular developed pressure, attenuated the postischemic rise in left ventricular end-diastolic pressure, and suppressed the release of creatine kinase and ATP metabolites during reperfusion. The treatment also restored myocardial ATP and creatine phosphate contents and attenuated the decrease in mitochondrial oxygen consumption rate during reperfusion. The higher mitochondrial function was also seen in YM934-treated hearts at the end of ischemia. In another set of experiments, myocardial skinned bundles were incubated for 30 min under hypoxic conditions in the presence and absence of YM934, and then mitochondrial oxygen consumption rate was determined. Hypoxia decreased the mitochondrial oxygen consumption rate of skinned bundles to approximately 40% of the prehypoxic value. In contrast, the treatment of skinned bundles with 30 nM YM934 preserved the mitochondrial oxygen consumption rate during hypoxia. The effect of YM934 on the hypoxic skinned bundles was abolished by combined treatment with either the K(ATP) channel blocker glyburide or the mitochondrial K(ATP) channel blocker 5-hydroxydecanoate in a concentration-dependent manner. The results suggest that YM934 is capable of attenuating ischemia/reperfusion injury of isolated perfused hearts due to preservation of mitochondrial function during ischemia, probably through opening of mitochondrial K(ATP) channels.

Adenosine Triphosphate↗
PubMed2003

Effect of NO synthase inhibition on myocardial metabolism during moderate ischemia.

Nitric oxide (NO) is involved in the control of myocardial metabolism. In normoperfused myocardium, NO synthase inhibition shifts myocardial metabolism from free fatty acid (FFA) toward carbohydrate utilization. Ischemic myocardium is characterized by a similar shift toward preferential carbohydrate utilization, although NO synthesis is increased. The importance of NO for myocardial metabolism during ischemia has not been analyzed in detail. We therefore assessed the influence of NO synthase inhibition with N(G)-nitro-l-arginine (l-NNA) on myocardial metabolism during moderate ischemia in anesthetized pigs. In control animals, the increase in left ventricular pressure with l-NNA was mimicked by aortic constriction. Before ischemia, l-NNA decreased myocardial FFA consumption (MV(FFA); P < 0.05), while consumption of carbohydrate and O(2) (MVo(2)) remained constant. ATP equivalents [calculated with the assumption of complete oxidative substrate decomposition (ATP(eq))] decreased with l-NNA (P < 0.05), associated with a decrease of regional myocardial function (P < 0.05). In contrast, aortic constriction had no effect on MV(FFA), while MVo(2) increased (P < 0.05) and ATP(eq) and regional myocardial function remained constant. During ischemia, alterations in myocardial metabolism were similar in control and l-NNA-treated animals: MV(FFA) decreased (P < 0.05) and net lactate consumption was reversed to net lactate production (P < 0.05). Regional myocardial function was decreased (P < 0.05), although more markedly in animals receiving l-NNA (P < 0.05). We conclude that the efficiency of oxidative metabolism was impaired by l-NNA per se, paralleled by impaired regional myocardial function. During ischemia, l-NNA had no effect on myocardial substrate consumption, indicating that NO synthases were no longer effectively involved in the control of myocardial metabolism.

Animals↗
PubMed1987

Myocardial energy production and consumption remain balanced during positive inotropic stimulation when coronary flow is restricted to basal rates in rabbit heart.

The effect on myocardial energy balance of increasing oxygen demand without altering basal myocardial perfusion rate was assessed in isolated, isovolumic, retrograde blood perfused rabbit hearts. Myocardial energy requirements were increased with paired stimulation. The capacity of rapid paired stimulation to increase mechanical energy consumption was demonstrated in the presence of increased perfusion with the rate X pressure product and oxygen consumption increasing 86 and 148%, respectively, compared with control values. In contrast, rapid paired stimulation under constant, basal flow conditions did not alter the rate X pressure product, while oxygen extraction and consumption increased only 40% relative to control. Myocardial ATP, creatine-phosphate, and lactate content were identical under control and constant flow-paired stimulation conditions. The results of this study indicate that no detectable energy imbalance was produced by rapid paired stimulation with flow held constant at basal rates. These results suggest that the myocardium does not increase mechanical energy expenditure in response to inotropic or rate stimulation in the presence of restricted flow reserve and are inconsistent with the concept of "demand-induced" or "relative" myocardial ischemia.

Adenosine Triphosphate↗
PubMed2003

An intrinsic adenylate kinase activity regulates gating of the ABC transporter CFTR.

Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel in the ATP binding cassette (ABC) transporter family. Like other ABC transporters, it can hydrolyze ATP. Yet while ATP hydrolysis influences channel gating, it has long seemed puzzling that CFTR would require this reaction because anions flow passively through CFTR. Moreover, no other ion channel is known to require the large energy of ATP hydrolysis to gate. We found that CFTR also has adenylate kinase activity (ATP + AMP <=> ADP + ADP) that regulates gating. When functioning as an adenylate kinase, CFTR showed positive cooperativity for ATP suggesting its two nucleotide binding domains may dimerize. Thus, channel activity could be regulated by two different enzymatic reactions, ATPase and adenylate kinase, that share a common ATP binding site in the second nucleotide binding domain. At physiologic nucleotide concentrations, adenylate kinase activity, rather than ATPase activity may control gating, and therefore involve little energy consumption.

ATP-Binding Cassette Transporters↗
PubMed1979

Biochemical basis of aroclor 1254 and pesticide toxicity in vitro. 1. Effects on intracellular ATP concentration.

Aroclor 1254 and op'-DDT inhibit lymphocyte mitogenic response to PHA. We use petri dish purified lymphocytes for studying the biochemical basis of chemical toxicity. Aroclor 1254 and DDT decrease lymphocyte intracellular ATP concentration. The inhibitory effect on ATP production is due to the suppression of mitochondrial respiration as judged by decreased oxygen consumption. Lymphocyte glycolysis measured by lactate production is not inhibited by Aroclor 1254 to any significant extent. ATP is required for various biosynthetic reactions following mitogenic stimulation. The inhibition of mitochondrial respiration which leads to decreased ATP concentration may be responsible for Aroclor inhibition of lymphocyte mitogenic response to PHA.

Adenosine Triphosphate↗