scholarly journals Hypoxia and the energy charge of the cerebral adenylate pool

1972 ◽  
Vol 127 (2) ◽  
pp. 351-355 ◽  
Author(s):  
J. W. Ridge
Keyword(s):  
Rat Brain ◽  
Feedback Inhibition ◽  
Adenine Nucleotide ◽  
Energy Charge ◽  
Nucleotide Synthesis ◽  
Limited Ability ◽  
Adenylate Pool ◽  
The Brain

A brief period of anoxia in vivo causes a transitory decrease in the size of the adenylate pool in the rat brain. This is probably caused by feedback inhibition by AMP of adenine nucleotide synthesis. Exposing rats to various degrees of hypoxia suggests that the sensitivity of the brain to lack of O2 results from the brain's limited ability to maintain an adequate energy charge in unfavourable circumstances.

Metabolism of adenine nucleotides in the cultured fetal mouse heart

1977 ◽  
Vol 233 (2) ◽  
pp. H282-H288
Author(s):  
I. A. Kaufman ◽  
N. F. Hall ◽  
M. A. DeLuca ◽  
J. S. Ingwall ◽  
S. E. Mayer
Keyword(s):  
Organ Culture ◽  
Adenosine Deaminase ◽  
De Novo ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Energy Charge ◽  
Mouse Heart ◽  
Nucleotide Synthesis ◽  
Fetal Mouse ◽  
Deprivation Period

Intact beating fetal mouse hearts in organ culture were deprived of oxygen and glucose for up to 4 h, resulting in loss of beating, an 80% fall in ATP, reduction of energy charge from 0.85 to 0.48, and doubling of total nucleoside concentration. Radiolabeled adenine nucleotides were degraded to hypoxanthine and inosine, which were lost from the hearts into the medium during the deprivation period. Adenosine and adenine also appeared in the medium when adenosine deaminase was inhibited. After 24 h of O2 and glucose resupply, ATP returned to 60% of control, and energy charge rose to 0.76. Labeled nucleosides and bases remaining in the heart or exogenous labeled adenine were utilized to resynthesize ATP. [14C]glycine was rapidly taken up by recovering hearts but was not used for de novo adenine nucleotide synthesis. Ability to recover ATP and spontaneous contraction appear related to residual nucleotide and nucleoside content rather than to energy charge.

In vivo correlation between liver and blood energy status as evidenced by chronic treatment of carbon tetrachloride and adenosine to rats

1994 ◽  
Vol 72 (10) ◽  
pp. 1252-1256 ◽  
Author(s):  
Rolando Hernández-Muñoz ◽  
Victoria Chagoya de Sánchez
Keyword(s):  
Carbon Tetrachloride ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Adenine Nucleotide ◽  
Energy Availability ◽  
Energy Status ◽  
Nucleotide Synthesis ◽  
Purine Ring ◽  
Progressive Liver Damage

Several tissues, such as red blood cells, depend on the liver supply of the purine ring for adenine nucleotide synthesis. We explored whether progressive liver damage, induced by carbon tetrachloride (CCl4), is accompanied by alterations in liver and blood energy status. After 4 weeks of CCl4 treatment, liver ATP, ATP/ADP, and energy status were decreased. Blood ATP remained normal, whereas the blood energy status was also diminished. After 8 weeks the changes were more evident, and a significant decrease of total liver nucleotides was also found. In the blood, the changes paralleled those in the liver. Simultaneous administration of adenosine counteracted the CCl4 effects. A good correlation (r = 0.79, p < 0.01) between the liver and blood ATP changes and a very significant relationship between liver and blood ATP/ADP ratio (r = 0.92, p < 0.001) were observed. Therefore, the data suggest that liver function could influence the energy availability in other tissues, such as red blood cells, perhaps as a result of its capacity to provide purine rings for extrahepatic synthesis of adenine nucleotides.Key words: liver–blood ATP interrelationship, cirrhotic rats, carbon tetrachloride, energy parameters, adenosine.

scholarly journals Conversion of ethanolamine, monomethylethanolamine and dimethylethanolamine to choline-containing compounds by neurons in culture and by the rat brain

1989 ◽  
Vol 264 (2) ◽  
pp. 555-562 ◽  
Author(s):  
C Andriamampandry ◽  
L Freysz ◽  
J N Kanfer ◽  
H Dreyfus ◽  
R Massarelli
Keyword(s):  
Rat Brain ◽  
Primary Culture ◽  
De Novo ◽  
Water Soluble ◽  
Intraventricular Injection ◽  
Chick Embryos ◽  
Fetal Rat ◽  
Derivatives Of ◽  
The Brain

The incubation of neurons from chick embryos in primary culture with [3H]ethanolamine revealed the conversion of this base into monomethyl, dimethyl and choline derivatives, including the corresponding free bases. Labelling with [methyl-3H]monomethylethanolamine and [methyl-3H]dimethylethanolamine supported the conclusion that in chick neuron cultures, phosphoethanolamine appears to be the preferential substrate for methylation, rather than ethanolamine or phosphatidylethanolamine. The methylation of the latter two compounds, in particular that of phosphatidylethanolamine, was seemingly stopped at the level of their monomethyl derivatives. Fetal rat neurons in primary culture incubated with [3H]ethanolamine showed similar results to those observed with chick neurones. However, phosphoethanolamine and phosphatidylethanolamine and, to a lesser extent, free ethanolamine, appeared to be possible substrates for methylation reactions. The methylation of water-soluble ethanolamine compounds de novo was further confirmed by experiments performed in vivo by intraventricular injection of [3H]ethanolamine. Phosphocholine and the monomethyl and dimethyl derivatives of ethanolamine were detected in the brain 15 min after injection.

scholarly journals Adenine nucleotide levels in Rhodospirillum rubrum during switch-off of whole-cell nitrogenase activity

1984 ◽  
Vol 224 (3) ◽  
pp. 961-969 ◽  
Author(s):  
T D Paul ◽  
P W Ludden
Keyword(s):  
Protein Modification ◽  
Rhodospirillum Rubrum ◽  
Adenine Nucleotide ◽  
Nitrogenase Activity ◽  
Energy Charge ◽  
Whole Cell ◽  
Fe Protein ◽  
Nucleotide Pools ◽  
Phenazine Methosulphate

Adenine nucleotide pools were measured in Rhodospirillum rubrum cultures that contained nitrogenase. The average energy charge [([ATP] + 1/2[ADP])/([ATP] + [ADP] + [AMP])] was found to be 0.66 and 0.62 in glutamate-grown and N-limited cultures respectively. Treatment of glutamate-grown cells with darkness, ammonia, glutamine, carbonyl cyanide m-chlorophenylhydrazone, or phenazine methosulphate resulted in perturbations in the adenine nucleotide pools, and led to loss of whole-cell nitrogenase activity and modification in vivo of the Fe protein. Treatment of N-limited cells resulted in similar changes in adenine nucleotide pools but not enzyme modification. No correlations were found between changes in adenine nucleotide pools or ratios of these pools and switch-off of nitrogenase activity by Fe protein modification in vivo. Phenazine methosulphate inhibited whole-cell activity at low concentrations. The effect on nitrogenase activity was apparently independent of Fe protein modification.

scholarly journals The Retention Mechanism of Technetium-99m-HM-PAO: Intracellular Reaction with Glutathione

1988 ◽  
Vol 8 (1_suppl) ◽  
pp. S4-S12 ◽  
Author(s):  
Rudi D. Neirinckx ◽  
James F. Burke ◽  
Roger C. Harrison ◽  
Alan M. Forster ◽  
Allan R. Andersen ◽  
...  
Keyword(s):  
Steady State ◽  
Tissue Distribution ◽  
Rat Brain ◽  
Rate Constant ◽  
Conversion Rate ◽  
Brain Homogenate ◽  
Retention Mechanism ◽  
Technetium 99M ◽  
The Brain

Preparations of d,l- and meso-hexamethylpropyleneamine oxime (HM-PAO) labeled with technetium-99m were added to rat brain homogenates diluted with phosphate buffer (l: 10). The conversion of d,l-HM-PAO to hydrophilic forms took place with an initial rate constant of 0.12 min−1. Incubation of the brain homogenate with 2% diethyl maleate for 5 h decreased the homogenate's measured glutathione (GSH) concentration from 160 to 16 μ M and decreased the conversion rate to 0.012 min−1. Buffered aqueous solutions of glutathione rapidly converted the HM-PAO tracers to hydrophilic forms having the same chromatographic characteristics as found in the brain homogenates. The rate constant for the conversion reaction of d,l-HM-PAO in GSH aqueous solution was 208 and 317 L/mol/min in two different assay systems and for meso-HM-PAO the values were 14.7 and 23.2 L/mol/min, respectively. Rat brain has a GSH concentration of about 2.3 m M and the conversion of the d,l-HM-PAO due to GSH alone should proceed with a rate constant of 0.48 to 0.73 min−1 and be correspondingly 14-fold slower for meso-HM-PAO. In human brain, the in vivo data of Lassen et al. show a conversion rate constant of 0.80 min−1. This correspondence of values supports the notion that GSH may be important for the in vivo conversion of 99mTc-labeled HM-PAO to hydrophilic forms and may be the mechanism of trapping in brain and other cells. A kinetic model for the trapping of d,l- and meso-HM-PAO in tissue is developed that is based on data of GSH concentration in various organs. This model predicts that the d,l form rapidly reaches a steady state in tissue and the tissue distribution reflects a pattern dominated by blood flow. For the meso form, the model predicts that steady state is reached more slowly and the tissue distribution reflects a pattern dominated by glutathione concentration.

scholarly journals Regional distribution of SGLT activity in rat brain in vivo

2013 ◽  
Vol 304 (3) ◽  
pp. C240-C247 ◽  
Author(s):  
Amy S. Yu ◽  
Bruce A. Hirayama ◽  
Gerald Timbol ◽  
Jie Liu ◽  
Ana Diez-Sampedro ◽  
...  
Keyword(s):  
Rat Brain ◽  
Ex Vivo ◽  
Osmotic Shock ◽  
Regional Distribution ◽  
The Body ◽  
Specific Substrate ◽  
Ex Vivo Autoradiography ◽  
Molecular Imaging Probe ◽  
The Brain

Na+-glucose cotransporter (SGLT) mRNAs have been detected in many organs of the body, but, apart from kidney and intestine, transporter expression, localization, and functional activity, as well as physiological significance, remain elusive. Using a SGLT-specific molecular imaging probe, α-methyl-4-deoxy-4-[18F]fluoro-d-glucopyranoside (Me-4-FDG) with ex vivo autoradiography and immunohistochemistry, we mapped in vivo the regional distribution of functional SGLTs in rat brain. Since Me-4-FDG is not a substrate for GLUT1 at the blood-brain barrier (BBB), in vivo delivery of the probe into the brain was achieved after opening of the BBB by an established procedure, osmotic shock. Ex vivo autoradiography showed that Me-4-FDG accumulated in regions of the cerebellum, hippocampus, frontal cortex, caudate nucleus, putamen, amygdala, parietal cortex, and paraventricular nucleus of the hypothalamus. Little or no Me-4-FDG accumulated in the brain stem. The regional accumulation of Me-4-FDG overlapped the distribution of SGLT1 protein detected by immunohistochemistry. In summary, after the BBB is opened, the specific substrate for SGLTs, Me-4-FDG, enters the brain and accumulates in selected regions shown to express SGLT1 protein. This localization and the sensitivity of these neurons to anoxia prompt the speculation that SGLTs may play an essential role in glucose utilization under stress such as ischemia. The expression of SGLTs in the brain raises questions about the potential effects of SGLT inhibitors under development for the treatment of diabetes.

Changes in the adenylate energy charge ofNematospiroides dubiusandTrichostrongylus colubriformisparalysed by levamisolein vivo

Parasitology ◽  
1980 ◽  
Vol 81 (3) ◽  
pp. 593-601 ◽  
Author(s):  
M. J. Sharpe
Keyword(s):  
Oxygen Tension ◽  
Adenine Nucleotide ◽  
Energy Charge ◽  
Adenylate Energy Charge ◽  
Laboratory Mice ◽  
Trichostrongylus Colubriformis ◽  
Nucleotide Content ◽  
Nematospiroides Dubius ◽  
Low Levels

SUMMARYThe adenine nucleotide content and adenylate energy charge ofNematospiroides dubiusfrom laboratory mice and ofTrichostrongylus colubriformisfrom lambs has been measured. Administration of the anthelmintic, levamisole, to infected hosts resulted in only a slight fall in the adenylate energy charge ofN. dubiusover a 3-h period but there was a greater fall in the adenylate energy charge ofT. colubriformisduring this period. In neither case did the energy charge fall quickly, nor did it fall to the low levels which would be expected if the levamisole were inhibiting synthesis of ATP. The changes in energy charge of the nematodes which occurred following administration of levamisole to their hosts was of the order which can be satisfactorily explained by changes in the environment of the nematodes, such as reduced oxygen tension. It is concluded that the maintenance of levamisole-induced paralysis of these two species of trichostrongylein vivodoes not rely on the inhibition of fumarate reductase.

scholarly journals Elevation of the adenylate pool in rat cardiomyocytes by S-adenosyl-L-methionine.

2000 ◽  
Vol 47 (4) ◽  
pp. 1171-1178 ◽  
Author(s):  
R T Smolenski
Keyword(s):  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Normal Function ◽  
Cell Protein ◽  
Nucleotide Synthesis ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Adenylate Pool ◽  
Collagenase Perfusion ◽  
Subsequent Incorporation

Rapid resynthesis of the adenylate pool in cardiac myocytes is important for recovery of contractility and normal function of regulatory mechanisms in the heart. Adenosine and adenine are thought to be the most effective substrates for nucleotide synthesis, but the possibility of using other compounds has been studied very little in cardiomyocytes. In the present study, the effect of S-adenosyl-L-methionine (SAM) on the adenylate pool of isolated cardiomyocytes was investigated and compared to the effect of adenine and adenosine. Adult rat cardiomyocytes were isolated using the collagenase perfusion technique. The cells were incubated in the presence of adenine derivatives for 90 min followed by nucleotide determination by HPLC. The concentrations of adenine nucleotides expressed in nmol/mg of cell protein were initially 22.1 +/- 1.4, 4.0 +/- 0.3 and 0.70 +/- 0.08 for ATP, ADP and AMP, respectively (n = 10, +/- S.E.M.), and the total adenylate pool was 26.8 +/- 1.6. In the presence of 1.25 mM SAM in the medium, the adenylate pool increased by 5.2 +/- 0.4 nmol/mg of cell protein, but only if 1 mM ribose was additionally present in the medium. No changes were observed with SAM alone. A similar increase (by 4.9 +/- 0.6 nmol/mg protein) was observed after incubation with 1.25 mM adenine plus 1 mM ribose, but no increase was observed if ribose was omitted. Adenosine at 0.1 or 1.25 mM concentrations also caused an increase in the adenylate pool (by 5.2 +/- 1.0 and 5.2 +/- 0.9 nmol/mg protein, respectively), which in contrast to the SAM or adenine was independent of the additional presence of ribose. Thus, S-adenosyl-L-methionine could be used as a precursor of the adenylate pool in cardiomyocytes, which is as efficient in increasing the adenylate pool after 90 min of incubation as adenosine or adenine. Nucleotide synthesis from SAM involves the formation of adenine as an intermediate with its subsequent incorporation by adenine phosphoribosyltransferase.

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.

Hepatotrophic effects of insulin on glucose, glycogen, and adenine nucleotides in hepatocytes isolated from fed adult rats

1980 ◽  
Vol 58 (10) ◽  
pp. 1004-1011 ◽  
Author(s):  
Khursheed N. Jeejeebhoy ◽  
Joseph Ho ◽  
Rajni Mehra ◽  
Alan Bruce-Robertson
Keyword(s):  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Energy Charge ◽  
Close Correlation ◽  
Adult Rats ◽  
Fed State ◽  
Adenine Nucleotide Pool ◽  
Intracellular Glucose

In vivo observations have suggested that there is an hepatotrophic effect of insulin. By contrast, subsequent in vitro work, using the isolated perfused liver system, showed no effect or indeterminate effects of insulin on the transport of glucose into the hepatocyte. However because this system may not have endured long enough to show such an influence we explored the transport of glucose using a 48-h suspension culture of hepatocytes isolated from young adult fed rats, the suspension being infused continuously with insulin at a rate approximating the maximum entering portal blood in the fed state. (In a separate study phloridzin was added after 2 h of incubation.) DNA, intracellular glucose and its inward transport, glycogen, and the adenine nucleotides were measured at intervals. By comparison with control or untreated cells, insulin-treated cells showed significantly more DNA and intracellular glucose, and the differences were abolished by phloridzin. Glucose transport rates fell to low values in untreated controls and still lower with insulin plus phloridzin. but the initial rate was maintained to the end (48 h) by insulin alone. Results for glycogen were similar to those for intracellular glucose. There was a close correlation (r = 0.96) between these two. The total adenine nucleotide pool and the concentration of ATP were maintained for about 24 h and fell to half their initial values by 48 h. Insulin had increased these concentrations significantly by 6 h. Although concentrations of ADP and AMP decreased gradually in all groups of cells, insulin enhanced the level of ADP by 12 h but had no measurable effect on that of AMP. The energy charge increased slightly throughout incubation but more so (by 6 h) in the presence of insulin. In conclusion the data support the concept that in the longer term (> 12 h) insulin in the portal circulation maintains the characteristic free permeability of the hepatocyte to glucose and this permits a variety of effects related to glucose entry into the hepatocyte.

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