Acceleration of adenine nucleotide synthesis de novo during development of cardiac hypertrophy

1972 ◽  
Vol 4 (3) ◽  
pp. 279-282 ◽  
Author(s):  
H Zimmer
Keyword(s):  
Cardiac Hypertrophy ◽  
De Novo ◽  
Adenine Nucleotide ◽  
Nucleotide Synthesis

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.

Adenine nucleotide synthesis in exercising and endurance-trained skeletal muscle

1991 ◽  
Vol 261 (2) ◽  
pp. C342-C347 ◽  
Author(s):  
P. C. Tullson ◽  
R. L. Terjung
Keyword(s):  
De Novo ◽  
Adenine Nucleotide ◽  
Energy State ◽  
High Energy ◽  
Strenuous Exercise ◽  
Muscle Fiber Types ◽  
Fiber Types ◽  
De Novo Synthesis ◽  
Nucleotide Synthesis ◽  
Fast Twitch

Strenuous exercise leads to increased efflux of purine nucleoside and base that should necessitate recovery of adenine nucleotides by either the de novo synthesis or salvage pathway. De novo synthesis of adenine nucleotide was measured in quiescent and contracting muscle of sedentary and exercise-trained rats using an isolated perfused hindquarter preparation. Synthesis rates were assessed by measuring the incorporation of [1-14C]glycine into adenine nucleotide in muscles of both resting and stimulated hindlimbs after 1 h of either low- or high-energy demand isometric contractions. In nonstimulated sedentary and trained muscles, rates of de novo synthesis were similar. The effect of muscle contractions on de novo synthesis varied among muscle fiber types. Contracting, nonfatigued fast-twitch muscle sections showed significant declines in de novo synthesis in both sedentary and trained groups. Rates in slow-twitch red fibers and fatigued fast-twitch white fiber sections were not different from rest. Supplementing the perfusate with 5 mM ribose caused de novo synthesis to rise three- to fourfold in each of the fiber sections. However, the response in synthesis rates due to exercise was similar with or without ribose supplementation. De novo synthesis does not increase during exercise but exhibits an unchanged or reduced rate depending on the expected energy balance within the cell. This would occur if the energy state of muscle exerts significant control over de novo synthesis of adenine nucleotide.

Different response of adenine nucleotide synthesis de novo in kidney and brain during aerobic recovery from anoxia and ischemia

1971 ◽  
Vol 27 (8) ◽  
pp. 876-878 ◽  
Author(s):  
E. Gerlach ◽  
P. Marko ◽  
H. -G. Zimmer ◽  
I. Pechan ◽  
Ch. Trendelenburg
Keyword(s):  
De Novo ◽  
Adenine Nucleotide ◽  
Nucleotide Synthesis ◽  
Different Response

scholarly journals Cellular pyrimidine imbalance triggers mitochondrial DNA–dependent innate immunity

2021 ◽  
Author(s):  
Hans-Georg Sprenger ◽  
Thomas MacVicar ◽  
Amir Bahat ◽  
Kai Uwe Fiedler ◽  
Steffen Hermans ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Cultured Cells ◽  
De Novo ◽  
Metabolic Response ◽  
Interferon Response ◽  
Type I ◽  
Nucleotide Synthesis ◽  
Pyrimidine Synthesis ◽  
Pyrimidine Nucleotide ◽  
De Novo Pyrimidine Synthesis

AbstractCytosolic mitochondrial DNA (mtDNA) elicits a type I interferon response, but signals triggering the release of mtDNA from mitochondria remain enigmatic. Here, we show that mtDNA-dependent immune signalling via the cyclic GMP–AMP synthase‒stimulator of interferon genes‒TANK-binding kinase 1 (cGAS–STING–TBK1) pathway is under metabolic control and is induced by cellular pyrimidine deficiency. The mitochondrial protease YME1L preserves pyrimidine pools by supporting de novo nucleotide synthesis and by proteolysis of the pyrimidine nucleotide carrier SLC25A33. Deficiency of YME1L causes inflammation in mouse retinas and in cultured cells. It drives the release of mtDNA and a cGAS–STING–TBK1-dependent inflammatory response, which requires SLC25A33 and is suppressed upon replenishment of cellular pyrimidine pools. Overexpression of SLC25A33 is sufficient to induce immune signalling by mtDNA. Similarly, depletion of cytosolic nucleotides upon inhibition of de novo pyrimidine synthesis triggers mtDNA-dependent immune responses in wild-type cells. Our results thus identify mtDNA release and innate immune signalling as a metabolic response to cellular pyrimidine deficiencies.

scholarly journals Small-Molecule Screen Identifies De Novo Nucleotide Synthesis as a Vulnerability of Cells Lacking SIRT3

Cell Reports ◽  
2018 ◽  
Vol 22 (8) ◽  
pp. 1945-1955 ◽  
Author(s):  
Karina N. Gonzalez Herrera ◽  
Elma Zaganjor ◽  
Yoshinori Ishikawa ◽  
Jessica B. Spinelli ◽  
Haejin Yoon ◽  
...  
Keyword(s):  
Small Molecule ◽  
De Novo ◽  
Nucleotide Synthesis ◽  
Small Molecule Screen

scholarly journals Intracellular Mg2+regulates ADP phosphorylation and adenine nucleotide synthesis in human erythrocytes

1998 ◽  
Vol 274 (5) ◽  
pp. E920-E927 ◽  
Author(s):  
Sarah Page ◽  
Michael Salem ◽  
Maren R. Laughlin
Keyword(s):  
Adenine Nucleotide ◽  
Phosphoglycerate Kinase ◽  
Pentose Phosphate ◽  
Human Erythrocytes ◽  
Maximal Velocity ◽  
Nucleotide Synthesis ◽  
Ion Concentrations ◽  
Net Flux ◽  
Normal Fluctuations ◽  
Phosphorylation Rate

13C- and31P-NMR were used in methylene blue-treated human erythrocytes to determine the dependence on intracellular Mg2+concentration ([Mg2+]i) of the pentose phosphate pathway (PPP), the glycolytic pathway, and adenine nucleotide synthesis. The PPP flux had an [Mg2+]iat half-maximal velocity ([Mg2+]i,0.5) of 0.02 mM, well below the physiological range (0.2–0.7 mM). Flux through the PPP was reduced at higher [Mg2+]ias flux through phosphofructokinase was increased ([Mg2+]i,0.5= 0.16 mM). [Mg2+]i,0.5of phosphoglycerate kinase flux, which equals net ADP phosphorylation rate, was 0.27 mM, well within the physiological [Mg2+]irange. The rate of adenine nucleotide synthesis from [2-13C]glucose-derived ribose 5-phosphate and exogenous adenine also exhibited dependence on [Mg2+]ibut was not saturable up to 1.6 mM. Therefore, net flux through the PPP and glycolytic pathways in erythrocytes is not strongly dependent on [Mg2+]iat physiological ion concentrations, but both ADP phosphorylation and adenine nucleotide synthesis are likely to be regulated by normal fluctuations in [Mg2+]i.

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