Control of adenine nucleotide metabolism in hepatic mitochondria from rats with ethanol-induced fatty liver

Male rats developed fatty liver after being fed on an ethanol-containing diet for 31 days. Liver mitochondria from these animals catalysed ATP synthesis at a slower rate when compared with mitochondria from pair-fed control rats (control mitochondria), and demonstrated lowered respiratory control with succinate as substrate, owing to a decrease in the State-3 respiratory rate. Respiration in the presence of uncoupler was comparable in mitochondria from both groups of rats. Translocation of both ATP and ADP was decreased in mitochondria from ethanol-fed rats, with ADP uptake being lowered more dramatically by ethanol feeding. Parameters influencing adenine nucleotide translocation were investigated in mitochondria from ethanol-fed rats. Experiments performed suggested that lowered adenine nucleotide translocation in these mitochondria is not the result of inhibition of the translocase by either long-chain acyl-CoA derivatives or unesterified fatty acids. Analysis of endogenous adenine nucleotides in these mitochondria revealed lowered ATP concentrations, but no decrease in total adenine nucleotides. In experiments where the endogenous ATP in these mitochondria was shifted to higher concentrations by incubation with oxidizable substrates or defatted bovine serum albumin, the rate of ADP translocation was increased, with a linear correlation being observed between endogenous ATP concentrations and the rate of ADP translocation. The depressed ATP concentration in mitochondria from ethanol-fed rats suggests that the ATP synthetase complex is replenishing endogenous ATP at a slower rate. The lowered ATPase activity of the ATP synthetase observed in submitochondrial particles from ethanol-fed animals suggests a decrease in the function of the synthetase complex. A decrease in the rate of ATP synthesis in mitochondria from ethanol-fed rats is sufficient to explain the decreased ADP translocation and State-3 respiration.

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The Platelet of the Newborn Infant – Adenine Nucleotide Metabolism and Release

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650026 ◽

1980 ◽

Vol 43 (02) ◽

pp. 099-103 ◽

Cited By ~ 9

Author(s):

J M Whaun ◽

P Lievaart ◽

Keyword(s):

Newborn Infant ◽

Adenine Nucleotide ◽

Platelet Rich Plasma ◽

Adenine Nucleotides ◽

Newborn Infants ◽

Specific Radioactivity ◽

Nucleotide Metabolism ◽

Breakdown Product ◽

Term Infants ◽

Adenine Nucleotide Metabolism

SummaryBlood from normal full term infants, mothers and normal adults was collected in citrate. Citrated platelet-rich plasma was prelabelled with 3H-adenine and reacted with release inducers, collagen and adrenaline. Adenine nucleotide metabolism, total adenine nucleotide levels and changes in sizes of these pools were determined in platelets from these three groups of subjects.At rest, the platelet of the newborn infant, compared to that of the mother and normal adult, possessed similar amounts of adenosine triphosphate (ATP), 4.6 ± 0.2 (SD), 5.0 ± 1.1, 4.9 ± 0.6 µmoles ATP/1011 platelets respectively, and adenosine diphosphate (ADP), 2.4 ± 0.7, 2.8 ± 0.6, 3.0 ± 0.3 umoles ADP/1011 platelets respectively. However the marked elevation of specific radioactivity of ADP and ATP in these resting platelets indicated the platelet of the neonate has decreased adenine nucleotide stores.In addition to these decreased stores of adenine nucleotides, infant platelets showed significantly impaired release of ADP and ATP on exposure to collagen. The release of ADP in infants, mothers, and other adults was 0.9 ± 0.5 (SD), 1.5 ± 0.5, 1.5 ± 0.1 umoles/1011 platelets respectively; that of ATP was 0.6 ± 0.3, 1.0 ± 0.1,1.3 ± 0.2 µmoles/1011 platelets respectively. With collagen-induced release, platelets of newborn infants compared to those of other subjects showed only slight increased specific radioactivities of adenine nucleotides over basal levels. The content of metabolic hypoxanthine, a breakdown product of adenine nucleotides, increased in both platelets and plasma in all subjects studied.In contrast, with adrenaline as release inducer, the platelets of the newborn infant showed no adenine nucleotide release, no change in total ATP and level of radioactive hypoxanthine, and minimal change in total ADP. The reason for this decreased adrenaline reactivity of infant platelets compared to reactivity of adult platelets is unknown.Infant platelets may have different membranes, with resulting differences in regulation of cellular processes, or alternatively, may be refractory to catecholamines because of elevated levels of circulating catecholamines in the newborn period.

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L-Arginine Intake Effect on Adenine Nucleotide Metabolism in Rat Parenchymal and Reproductive Tissues

The Scientific World JOURNAL ◽

10.1100/2012/208239 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4 ◽

Cited By ~ 5

Author(s):

G. Kocic ◽

J. Nikolic ◽

T. Jevtovic-Stoimenov ◽

D. Sokolovic ◽

H. Kocic ◽

...

Keyword(s):

Adenosine Deaminase ◽

Adenine Nucleotide ◽

Adenine Nucleotides ◽

Tissue Growth ◽

Nucleotide Metabolism ◽

Amp Deaminase ◽

Male Impotence ◽

Adenine Nucleotide Metabolism ◽

Adenosine Concentration ◽

Male Wistar Rats

L-arginine is conditionally essetcial amino acid, required for normal cell growth, protein synthesis, ammonia detoxification, tissue growth and general performance, proposed in the treatment of men sterility and prevention of male impotence. The aim of the present paper was to estimate the activity of the enzymes of adenine nucleotide metabolism:5′-nucleotidase (5′-NU), adenosine deaminase (ADA), AMP deaminase, and xanthine oxidase (XO), during dietary intake of L-arginine for a period of four weeks of male Wistar rats. Adenosine concentration in tissues is maintained by the relative activities of the adenosine-producing enzyme,5′-NU and the adenosine-degrading enzyme-ADA adenosine deaminase. Dietary L-arginine intake directed adenine nucleotide metabolism in liver, kidney, and testis tissue toward the activation of adenosine production, by increased5′-NU activity and decreased ADA activity. Stimulation of adenosine accumulation could be of importance in mediating arginine antiatherosclerotic, vasoactive, immunomodulatory, and antioxidant effects. Assuming that the XO activity reflects the rate of purine catabolism in the cell, while the activity of AMP deaminase is of importance in ATP regeneration, reduced activity of XO, together with the increased AMP-deaminase activity, may suggest that adenine nucleotides are presumably directed to the ATP regenerating process during dietary L-arginine intake.

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Effect of chronic ethanol administration on energy metabolism and phospholipase A2 activity in rat liver

Biochemical Journal ◽

10.1042/bj1780023 ◽

1979 ◽

Vol 178 (1) ◽

pp. 23-33 ◽

Cited By ~ 52

Author(s):

P I Spach ◽

J W Parce ◽

C C Cunningham

Keyword(s):

Fatty Acid ◽

Phospholipase A2 ◽

Phospholipid Fatty Acid ◽

Respiratory Control ◽

Liver Mitochondria ◽

Liquid Diet ◽

Male Rats ◽

Ethanol Administration ◽

Phospholipid Fatty Acid Composition ◽

Apparent Lack

1. For a period of 31 days male rats were given a liquid diet containing 36% of its energy as ethanol. Liver mitochondria from these animals demonstrated lowered respiratory control with succinate as substrate, a diminished energy-linked anilinonaphthalene-sulphonic acid fluorescence response, and lowered endogenous ATP concentrations. The phospholipid/protein ratio in mitochondria from these animals was unchanged; only minor alterations in the phospholipid fatty acid composition were observed. 2. In experiments where mitochondria were incubated at 18 degrees C in iso-osmotic sucrose (aging experiments), the above energy-linked properties were lost at an earlier time in organelles from ethanol-fed animals. Phospholipase A2 acitivty was depressed in mitochondria from control animals until respiratory control was lost and ATP was depleted. In contrast, no lag in the expression of phospholipase activity was observed in mitochondria from ethanol-fed rats. This loss of control of the phospholipase resulted in an earlier degradation of membrane phospholipids under the conditions of the aging experiments. 3. The ATPase (adenosine triphosphatase) activities, measured in freshly prepared tightly coupled mitochondria and in organelles uncoupled with carbonyl cyanide p-trifluoromethoxyphenylhydrazone, were not significantly different in ethanol-fed and liquid-diet control animals. When the mitochondria were aged at 18 degrees C, the activity increased with time of incubation in organelles from both groups of animals. A lag was observed, however, as the ATPase activity increased in control preparations. This lag was not present as APTase activity increased in mitochondria from ethanol-fed animals. 4. The significantly lowered values observed for energy-linked functions with succinate as an energy source demonstrate that ethanol elicits an alteration in liver mitochondria that affects the site II-site III regions of the oxidative-phosphorylation system. The apparent lack of control of the phospholipase A2 and ATPase activities in mitochondria from ethanol-fed animals suggests that the membrane microenvironment of these enzymes has been altered such that they can exert their catabolic effects more readily under conditions of mild perturbation. The fatty acid analyses demonstrate that the observed alterations both in the energy-linked functions and in control of the phospholipase and ATPase are not mediated through changes in the acyl chain composition of bulk-phase phospholipids.

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The effect of butacaine on adenine nucleotide binding and translocation in rat liver mitochondria

Biochemical Journal ◽

10.1042/bj1480527 ◽

1975 ◽

Vol 148 (3) ◽

pp. 527-531 ◽

Cited By ~ 10

Author(s):

D R Fayle ◽

G J Barritt ◽

F L Bygrave

Keyword(s):

Rat Liver ◽

Local Anaesthetic ◽

Binding Sites ◽

Adenine Nucleotide ◽

Adenine Nucleotides ◽

Nucleotide Binding ◽

Local Anaesthetics ◽

Liver Mitochondria ◽

Rat Liver Mitochondria ◽

Mitochondrial Inner Membrane

The effect of the local anaesthetic, butacaine, on adenine nucleotide binding and translocation in rat liver mitochondria partially depleted of their adenine nucleotide content was investigated. The range of butacaine concentrations that inhibit adenine nucleotide translocation and the extent of the inhibition are similar to the values obtained for native mitochondria. Butacaine does not alter either the total number of atractyloside-sensitive binding sites of depleted mitochondria, or the affinity of these sites for ADP or ATP under conditions where a partial inhibition of the rate of adenine nucleotide translocation is observed. The data are consistent with an effect of butacaine on the process by which adenine nucleotides are transported across the mitochondrial inner membrane rather than on the binding of adenine nucleotides to sites on the adenine nucleotide carrier. The results are briefly discussed in relation to the use of local anaesthetics in investigations of the mechanism of adenine nucleotide translocation.

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Invited Review: Contractile activity-induced mitochondrial biogenesis in skeletal muscle

Journal of Applied Physiology ◽

10.1152/jappl.2001.90.3.1137 ◽

2001 ◽

Vol 90 (3) ◽

pp. 1137-1157 ◽

Cited By ~ 464

Author(s):

David A. Hood

Keyword(s):

Transcription Factors ◽

Respiratory Chain ◽

Mitochondrial Biogenesis ◽

Adenine Nucleotide ◽

Contractile Activity ◽

Recovery Period ◽

Atp Synthesis ◽

Nucleotide Metabolism ◽

Significant Shift ◽

Mrna Levels

Chronic contractile activity produces mitochondrial biogenesis in muscle. This adaptation results in a significant shift in adenine nucleotide metabolism, with attendant improvements in fatigue resistance. The vast majority of mitochondrial proteins are derived from the nuclear genome, necessitating the transcription of genes, the translation of mRNA into protein, the targeting of the protein to a mitochondrial compartment via the import machinery, and the assembly of multisubunit enzyme complexes in the respiratory chain or matrix. Putative signals involved in initiating this pathway of gene expression in response to contractile activity likely arise from combinations of accelerations in ATP turnover or imbalances between mitochondrial ATP synthesis and cellular ATP demand, and Ca2+ fluxes. These rapid events are followed by the activation of exercise-responsive kinases, which phosphorylate proteins such as transcription factors, which subsequently bind to upstream regulatory regions in DNA, to alter transcription rates. Contractile activity increases the mRNA levels of nuclear-encoded proteins such as cytochrome c and mitochondrial transcription factor A (Tfam) and mRNA levels of upstream transcription factors like c- junand nuclear respiratory factor-1 (NRF-1). mRNA level changes are often most evident during the postexercise recovery period, and they can occur as a result of contractile activity-induced increases in transcription or mRNA stability. Tfam is imported into mitochondria and controls the expression of mitochondrial DNA (mtDNA). mtDNA contributes only 13 protein products to the respiratory chain, but they are vital for electron transport and ATP synthesis. Contractile activity increases Tfam expression and accelerates its import into mitochondria, resulting in increased mtDNA transcription and replication. The result of this coordinated expression of the nuclear and the mitochondrial genomes, along with poorly understood changes in phospholipid synthesis, is an expansion of the muscle mitochondrial reticulum. Further understanding of 1) regulation of mtDNA expression, 2) upstream activators of NRF-1 and other transcription factors, 3) the identity of mRNA stabilizing proteins, and 4) potential of contractile activity-induced changes in apoptotic signals are warranted.

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Stable enhancement of calcium retention in mitochondria isolated from rat liver after the administration of glucagon to the intact animal

Biochemical Journal ◽

10.1042/bj1760705 ◽

1978 ◽

Vol 176 (3) ◽

pp. 705-714 ◽

Cited By ~ 62

Author(s):

Veronica Prpić ◽

Terry L. Spencer ◽

Fyfe L. Bygrave

Keyword(s):

Rat Liver ◽

Molecular Mechanisms ◽

Adenine Nucleotide ◽

Adenine Nucleotides ◽

Mitochondrial Protein ◽

Liver Mitochondria ◽

Rat Liver Mitochondria ◽

Matrix Space ◽

The Matrix

1. Mitochondria isolated from rat liver by centrifugation of the homogenate in buffered iso-osmotic sucrose at between 4000 and 8000g-min, 1h after the administration in vivo of 30μg of glucagon/100g body wt., retain Ca2+ for over 45min after its addition at 100nmol/mg of mitochondrial protein in the presence of 2mm-Pi. In similar experiments, but after the administration of saline (0.9% NaCl) in place of glucagon, Ca2+ is retained for 6–8min. The ability of glucagon to enhance Ca2+ retention is completely prevented by co-administration of 4.2mg of puromycin/100g body wt. 2. The resting rate of respiration after Ca2+ accumulation by mitochondria from glucagon-treated rats remains low by contrast with that from saline-treated rats. Respiration in the latter mitochondria increased markedly after the Ca2+ accumulation, reflecting the uncoupling action of the ion. 3. Concomitant with the enhanced retention of Ca2+ and low rates of resting respiration by mitochondria from glucagon-treated rats was an increased ability to retain endogenous adenine nucleotides. 4. An investigation of properties of mitochondria known to influence Ca2+ transport revealed a significantly higher concentration of adenine nucleotides but not of Pi in those from glucagon-treated rats. The membrane potential remained unchanged, but the transmembrane pH gradient increased by approx. 10mV, indicating increased alkalinity of the matrix space. 5. Depletion of endogenous adenine nucleotides by Pi treatment in mitochondria from both glucagon-treated and saline-treated rats led to a marked diminution in ability to retain Ca2+. The activity of the adenine nucleotide translocase was unaffected by glucagon treatment of rats in vivo. 6. Although the data are consistent with the argument that the Ca2+-translocation cycle in rat liver mitochondria is a target for glucagon action in vivo, they do not permit conclusions to be drawn about the molecular mechanisms involved in the glucagon-induced alteration to this cycle.

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Mammalian adaptation to extrauterine environment: mitochondrial functional impairment caused by prematurity

Biochemical Journal ◽

10.1042/bj3030855 ◽

1994 ◽

Vol 303 (3) ◽

pp. 855-862 ◽

Cited By ~ 16

Author(s):

C Valcarce ◽

J M Izquierdo ◽

M Chamorro ◽

J M Cuezva

Keyword(s):

Oxidative Phosphorylation ◽

Adenine Nucleotide ◽

Adenine Nucleotides ◽

Coupling Efficiency ◽

Fold Increase ◽

Liver Mitochondria ◽

Postnatal Period ◽

Preterm Neonates ◽

Inner Mitochondrial Membrane ◽

Adenine Nucleotide Pool

In this paper we report that, compared with term rat neonates, both mitochondrial content and function are diminished in liver of preterm neonates (delivered 24 h before full term) compromising cellular energy provision in the postnatal period. In addition, there is a parallel reduction in the content of mRNAs encoding mitochondrial proteins in preterm rats. Also, efficient oxidative phosphorylation is not attained in these pups until 3 h after birth. Although isolated liver mitochondria from preterm neonates show a two-fold increase in F1-ATPase beta-subunit and cytochrome c oxidase activity 1 h after birth, the abnormal coupling efficiency between respiration and oxidative phosphorylation (ADP/O ratio) is due to maintenance of high H(+)-leakage values in the inner mitochondrial membrane. Postnatal reduction of the H+ leak occurs concomitantly with an increase in intra-mitochondrial adenine nucleotide concentration. Accumulation of adenine nucleotides in preterm and term liver mitochondria parallels the postnatal increase in total liver adenine nucleotides. Delayed postnatal induction of adenine biosynthesis most likely accounts for the lower adenine nucleotide pool in the liver of preterm neonates. The delayed postnatal accumulation of adenine nucleotides in mitochondria is thus responsible for the impairment in oxidative phosphorylation displayed by organelles of the preterm liver.

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The Effect of Cold on Platelets. III. Adenine Nucleotide Metabolism After Brief Storage at Cold Temperature

Blood ◽

10.1182/blood.v42.4.557.557 ◽

1973 ◽

Vol 42 (4) ◽

pp. 557-564 ◽

Cited By ~ 7

Author(s):

Herman E. Kattlove ◽

Dorothy Mormino

Keyword(s):

Connective Tissue ◽

Prostaglandin E1 ◽

Room Temperature ◽

Adenine Nucleotide ◽

Platelet Rich Plasma ◽

Adenine Nucleotides ◽

Nucleotide Metabolism ◽

Immunoglobulin M ◽

Release Reaction ◽

Adenine Nucleotide Metabolism

Abstract The effect of cold on platelet adenine nucleotide (PAN) metabolism was studied. Spontaneous aggregation which occurs when chilled platelet-rich plasma (PRP) is simultaneously warmed and stirred was not accompanied by the changes in adenine nucleotides associated with the release reaction. Connective tissue caused the release of the same amount of ADP and conversion of equal amounts of ATP to IMP and hypoxanthine in cold-stored platelets as it did in room temperature stored platelets. However, cold did have an important effect on PAN. In PRP stored at cold (0° C, 3° C) temperatures and warmed up to 37° C in the presence of 3H adenine, there was an increase in the conversion of adenine to its metabolites and ultimately to hypoxanthine as compared to PRP stored at warmer temperatures. This effect could not be prevented by ouabain, prostaglandin E1, antibody to immunoglobulin M or adenosine.

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