ADENINE NUCLEOTIDE POOL MAINTENANCE DURING BACTERIAL GROWTH AND STARVATION

1979 ◽  
pp. 13-26
Author(s):  
Christopher J. Knowles
Keyword(s):  
Bacterial Growth ◽  
Adenine Nucleotide ◽  
Adenine Nucleotide Pool

Inhibition of xanthine oxidase ameliorates functional and metabolic impairment in type 2 diabetic hearts under pressure overload

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Igaki ◽  
A Osanami ◽  
M Tanno ◽  
T Sato ◽  
T Ogawa ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Xanthine Oxidase ◽  
Adenine Nucleotide ◽  
Vascular Dysfunction ◽  
Pressure Overload ◽  
Diabetic Control ◽  
Funding Source ◽  
National Budget ◽  
Adenine Nucleotide Pool

Abstract Background We recently reported that upregulated AMP deaminase (AMPD), via reduction in the tissue adenine nucleotide pool, contributes to exacerbation of diastolic dysfunction under pressure overload in OLETF, a rat model of obese type 2 diabetes (T2DM). Upregulated AMPD also possibly promotes xanthine oxidase (XO)-mediated ROS production, since AMPD deaminases AMP to IMP, which is further converted to inosine, providing substrates of XO, hypoxanthine and xanthine. Here, we examined the hypothesis that inhibition of XO ameliorates the pressure overload-induced diastolic dysfunction by suppression of ROS-mediated mitochondrial dysfunction and/or vascular dysfunction in T2DM rats. Methods and results Metabolomic analyses revealed that levels of xanthine and uric acid in the LV myocardium were significantly higher by 37% and 51%, respectively, in OLETF than in LETO, non-diabetic control rats, under the condition of phenylephrine-induced pressure overloading (200–230 mmHg). Myocardial XO activity in OLETF was 57.9% higher than that in LETO, which may be attributed to 31% higher level of inosine, a positive regulator of XO, in OLETF than in LETO. The activity of XO was significantly attenuated by administration of topiroxostat, an XO inhibitor at 0.5 mg/kg/day for 14 days. Pressure volume loop analyses showed that the pressure overloading resulted in significantly higher LVEDP in OLETF than in LETO (18.3±1.5 vs. 12.2±1.3 mmHg, p<0.05, n=7), though LVEDPs at baseline were comparable in OLETF and LETO (5.6±0.4 vs. 4.7±0.7 mmHg). Treatment with topiroxostat significantly suppressed the pressure overload-induced elevation of LVEDP in OLETF (18.3±1.5 vs. 11.3±1.1 mmHg, p<0.05) but not in LETO. Under the condition of pressure overloading, Ea/Ees, an index for ventricular-arterial coupling, was higher in OLETF than in LETO (2.3±0.3 vs. 1.6±0.3, p<0.05), and it was also improved by topiroxostat in OLETF (1.2±0.2, p<0.05). Myocardial ATP content was lower in OLETF than in LETO (2966±400 vs. 1818±171 nmol/g wet tissue, p<0.05), and treatment with topiroxostat significantly restored the ATP level (2629±307 nmol/g wet tissue). The LV myocardium of OLETF under pressure overload showed significantly higher level of malondialdehyde and 4-hydroxynonenal, an indicator of lipid peroxidation, than that of LETO. Measurement of oxygen consumption rate by Seahorse XFe96 Analyzer in mitochondria isolated from LV tissues revealed that state 3 respiration was significantly suppressed in OLETF by 43% compared to LETO, and it was restored by treatment with topiroxostat. Conclusion Both activity and substrates of XO are increased in T2DM hearts, in which upregulation of AMPD may play a role. Inhibition of XO ameliorates pressure overload-induced diastolic dysfunction and improves ventricular-arterial coupling in diabetic hearts, most likely through protection of mitochondrial function from ROS-mediated injury. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant-in-aid for Scientific Research (#26461132, #17K09584) from the Japanese Society for the Promotion of Science

scholarly journals The role of glutamine oxidation and the purine nucleotide cycle for adaptation of tumour energetics to the transition from the anaerobic to the aerobic state

1988 ◽  
Vol 252 (2) ◽  
pp. 381-386 ◽  
Author(s):  
Z Kovacević ◽  
D Jerance ◽  
O Brkljac
Keyword(s):  
Adenine Nucleotide ◽  
The Other ◽  
Purine Nucleotide ◽  
Purine Nucleotide Cycle ◽  
Adenine Nucleotide Pool

It is proposed that the purine nucleotide cycle and glutamine oxidation play a key role in the adaptation of tumour energetics to the transition from the anaerobic to the aerobic state. In support of this proposal, it was found that glutamine and inosine markedly increase total adenylates in the presence of oxygen, whereas the addition of hadacidin abolishes this effect. Transition of the cells from the anaerobic to the aerobic state, and vice versa, in the presence of glutamine plus inosine revealed that there are two components of the adenine nucleotide pool, one which is stable and the other which is variable and responds to the aerobic-anaerobic transition. This part of the pool undergoes degradation or resynthesis owing to activation of the enzymes of the purine nucleotide cycle. Resynthesis of the pool is accompanied by substantial net utilization of aspartate, which is produced by glutamine oxidation. This is supported by the experiments in which the cells were alternately incubated with nitrogen or oxygen, demonstrating that hadacidin significantly decreased utilization of aspartate and regeneration of ATP owing to inhibition of adenylosuccinate synthase.

Early effects of phenobarbital on the adenine nucleotide pool of rat liver

1972 ◽  
Vol 21 (14) ◽  
pp. 1929-1934 ◽  
Author(s):  
Roy McCauley ◽  
John O'Neill ◽  
Daniel Couri
Keyword(s):  
Rat Liver ◽  
Adenine Nucleotide ◽  
Early Effects ◽  
Adenine Nucleotide Pool

scholarly journals Nucleotide and Serotonin Metabolism in Platelets With Defective Secondary Aggregation

Blood ◽  
1974 ◽  
Vol 44 (6) ◽  
pp. 789-800 ◽  
Author(s):  
F. I. Pareti ◽  
H. J. Day ◽  
D. C. B. Mills
Keyword(s):  
Platelet Aggregation ◽  
Adenine Nucleotide ◽  
Platelet Rich Plasma ◽  
Adenine Nucleotides ◽  
Rapid Rate ◽  
Serotonin Metabolism ◽  
Release Reaction ◽  
Atp Breakdown ◽  
Platelet Defects ◽  
Adenine Nucleotide Pool

Abstract Ten patients with qualitative platelet defects have been investigated. All of the patients had impairment of secondary platelet aggregation induced by ADP, epinephrine, and collagen, and a defective release reaction. In seven patients from four families, the abnormality was consistent with the lack of a metabolically inert adenine nucleotide pool. Four of these patients, from two families, were albinos. Platelets from all of these patients had lower than normal amounts of adenine nucleotides and 5HT; the ability of these platelets to incorporate the amine was reduced and 5HT was metabolized at an abnormally rapid rate in platelet-rich plasma. It was not possible to distinguish the defect present in the albinos from that in the normally pigmented patients. Three other patients had normal amounts of platelet adenine nucleotides and 5HT; platelet aggregation and the release of adenine nucleotides induced by collagen were impaired. Metabolic ATP breakdown, during collagen aggregation, was also decreased. This defect is similar to that induced in normal platelets by aspirin. Studies on intracellular synthesis of cyclic 3'5' AMP in both groups of patients showed that the platelets were normally responsive to PGE1 and the antagonism of PGE1 by ADP and by epinephrine was also normal.

Purine metabolic pathways in rat hindlimb perfusion model during ischemia and reperfusion

1993 ◽  
Vol 265 (4) ◽  
pp. H1074-H1081 ◽  
Author(s):  
B. Soussi ◽  
K. Lagerwall ◽  
J. P. Idstrom ◽  
T. Schersten
Keyword(s):  
Skeletal Muscle ◽  
Blood Cell ◽  
Xanthine Oxidase ◽  
Flow Rate ◽  
Adenine Nucleotide ◽  
Vascular Endothelial Cell ◽  
Nucleotide Metabolism ◽  
Computer Simulation Model ◽  
Tissue Homogenates ◽  
Adenine Nucleotide Pool

The perfused rat hindlimb preparation was used with a blood cell-free perfusate to investigate alterations in the purine nucleotide metabolism, flow rate, perfusion pressure, and venous excretion in response to ischemia and ischemia followed by reperfusion in skeletal muscle. The development of a physical hindrance during postischemic reperfusion, indicated by an increase in reperfusion pressure and a decrease in flow rate, coincided with a 90% decrease in phosphocreatine and a 50-70% reduction in total adenine nucleotide pool. The reflow impairment could not be explained by blood cell plugging of the capillaries. Washout of several metabolites was demonstrated during reperfusion. Hypoxanthine accumulated intracellularly during ischemia, and a substantial amount of uric acid was excreted into the venous effluent during reperfusion. The experimental data were fitted into a computer simulation model of the purine pathways. The model indicated that AMP deaminase was the predominant enzymatic pathway for the AMP degradation. It was demonstrated that ATP preferably accumulated as inosine-5'-monophosphate during ischemia and that xanthine oxidase was undetectable in skeletal muscle tissue homogenates. However, vascular endothelial cell xanthine oxidase activity responsible for a free radical-induced reperfusion injury could not be excluded.

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.

Interstitial purine metabolites in hearts with LV remodeling

2004 ◽  
Vol 286 (2) ◽  
pp. H677-H684 ◽  
Author(s):  
Andrey V. Gourine ◽  
Qingsong Hu ◽  
Paul R. Sander ◽  
Aleksandr I. Kuzmin ◽  
Nadia Hanafy ◽  
...  
Keyword(s):  
Uric Acid ◽  
Sham Group ◽  
Adenine Nucleotide ◽  
Left Ventricular ◽  
Atp Depletion ◽  
Sham Operation ◽  
Adrenergic Stimulation ◽  
Purine Metabolites ◽  
Lv Remodeling ◽  
Adenine Nucleotide Pool

The myocardial ATP concentration is significantly decreased in failing hearts, which may be related to the progressive loss of the myocardial total adenine nucleotide pool. The total myocardial interstitial purine metabolites (IPM) in the dialysate of interstitial fluid could reflect the tissue ATP depletion. In rats, postmyocardial infarction (MI) left ventricular (LV) remodeling was induced by ligation of the coronary artery. Cardiac microdialysis was employed to assess changes of IPM in response to graded β-adrenergic stimulation with isoproterenol (Iso) in myocardium of hearts with post-MI LV remodeling (MI group) or hearts with sham operation (sham group). The dialysate samples were analyzed for adenosine, inosine, hypoxanthine, xanthine, and uric acid. LV volume was greater in the MI group (2.2 ± 0.2 ml/kg) compared with the sham group (1.3 ± 0.2 ml/kg, P < 0.05). Infarct size was 28 ± 4%. The baseline dialysate level of uric acid was higher in the MI group (18.9 ± 3.4 μmol) compared with the sham group (4.6 ± 0.7 μmol, P < 0.01). During and after Iso infusion, the dialysate levels of adenosine, xanthine, and uric acid were all significantly higher in the MI group. Thus the level of IPM is increased in hearts with postinfarction LV remodeling both at baseline and during Iso infusion. These results suggest that the decreased myocardial ATP level in hearts with post-MI LV remodeling may be caused by the chronic depletion of the total adenine nucleotide pool.

scholarly journals Mechanisms of adenosine 5'-monophosphate catabolism in human erythrocytes

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 988-992 ◽  
Author(s):  
DE Paglia ◽  
WN Valentine ◽  
M Nakatani ◽  
RA Brockway
Keyword(s):  
Potential Role ◽  
Adenine Nucleotide ◽  
Acidic Ph ◽  
Amp Deaminase ◽  
Severe Deficiency ◽  
Erythrocyte Enzyme ◽  
Senescent Erythrocytes ◽  
Adenine Nucleotide Pool ◽  
Normal Controls

Abstract Uncertainties regarding the role of pyrimidine nucleotidase (PyrNase) in AMP catabolism were resolved by studies of erythrocytes from normal controls, controls with young mean cell ages, and patients with hereditary hemolytic anemia due to severe deficiency of PyrNase. Hemolysates from the latter exhibited undiminished capacity to dephosphorylate AMP over a broad range of pH, indicating that PyrNase was not directly involved. In each subject group, the rates of AMP dephosphorylation between pH 5.1 and 8.3 were indistinguishable from those of IMP, suggesting a potential role for AMP-deaminase, an erythrocyte enzyme that was stimulated by coformycin at pH 7.2. Quantitative analysis of catabolites in incubated hemolysates confirmed that AMP degradation preferentially occurred via deamination to IMP with subsequent dephosphorylation by another erythrocyte nucleotidase isozyme, deoxyribonucleotidase. Both AMP-deaminase and deoxyribonucleotidase have acidic pH optima with minimal activities at physiologic pH, suggesting that this pathway of AMP catabolism could accelerate depletion of the adenine nucleotide pool and thereby mediate the demise of senescent erythrocytes sequestered in the spleen.

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