Energy Metabolism of the Skeletal Muscle of Genetically Dystrophic Hamster

1972 ◽  
Vol 50 (5) ◽  
pp. 550-556 ◽  
Author(s):  
Naranjan S. Dhalla ◽  
Margaret Fedelesova ◽  
Ivan Toffler
Keyword(s):  
Energy Metabolism ◽  
Skeletal Muscles ◽  
Energy Production ◽  
Creatine Phosphokinase ◽  
Adenine Nucleotides ◽  
Creatine Phosphate ◽  
High Energy ◽  
Dystrophic Muscle ◽  
Glycerophosphate Dehydrogenase ◽  
Glucose 6 Phosphate Dehydrogenase

The hind leg skeletal muscles of about 215-day-old genetically dystrophic hamsters (BIO strain 14.6) were found to contain subnormal concentrations of creatine phosphate, ATP, total adenine nucleotides, and NAD+ in comparison with those from the control animals. On the other hand, the levels of lactate, NADH, and NADPH were elevated without any significant changes in pyruvate, AMP, ADP, and NADP+ in the dystrophic muscle. The ratios of ATP/ADP and ATP/AMP were decreased and those of lactate/pyruvate, NADH/NAD+, and NADPH/NADP+ were increased in the dystrophic muscle. There are a number of similarities between the dystrophic and asphyxiated muscles with respect to energy metabolism; however, the possibility is not ruled out at present that the hypoxic-like changes in energy metabolism of the dystrophic muscle are due to mechanisms other than oxygen lack. The activity of glucose-6-phosphate dehydrogenase was increased whereas the activities of α-glycerophosphate dehydrogenase, glyceraldehyde phosphate dehydrogenase, lactate dehydrogenase, myokinase, and creatine phosphokinase were decreased in the dystrophic muscle. On the basis of our earlier and present results it is suggested that changes in the high energy phosphate stores in the genetically dystrophic hamster muscle are due to defects in both the processes of energy production and utilization.

Impaired energy metabolism in rat myocardium during phosphate depletion

1982 ◽  
Vol 242 (6) ◽  
pp. F699-F704 ◽  
Author(s):  
N. Brautbar ◽  
R. Baczynski ◽  
C. Carpenter ◽  
S. Moser ◽  
P. Geiger ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Adenine Nucleotides ◽  
Creatine Phosphate ◽  
Inorganic Phosphorus ◽  
High Energy ◽  
Deficient Diet ◽  
Myocardial Energetics ◽  
Phosphate Depletion ◽  
Myocardial Biopsies ◽  
Mitochondrial Capacity

The effects of phosphate depletion (PD) of 4, 8, and 12 wk duration on myocardial energy metabolism were studied in rats fed a phosphate-deficient diet and compared with rats pair-fed a normal phosphate diet. Myocardial biopsies were examined for high-energy phosphate bonds. The results show that PD causes a significant reduction in myocardial concentration of inorganic phosphorus at 4 wk of PD and creatine phosphate at 8 wk of PD, while adenine nucleotides were significantly reduced only after 12 wk of PD. The changes in cellular inorganic phosphorus and creatine phosphate displayed a significant correlation with serum phosphorus levels. Mitochondrial respiration was impaired early in PD. Total cellular, mitochondrial, and myofibrillar creatine kinase activities were significantly reduced at 4 wk of PD and fell further at 8 and 12 wk. These data show that chronic PD is associated with reduced mitochondrial capacity to produce ATP, impaired transport via the creatine phosphate shuttle, and reduced myofibrillar ability to utilize ATP. These abnormalities indicate that all steps of myocardial energetics are impaired in PD and provide the molecular basis for the altered myocardial function seen in PD.

scholarly journals Reductions in mitochondrial O2 consumption and preservation of high-energy phosphate levels after simulated ischemia in chronic hibernating myocardium

2009 ◽  
Vol 297 (1) ◽  
pp. H223-H232 ◽  
Author(s):  
Qingsong Hu ◽  
Gen Suzuki ◽  
Rebeccah F. Young ◽  
Brian J. Page ◽  
James A. Fallavollita ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Adenine Nucleotides ◽  
Creatine Phosphate ◽  
High Energy ◽  
Atp Depletion ◽  
Hibernating Myocardium ◽  
Wall Thickening ◽  
High Energy Phosphates ◽  
Simulated Ischemia

We performed the present study to determine whether hibernating myocardium is chronically protected from ischemia. Myocardial tissue was rapidly excised from hibernating left anterior descending coronary regions (systolic wall thickening = 2.8 ± 0.2 vs. 5.4 ± 0.3 mm in remote myocardium), and high-energy phosphates were quantified by HPLC during simulated ischemia in vitro (37°C). At baseline, ATP (20.1 ± 1.0 vs. 26.7 ± 2.1 μmol/g dry wt, P < 0.05), ADP (8.1 ± 0.4 vs. 10.3 ± 0.8 μmol/g, P < 0.05), and total adenine nucleotides (31.2 ± 1.3 vs. 40.1 ± 2.9 μmol/g, P < 0.05) were depressed compared with normal myocardium, whereas total creatine, creatine phosphate, and ATP-to-ADP ratios were unchanged. During simulated ischemia, there was a marked attenuation of ATP depletion (5.6 ± 0.9 vs. 13.7 ± 1.7 μmol/g at 20 min in control, P < 0.05) and mitochondrial respiration [145 ± 13 vs. 187 ± 11 ng atoms O2·mg protein−1·min−1 in control (state 3), P < 0.05], whereas lactate accumulation was unaffected. These in vitro changes were accompanied by protection of the hibernating heart from acute stunning during demand-induced ischemia. Thus, despite contractile dysfunction at rest, hibernating myocardium is ischemia tolerant, with reduced mitochondrial respiration and slowing of ATP depletion during simulated ischemia, which may maintain myocyte viability.

scholarly journals A temporal dissociation of energy liberation and high energy phosphate splitting during shortening in frog skeletal muscles.

1976 ◽  
Vol 68 (1) ◽  
pp. 13-27 ◽  
Author(s):  
J A Rall ◽  
E Homsher ◽  
A Wallner ◽  
W F Mommaerts
Keyword(s):  
Stimulus Pattern ◽  
Skeletal Muscles ◽  
Energy Production ◽  
Time Course ◽  
Rana Pipiens ◽  
High Energy ◽  
Energy Liberation ◽  
High Energy Phosphate ◽  
Contracting Muscle ◽  
Mechanical Measurements

Measurements of the time course of high energy phosphate splitting and energy liberation were performed on rapidly shortening Rana pipiens skeletal muscles. In muscles contracting 30 times against small loads (less the 0.02P), the ratio of explained heat + work (H + W) (calculated from the measured high energy phosphate splitting) to observed H + W (from myothermal and mechanical measurements) was 0.68 +/- 0.08 and is in agreement with results obtained in isometric tetani of R. pipiens skeletal muscle. In lightly afterloaded muscles which were tetanized for 0.6a and whose metabolism was arrested at 3.0 s after the beginning of stimulation, a similar ratio of explained H + W to observed H + W was obtained. However, in identical contractions in which metabolism was arrested at 0.5-0.75 s after the beginning of stimulation, the ratio of explained H + W to observed H + W declined significantly to values ranging from 0.15 to 0.40. These results suggest that rapid shortening at the beginning of contraction induces a delay between energy production and measurable high energy phosphate splitting. This interpretation was tested and confirmed in experiments in which one muscle of a pair contracted isometrically while the other contracted against a small afterload. The afterload and stimulus pattern were arranged so that at the time metabolism was arrested, 0.5 s after the beginning of stimulation, the total energy production by both muscles was the same. Chemical analysis revealed that the isotonically contracting muscle spilt only 25% as much high energy phosphate as did the isometrically contracting muscle.

Anaplerotic effects of propionate on oxidations of acetate and long-chain fatty acids

1996 ◽  
Vol 270 (6) ◽  
pp. H2197-H2203 ◽  
Author(s):  
A. J. Liedtke ◽  
T. Hacker ◽  
B. Renstrom ◽  
S. H. Nellis
Keyword(s):  
Fatty Acids ◽  
Energy Metabolism ◽  
Adenine Nucleotides ◽  
Creatine Phosphate ◽  
Coronary Perfusion ◽  
Acid Activation ◽  
Long Chain Fatty Acids ◽  
Myocardial Substrate ◽  
Long Chain ◽  
Chain Fatty Acids

Studies were performed to test the influence of propionate as a competing myocardial substrate on acetate and palmitate metabolism in reperfused pig hearts after an exposure of mild-to-moderate regional ischemia. Experiments were conducted in intact, working pig hearts (n = 10) using an extracorporeal coronary perfusion technique. Half the animals received 2 mM propionate selectively into the anterior descending (LAD) perfusate. Perfusion conditions in the LAD circulation were divided into three intervals: an aerobic, preischemic period (0–20 min); an ischemic period affected by a 60% reduction in LAD flow (20–60 min); and an aerobic, postischemic period (60–100 min). Steady-state infusions of (1(–14)C) acetate and [9, 10(-3)H] palmitate were begun at 60 min perfusion to monitor metabolism during reperfusion. Propionate had no effect on oxidation of acetate except for a slight delay in CO2 appearance. Propionate significantly suppressed oxidation of long-chain fatty acids (-38 delta %, P < 0.018), which was not explained by a selective scavenging of CoA units or carnitine by propionate, which might otherwise enhance fatty acid activation, transfer, or oxidation. Propionate by indirect estimates had no apparent effect on glucose metabolism. Propionate-treated hearts, despite shifts in substrate preference, were not further compromised in energy metabolism as levels of creatine phosphate and adenine nucleotides were comparable to control hearts. Recovery of regional mechanical function was also comparable between groups but incompletely, with respect to preischemic performance, compatible with myocardial stunning. The data show in reperfused myocardium that propionate is capable of altering the preferred use of fatty acids, but that anaplerotic entry of carbon units during this reperfusion interval was sufficient to prevent a selective imbalance of energy metabolism or deficit in mechanical recovery.

Effect of hyperventilation on dynamics of cerebral energy metabolism

1975 ◽  
Vol 228 (6) ◽  
pp. 1862-1867 ◽  
Author(s):  
K Kogure ◽  
R Busto ◽  
A Matsumoto ◽  
P Scheinberg ◽  
OM Reinmuth
Keyword(s):  
Energy Metabolism ◽  
Closed System ◽  
Energy Production ◽  
Energy Charge ◽  
High Energy ◽  
Utilization Rate ◽  
High Energy Phosphates ◽  
High Energy Phosphate ◽  
Cerebral Energy Metabolism ◽  
Extreme Degree

Hypocapnia of moderate and extreme degree (Paco2 21.1 and 13.5 torr, respectively)was induced by hyperventilation in rats subjected to the closed system of Lowry inorder to evaluate the effects on utilization rate of cerebral energy metabolites. The tissue levels of high-energy phosphates and calculated intracellular pH did not change, whereas glucose, pyruvate, and lactate increased significantly. The La/Pyratio and NADH/NAD-+ RATIO BOTH INCREASED IN PROPORTION TO THE DEGREE OF HYPOCAPNIA.Utilization rates of glucose, glycogen, and ATP were all significantly reduced by hypocapnia, whereas the utilization rate of phosphocreatine was increased. The rate oftotal high-energy phosphate use was also diminished in proportion to the degree of hypocapnia. The constant value of the energy charge (0.94 plus or minus 0.01) indicates that the energy production rate might also be reduced by hyperventilation; thus the intermediate metabolics and substrates increased. It is concluded that extreme hypocapnia reduces the rate of cerebral energy metabolism significantly.

Influence of elevated muscle temperature on metabolism during intense, dynamic exercise

1996 ◽  
Vol 271 (5) ◽  
pp. R1251-R1255 ◽  
Author(s):  
M. A. Febbraio ◽  
M. F. Carey ◽  
R. J. Snow ◽  
C. G. Stathis ◽  
M. Hargreaves
Keyword(s):  
Degradation Products ◽  
Adenine Nucleotides ◽  
Plasma Catecholamines ◽  
Lactate Concentration ◽  
Muscle Metabolism ◽  
Creatine Phosphate ◽  
High Energy ◽  
Cycle Ergometer ◽  
Muscle Temperature ◽  
Ammonia Accumulation

This study examined the effects of elevated muscle temperature on muscle metabolism during exercise. Seven active but untrained men completed two cycle ergometer trials for 2 min at a workload estimated to require 115% maximal oxygen uptake (VO2) either without pretreatment (CT) or after having their thigh wrapped in a heating blanket for 60 min before exercise (HT). HT increased (P < 0.01) muscle temperature (Tm) and resulted in a difference in Tm between the two trials before (delta = 1.9 +/- 0.1 degrees C, P < 0.01) and after exercise (delta = 0.6 +/- 0.2 degree C, P < 0.05). HT did not affect rectal temperature or plasma catecholamines. In addition, these parameters were not different between CT and HT either before or after exercise. No differences in resting intramuscular concentrations of the adenine nucleotides (ATP, ADP, AMP) or their degradation products (inosine 5'-monophosphate, ammonia), lactate, glycogen, creatine phosphate, or creatine were observed between HT and CT. During exercise, the magnitude of ATP degradation and inosine 5'-monophosphate and ammonia accumulation was higher (P < 0.05) in HT compared with CT. Although preexercise concentrations of glycogen and lactate were not different between the two trials, postexercise lactate concentration was higher (P < 0.05) and glycogen lower (P < 0.05) in HT compared with CT. In addition, net muscle glycogen use was higher (P < 0.05) in HT. It is concluded that an elevated Tm per se increases muscle glycogenolysis, glycolysis, and high-energy phosphate degradation during exercise. These alterations may be the result of an increased rate of ATP turnover associated with the exercise and/or changes in the anaerobic/aerobic contribution to ATP resynthesis.

scholarly journals Effect of Dihydroergocristine on Energy Metabolism Studied in the Isolated Perfused Rat Brain Affected by Ischemia and in Neuroblastoma Cells Deprived of Oxygen and Glucose

1984 ◽  
Vol 4 (4) ◽  
pp. 610-614 ◽  
Author(s):  
A. Rachman ◽  
L. Kellmann ◽  
J. Krieglstein
Keyword(s):  
Energy Metabolism ◽  
Rat Brain ◽  
Energy State ◽  
Cell Metabolism ◽  
Neuroblastoma Cells ◽  
Creatine Phosphate ◽  
High Energy ◽  
High Energy Phosphates ◽  
Isolated Perfused Rat Brain

The effect of dihydroergocristine on energy metabolism was studied in the isolated perfused rat brain affected by ischemia and in cultivated C-1300 neuroblastoma cells deprived of oxygen and glucose. Creatine phosphate, ATP, ADP, AMP, glucose, glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, pyruvate, and lactate were measured enzymatically. After a perfusion period of 30 min, the cortex of the isolated perfused rat brain exhibited an energy state not different from that in vivo. Dihydroergocristine added to the perfusion medium (5 μmol/L) did not influence these substrate levels under normal perfusion conditions. However, this drug was able to retard the breakdown of high-energy phosphates during ischemia and to accelerate the restoration of the energy state during the postischemic reperfusion period. The perfusion rate was not changed by the drug, and therefore it was assumed that dihydroergocristine could act directly on cell metabolism. This view was supported by the results obtained from experiments using cultivated N-2a neuroblastoma cells. These cells were incubated in a buffered salt solution deprived of glucose and oxygen for 15 min. Under these conditions, dihydroergocristine (2 μmol/L) added to the incubation medium caused changes in the concentrations of the high-energy phosphates similar to those in the isolated brain preparation: It increased the ATP concentration and decreased the ADP concentration significantly.

Inhibition of Collagen- or Thrombin-Induced Shape Change of Rabbit Platelets

1975 ◽  
Author(s):  
J. F. Mustard ◽  
R. L. Kinlough-Rathbone ◽  
H. J. Reimers ◽  
D. W. Perry ◽  
M. A. Packham
Keyword(s):  
Salicylic Acid ◽  
Creatine Phosphokinase ◽  
Light Transmission ◽  
Shape Change ◽  
Adenine Nucleotides ◽  
Creatine Phosphate ◽  
Partial Inhibition ◽  
Rabbit Platelets ◽  
Induced Aggregation ◽  
Platelet Shape

With suspensions of washed rabbit platelets, EGTA inhibits collagen- or thrombin-induced aggregation but does not inhibit shape change caused by these agents. Addition of apyrase or creatine phosphate/creatine phosphokinase (CP/CPK) to a suspension of washed platelets reduces the extent of collagen-induced aggregation but does not inhibit shape change. Combinations of EGTA with apyrase, CP/CPK, acetyl salicylic acid (ASA) (500 μM) or sulfinpyrazone (300 μM) inhibit collagen-induced shape change. Apyrase and ASA together also inhibit collagen-induced shape change. None of these combinations of inhibitors inhibits thrombin-induced shape change completely, although apyrase or CP/CPK cause partial inhibition. With thrombin-degranulated platelets, collagen induces shape change and a small increase in light transmission. This effect of collagen is inhibited by ASA but not by CP/CPK. The addition of collagen to ASA-treated platelets causes platelet shape change although aggregation does not occur. Addition of collagen to a mixture of thrombin-degranulated and ASA-treated platelets results in shape change and aggregation. It seems likely that endoperoxides formed by the thrombin-degranulated platelets in response to collagen cause shape change and aggregation of the ASA-treated platelets which are unable to form endoperoxides. These observations demonstrate that collagen-induced shape change of rabbit platelets involves two different mechanisms, one of which is inhibited by CP/CPK (and hence is probably caused by released ADP) and one which is inhibited by ASA (and may involve endoperoxide formation). Although thrombin can induce shape change by releasing ADP, it can also induce shape change through a mechanism which is independent of adenine nucleotides release and is not inhibited by ASA.

L-type Ca2+ channel and Na+/Ca2+ exchange inhibitors reduce Ca2+ accumulation in reperfused skeletal muscle

1996 ◽  
Vol 80 (4) ◽  
pp. 1263-1269 ◽  
Author(s):  
D. G. Welsh ◽  
M. I. Lindinger
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Blood Cells ◽  
Contractile Function ◽  
Adenine Nucleotides ◽  
High Energy ◽  
Ischemia And Reperfusion ◽  
Tension Recovery ◽  
Contractile Recovery ◽  
White Gastrocnemius

It is known that extracellular Ca2+ accumulates within skeletal muscle after prolonged periods of ischemia and reperfusion. In this study, we determined whether the L-type Ca2+ channel and the Na+/Ca2+ exchanger mediated Ca2+ influx and whether Ca2+ accumulation limited the metabolic and contractile recovery of reperfused skeletal muscle. Contracting rat hindlimbs (1-Hz twitch) exposed to 40 min of no-flow ischemia were reperfused with diltiazem (500 microM) or 3,4-dichlorobenzamil (300 microM) to block the Na+/Ca2+ exchanger and/or the L-type Ca2+ channel. High inhibitor concentrations were used to counter the binding of diltiazem and 3,4-dichlorobenzamil to albumin and red blood cells. Muscle Ca2+ accumulation, contractile function, and energy metabolism were assessed by measuring intracellular Ca2+ concentration ([Ca2+]i), Ca2+ influx, twitch tension, and high-energy phosphagens [ATP, total adenine nucleotides (TAN) and phosphocreatine (PCr)]. Compared with control reperfusion, diltiazem and 3,4-dichlorobenzamil reduced Ca2+ influx and attenuated the rise in [Ca2+]i in the fast-oxidative glycolytic plantaris (Pl) and the fast-glycolytic white gastrocnemius (WG). The inhibitor-induced decrease in Ca2+ influx was 1.5- to 2-fold greater with 3,4-dichlorobenzamil than with diltiazem. Coinciding with the reduced Ca2+ accumulation, diltiazem and 3,4-dichlorobenzamil enhanced the resynthesis of ATP (Pl and WG), PCr (Pl and WG), and TAN (Pl) compared with control reperfusion. 3,4-Dichlorobenzamil also augmented twitch-tension recovery. We conclude that Ca2+ accumulation during reperfusion 1) arises from L-type Ca2+ channel and Na+/Ca2+ exchange activation; and 2) impairs the metabolic and contractile recovery of skeletal muscle.

Hepatic preconditioning preserves energy metabolism during sustained ischemia

2000 ◽  
Vol 279 (1) ◽  
pp. G163-G171 ◽  
Author(s):  
C. Peralta ◽  
R. Bartrons ◽  
L. Riera ◽  
A. Manzano ◽  
C. Xaus ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Energy Charge ◽  
High Energy ◽  
Energetic Cost ◽  
Main Role ◽  
Adenylate Energy Charge ◽  
Glycogen Depletion ◽  
Adenine Nucleotide Pool

We evaluated the possibility that ischemic preconditioning could modify hepatic energy metabolism during ischemia. Accordingly, high-energy nucleotides and their degradation products, glycogen and glycolytic intermediates and regulatory metabolites, were compared between preconditioned and nonpreconditioned livers. Preconditioning preserved to a greater extent ATP, adenine nucleotide pool, and adenylate energy charge; the accumulation of adenine nucleosides and bases was much lower in preconditioned livers, thus reflecting slower adenine nucleotide degradation. These effects were associated with a decrease in glycogen depletion and reduced accumulation of hexose 6-phosphates and lactate. 6-Phosphofructo-2-kinase decreased in both groups, reducing the availability of fructose-2,6-bisphosphate. Preconditioning sustained metabolite concentration at higher levels although this was not correlated with an increased glycolytic rate, suggesting that adenine nucleotides and cAMP may play the main role in the modulation of glycolytic pathway. Preconditioning attenuated the rise in cAMP and limited the accumulation of hexose 6-phosphates and lactate, probably by reducing glycogen depletion. Our results suggest the induction of metabolic arrest and/or associated metabolic downregulation as energetic cost-saving mechanisms that could be induced by preconditioning.

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