Uremic encephalopathy: role of brain energy metabolism

1984 ◽  
Vol 247 (3) ◽  
pp. F527-F532
Author(s):  
C. A. Mahoney ◽  
P. Sarnacki ◽  
A. I. Arieff
Keyword(s):  
Renal Failure ◽  
Redox State ◽  
Adenine Nucleotide ◽  
Energy Charge ◽  
High Energy ◽  
Normal Brain ◽  
High Energy Phosphates ◽  
Adenine Nucleotide Pool ◽  
The Brain ◽  
Brain Energy

Uremia is associated with decreased brain oxygen consumption in humans and with decreased brain energy consumption in rodent models of acute renal failure. We measured the levels of high-energy phosphates and glycolytic intermediates in the brain of dogs with acute or chronic renal failure. We used methods of rapid brain tissue fixation that trap these labile metabolites at their in vivo levels. Creatine phosphate, ATP, and glucose were normal in the brain of animals with renal failure, indicating a normal brain energy reserve. The brain energy charge, which is the fraction of the total adenine nucleotide pool that contains high-energy phosphates, (ATP + 1/2ADP)/(ATP + ADP + AMP), was also normal despite an 8% decrease in the total adenine nucleotide pool. Mild hypoxia failed to alter the level of any of these metabolites. The brain redox state, (NAD+)/(NADH), was normal to high in acute renal failure, suggesting that oxygen supply was not limiting oxygen consumption. In the face of normal brain energy reserves, energy charge, and redox state, the decreased energy consumption of uremic brain probably results from decreased demand rather than limited supply.

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.

Anaerobic energy provision in aged skeletal muscle during tetanic stimulation

1991 ◽  
Vol 70 (4) ◽  
pp. 1787-1795 ◽  
Author(s):  
C. B. Campbell ◽  
D. R. Marsh ◽  
L. L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Energy Demand ◽  
Energy Charge ◽  
High Energy ◽  
High Energy Phosphates ◽  
Fischer 344 ◽  
Charge Potential ◽  
Anaerobic Energy ◽  
Gastrocnemius Muscles

The effect of age on skeletal muscle anaerobic energy metabolism was investigated in adult (11 mo) and aged (25 mo) Fischer 344 rats. Hindlimb skeletal muscles innervated by the sciatic nerve were stimulated to contract with trains of supramaximal impulses (100 ms, 80 Hz) at a train rate of 1 Hz for 60 s, with an occluded circulation. Soleus, plantaris, and red and white gastrocnemius (WG) were sampled from control and stimulated limbs. All muscle masses were reduced with age (9-13%). Peak isometric tensions, normalized per gram of wet muscle, were lower throughout the stimulation in the aged animals (28%). The potential for anaerobic ATP provision was unaltered with age in all muscles, because resting high-energy phosphates and glycogen contents were similar to adult values. Anaerobic ATP provision during stimulation was unaltered by aging in soleus, plantaris, and red gastrocnemius muscles. In the WG, containing mainly fast glycolytic (FG) fibers, ATP and phosphocreatine contents were depleted less in aged muscle. In situ glycogenolysis and glycolysis were 90.0 +/- 4.8 and 69.3 +/- 2.6 mumol/g dry muscle (dm) in adult WG and reduced to 62.3 +/- 6.9 and 51.5 +/- 5.5 mumol/g dm, respectively, in aged WG. Consequently, total anaerobic ATP provision was lower in aged WG (224.5 +/- 20.9 mumol/g dm) vs. adult (292.6 +/- 7.6 mumol/g dm) WG muscle. In summary, the decreased tetanic tension production in aged animals was associated with a decreased anaerobic energy production in FG fibers. Reduced high-energy phosphate use and a greater energy charge potential after stimulation suggested that the energy demand was reduced in aged FG fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Labeling of the releasable adenine nucleotides of washed human platelets

Blood ◽  
1977 ◽  
Vol 49 (1) ◽  
pp. 89-99 ◽  
Author(s):  
HJ Reimers ◽  
MA Packham ◽  
JF Mustard
Keyword(s):  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Energy Charge ◽  
Human Platelets ◽  
Transport Processes ◽  
Adenylate Energy Charge ◽  
Prolonged Incubation ◽  
Atp Pool ◽  
Adenine Nucleotide Pool

Abstract In rabbit platelets, the metabolically active ATP pool equilibrates with the releasable ATP pool within 1 day. The studies showing this have now been extended to human platelets. Human platelets labeled with 14C-adenosine or 14C-adenine were incubated for up to 10 hr in vitro at 37 degrees C. After 10 hr, about 12% of the total platelet 14C-ATP and 14C-ADP had become releasable with thrombin (4.2 units/ml). Lysis of platelets did not occur, since less than 1% of the platelet-bound 51Cr from platelets labeled with this radioisotope appeared in the ambient fluid upon thrombin treatment. The 14C-ATP/14C-ADP ratio of the released adenine nucleotides (7.6) was similar to the 14C-ATP/14C-ADP ratio of the nonreleasable adenine nucleotides (7.1) 2 hr after the labeling with 14C-adenosine. However, upon prolonged incubation (10 hr) in vitro, the 14C-ATP/14C-ADP ratio of the releasable adenine nucleotides decreased to 2.7. The adenylate energy charge and the 14C- ATP/14C-ADP ratio of the metabolic adenine nucleotide pool did not change significantly during the time of observation. The 14C-ATP content of the platelets decreased by less than 1% hr of incubation at 37 degrees C. These observations are interpreted to mean that the 14C is transferred from the metabolically active, nonreleasable adenine nucleotide pool of human platelets into the releasable adenine nucleotide pool as ATP and is partially hydrolyzed there to yield ADP. The transfer of ATP across the storage organelle membrane of platelets may be similar to transport processes in the chromaffin cells of the adrenal medulla and may represent a general phenomenon in cells that possess storage organelles containing adenine nucleotides.

scholarly journals A comparison of voluntary and electrically induced contractions by interleaved 1H- and 31P-NMRS in humans

2003 ◽  
Vol 94 (3) ◽  
pp. 1012-1024 ◽  
Author(s):  
M. Vanderthommen ◽  
S. Duteil ◽  
C. Wary ◽  
J. S. Raynaud ◽  
A. Leroy-Willig ◽  
...  
Keyword(s):  
Energy Charge ◽  
High Energy ◽  
Isometric Contractions ◽  
High Energy Phosphates ◽  
Type Ii ◽  
Metabolic Pattern ◽  
Cell Recruitment ◽  
Temporal And Spatial ◽  
Voluntary Contractions ◽  
Type Ii Fibers

Skeletal muscle voluntary contractions (VC) and electrical stimulations (ES) were compared in eight healthy men. High-energy phosphates and myoglobin oxygenation were simultaneously monitored in the quadriceps by interleaved1H- and 31P-NMR spectroscopy. For the VC protocol, subjects performed five or six bouts of 5 min with a workload increment of 10% of maximal voluntary torque (MVT) at each step. The ES protocol consisted of a 13-min exercise with a load corresponding to 10% MVT. For both protocols, exercise consisted of 6-s isometric contractions and 6-s rest cycles. For an identical mechanical level (10% MVT), ES induced larger changes than VC in the Pi-to-phosphocreatine ratio [1.38 ± 1.14 (ES) vs. 0.13 ± 0.04 (VC)], pH [6.69 ± 0.11 (ES) vs. 7.04 ± 0.07 (VC)] and myoglobin desaturation [43 ± 15.9 (ES) vs. 6.1 ± 4.6% (VC)]. ES activated the muscle facing the NMR coil to a greater extent than did VCs when evaluated under identical technical conditions. This metabolic pattern can be interpreted in terms of specific temporal and spatial muscle cell recruitment. Furthermore, at identical levels of energy charge, the muscle was more acidotic and cytoplasm appeared more oxygenated during ES than during VC. These results are in accordance with a preferential recruitment of type II fibers and a relative muscle hyperperfusion during ES.

scholarly journals Redox state and lactate accumulation in human skeletal muscle during dynamic exercise

1987 ◽  
Vol 245 (2) ◽  
pp. 551-556 ◽  
Author(s):  
K Sahlin ◽  
A Katz ◽  
J Henriksson
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Redox State ◽  
Lactate Production ◽  
High Energy ◽  
High Energy Phosphates ◽  
Vo2 Max ◽  
Muscle Lactate ◽  
Lactate Accumulation ◽  
Pyruvate Ratio

The relationship between the redox state and lactate accumulation in contracting human skeletal muscle was investigated. Ten men performed bicycle exercise for 10 min at 40 and 75% of maximal oxygen uptake [VO2(max.)], and to fatigue (4.8 +/- 0.6 min; mean +/- S.E.M.) at 100% VO2(max.). Biopsies from the quadriceps femoris muscle were analysed for NADH, high-energy phosphates and glycolytic intermediates. Muscle NADH was 0.20 +/- 0.02 mmol/kg dry wt. of muscle at rest, and decreased to 0.12 +/- 0.01 (P less than 0.01) after exercise at 40% VO2(max.), but no change occurred in the [lactate]/[pyruvate] ratio. These data, together with previous results on isolated cyanide-poisoned soleus muscle, where NADH increased while [lactate]/[pyruvate] ratio was unchanged [Sahlin & Katz (1986) Biochem. J. 239, 245-248], suggest that the observed changes in muscle NADH occurred within the mitochondria. After exercise at 75 and 100% VO2(max.), muscle NADH increased above the value at rest to 0.27 +/- 0.03 (P less than 0.05) and 0.32 +/- 0.04 (P less than 0.001) mmol/kg respectively. Muscle lactate was unchanged after exercise at 40% VO2(max.), but increased substantially at the higher work loads. At 40% VO2(max.), phosphocreatine decreased by 11% compared with the values at rest, and decreased further at the higher work loads. The decrease in phosphocreatine reflects increased ADP and Pi. It is concluded that muscle NADH decreases during low-intensity exercise, but increases above the value at rest during high-intensity exercise. The increase in muscle NADH is consistent with the hypothesis that the accelerated lactate production during submaximal exercise is due to a limited availability of O2 in the contracting muscle. It is suggested that the increases in NADH, ADP and Pi are metabolic adaptations, which primarily serve to activate the aerobic ATP production, and that the increased anaerobic energy production (phosphocreatine breakdown and lactate formation) is a consequence of these changes.

Pyruvate-fortified cardioplegia suppresses oxidative stress and enhances phosphorylation potential of arrested myocardium

2005 ◽  
Vol 289 (3) ◽  
pp. H1123-H1130 ◽  
Author(s):  
E. Marty Knott ◽  
Myoung-Gwi Ryou ◽  
Jie Sun ◽  
Abraham Heymann ◽  
Arti B. Sharma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Redox State ◽  
Energy State ◽  
High Energy ◽  
High Energy Phosphates ◽  
Cardioplegic Arrest ◽  
Phosphorylation Potential ◽  
Lactate And Pyruvate ◽  
Postischemic Myocardium

Cardioplegic arrest for bypass surgery imposes global ischemia on the myocardium, which generates oxyradicals and depletes myocardial high-energy phosphates. The glycolytic metabolite pyruvate, but not its reduced congener lactate, increases phosphorylation potential and detoxifies oxyradicals in ischemic and postischemic myocardium. This study tested the hypothesis that pyruvate mitigates oxidative stress and preserves the energy state in cardioplegically arrested myocardium. In situ swine hearts were arrested for 60 min with a 4:1 mixture of blood and crystalloid cardioplegia solution containing 188 mM glucose alone (control) or with additional 23.8 mM lactate or 23.8 mM pyruvate and then reperfused for 3 min with cardioplegia-free blood. Glutathione (GSH), glutathione disulfide (GSSG), and energy metabolites [phosphocreatine (PCr), creatine (Cr), Pi] were measured in myocardium, which was snap frozen at 45 min arrest and 3 min reperfusion to determine antioxidant GSH redox state (GSH/GSSG) and PCr phosphorylation potential {[PCr]/([Cr][Pi])}. Coronary sinus 8-isoprostane indexed oxidative stress. Pyruvate cardioplegia lowered 8-isoprostane release ∼40% during arrest versus control and lactate cardioplegia. Lactate and pyruvate cardioplegia dampened ( P < 0.05 vs. control) the surge of 8-isoprostane release following reperfusion. Pyruvate doubled GSH/GSSG versus lactate cardioplegia during arrest, but GSH/GSSG fell in all three groups after reperfusion. Myocardial [PCr]/([Cr][Pi]) was maintained in all three groups during arrest. Pyruvate cardioplegia doubled [PCr]/([Cr][Pi]) versus control and lactate cardioplegia after reperfusion. Pyruvate cardioplegia mitigates oxidative stress during cardioplegic arrest and enhances myocardial energy state on reperfusion.

Hyperglycemia during Hypothermic Canine Cardiopulmonary Bypass Increases Cerebral Lactate 

1995 ◽  
Vol 82 (2) ◽  
pp. 512-520 ◽  
Author(s):  
Alan E. Feerick ◽  
William E. Johnston ◽  
Larry W. Jenkins ◽  
Cheng Y. Lin ◽  
Jonathan H. Mackay ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebrospinal Fluid ◽  
Cerebral Blood Flow ◽  
Cardiopulmonary Bypass ◽  
Energy Charge ◽  
Canine Model ◽  
High Energy ◽  
Serum Glucose ◽  
High Energy Phosphates ◽  
Lactate Levels

Background Hyperglycemia frequently occurs during cardiopulmonary bypass (CPB), although its direct effects on cerebral perfusion and metabolism are not known. Using a canine model of hypothermic CPB, we tested whether hyperglycemia alters cerebral blood flow and metabolism and cerebral energy charge. Methods Twenty anesthetized dogs were randomized into hyperglycemic (n = 10) and normoglycemic (n = 10) groups. The hyperglycemic group received an infusion of D50W, and the normoglycemic animals received an equal volume of 0.9% NaCl. Both groups underwent 120 min of hypothermic (28 degrees C) CPB using membrane oxygenators, followed by rewarming and termination of CPB. Cerebral blood flow (radioactive microspheres) and the cerebral metabolic rate for oxygen were measured intermittently during the experiment and brain tissue metabolites were obtained after bypass. Results Before CPB, the glucose-treated animals had higher serum glucose levels (534 +/- 12 mg/dL; mean +/- SE) than controls (103 +/- 4 mg/dL; P &lt; 0.05), and this difference was maintained throughout the study. Cerebral blood flow and metabolism did not differ between groups at any time during the experiment. Sagittal sinus pressure was comparable between groups throughout CPB. Tissue high-energy phosphates and water contents were similar after CPB, although cerebral lactate levels were greater in hyperglycemic (37.2 +/- 5.7 mumol/g) than normoglycemic animals (19.7 +/- 3.7 mumol/g; P &lt; 0.05). After CPB, pH values of cerebrospinal fluid for normoglycemic (7.33 +/- 0.01) and hyperglycemic (7.34 +/- 0.01) groups were similar. Conclusions Hyperglycemia during CPB significantly increases cerebral lactate levels without adversely affecting cerebral blood flow and metabolism, cerebrospinal fluid pH, or cerebral energy charge.

scholarly journals Hyperammonaemia does not impair brain function in the absence of net glutamine synthesis

1991 ◽  
Vol 277 (3) ◽  
pp. 697-703 ◽  
Author(s):  
R A Hawkins ◽  
J Jessy
Keyword(s):  
Amino Acids ◽  
Brain Function ◽  
Aromatic Amino Acids ◽  
Preceding Paper ◽  
Glucose Consumption ◽  
High Energy ◽  
High Energy Phosphates ◽  
Intermediary Metabolites ◽  
Glutamine Synthesis ◽  
The Brain

1. It has been established that chronic hyperammonaemia, whether caused by portacaval shunting or other means, leads to a variety of metabolic changes, including a depression in the cerebral metabolic rate of glucose (CMRGlc) increased permeability of the blood-brain barrier to neutral amino acids, and an increase in the brain content of aromatic amino acids. The preceding paper [Jessy, DeJoseph & Hawkins (1991) Biochem. J. 277, 693-696] showed that the depression in CMRGlc caused by hyperammonaemia correlated more closely with glutamine, a metabolite of ammonia, than with ammonia itself. This suggested that ammonia (NH3 and NH4+) was without effect. The present experiments address the question whether ammonia, in the absence of net glutamine synthesis, induces any of the metabolic symptoms of cerebral dysfunction associated with hyperammonaemia. 2. Small doses of methionine sulphoximine, an inhibitor of glutamine synthetase, were used to raise the plasma ammonia levels of normal rats without increasing the brain glutamine content. These hyperammonaemic rats, with plasma and brain ammonia levels equivalent to those known to depress brain function, behaved normally over 48 h. There was no depression of cerebral energy metabolism (i.e. the rate of glucose consumption). Contents of key intermediary metabolites and high-energy phosphates were normal. Neutral amino acid transport (tryptophan and leucine) and the brain contents of aromatic amino acids were unchanged. 3. The data suggest that ammonia is without effect at concentrations less than 1 mumol/ml if it is not converted into glutamine. The deleterious effect of chronic hyperammonaemia seems to begin with the synthesis of glutamine.

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.

Skeletal muscle energy metabolism during prolonged, fatiguing exercise

1999 ◽  
Vol 87 (6) ◽  
pp. 2341-2347 ◽  
Author(s):  
Mark A. Febbraio ◽  
Jane Dancey
Keyword(s):  
Prolonged Exercise ◽  
Adenine Nucleotide ◽  
Degradation Products ◽  
High Energy ◽  
Cycle Ergometer ◽  
Limiting Factor ◽  
Fatiguing Exercise ◽  
Muscle Energy Metabolism ◽  
Adenine Nucleotide Pool ◽  
Glycogen Stores

A depletion of phosphocreatine (PCr), fall in the total adenine nucleotide pool (TAN = ATP + ADP + AMP), and increase in TAN degradation products inosine 5′-monophosphate (IMP) and hypoxanthine are observed at fatigue during prolonged exercise at 70% maximal O2 uptake in untrained subjects [J. Baldwin, R. J. Snow, M. F. Carey, and M. A. Febbraio. Am. J. Physiol. 277 ( Regulatory Integrative Comp. Physiol.46): R295–R300, 1999]. The present study aimed to examine whether these metabolic changes are also prevalent when exercise is performed below the blood lactate threshold (LT). Six healthy, untrained humans exercised on a cycle ergometer to voluntary exhaustion at an intensity equivalent to 93 ± 3% of LT (∼65% peak O2 uptake). Muscle biopsy samples were obtained at rest, at 10 min of exercise, ∼40 min before fatigue (F−40 =143 ± 13 min), and at fatigue (F = 186 ± 31 min). Glycogen concentration progressively declined ( P < 0.01) to very low levels at fatigue (28 ± 6 mmol glucosyl U/kg dry wt). Despite this, PCr content was not different when F−40 was compared with F and was only reduced by 40% when F was compared with rest (52.8 ± 3.7 vs. 87.8 ± 2.0 mmol/kg dry wt; P < 0.01). In addition, TAN concentration was not reduced, IMP did not increase significantly throughout exercise, and hypoxanthine was not detected in any muscle samples. A significant correlation ( r = 0.95; P < 0.05) was observed between exercise time and glycogen use, indicating that glycogen availability is a limiting factor during prolonged exercise below LT. However, because TAN was not reduced, PCr was not depleted, and no correlation was observed between glycogen content and IMP when glycogen stores were compromised, fatigue may be related to processes other than those involved in muscle high-energy phosphagen metabolism.

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