scholarly journals A prebiotic basis for ATP as the universal energy currency

2021 ◽  
Author(s):  
Silvana Pinna ◽  
Cäcilia Kunz ◽  
Stuart Harrison ◽  
Sean F. Jordan ◽  
John Ward ◽  
...  
Keyword(s):  
Prebiotic Chemistry ◽  
Atp Hydrolysis ◽  
Early Stage ◽  
Phosphate Metabolism ◽  
Acetyl Phosphate ◽  
Carbamoyl Phosphate ◽  
Purine Synthesis ◽  
Adenine Ring ◽  
Substrate Level ◽  
Principal Energy

AbstractATP is universally conserved as the principal energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep conservation suggests that ATP arose at an early stage of biochemical evolution. Yet purine synthesis requires six phosphorylation steps linked to ATP hydrolysis. This autocatalytic requirement for ATP to synthesize ATP implies the need for an earlier prebiotic ATP-equivalent, which could drive protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically with ATP rather than other nucleotide triphosphates, remains a mystery. Here we show that the deep conservation of ATP reflects its prebiotic chemistry in relation to another universally conserved intermediate, acetyl phosphate, which bridges between thioester and phosphate metabolism by linking acetyl CoA to the substrate-level phosphorylation of ADP. We confirm earlier results showing that acetyl phosphate can phosphorylate ADP to ATP at nearly 20 % yield in water in the presence of Fe3+ ions. We then show that Fe3+ and acetyl phosphate are surprisingly favoured: a panel of other prebiotically relevant ions and minerals did not catalyze ADP phosphorylation; nor did a number of other potentially prebiotic phosphorylating agents. Only carbamoyl phosphate showed some modest phosphorylating activity. Critically, we show that acetyl phosphate does not phosphorylate other nucleotide diphosphates or free pyrophosphate in water. The phosphorylation of ADP monomers seems to be favoured by the interaction between the N6 amino group on the adenine ring with Fe3+ coupled to acetyl phosphate. Our findings suggest that the reason ATP is universally conserved across life is that its formation is chemically favoured in aqueous solution under mild prebiotic conditions.

Skeletal muscle phosphate metabolism abnormalities in volume-overload experimental heart failure

1994 ◽  
Vol 267 (6) ◽  
pp. H2186-H2192 ◽  
Author(s):  
Z. Chati ◽  
F. Zannad ◽  
C. Michel ◽  
B. Lherbier ◽  
P. M. Mertes ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Early Stage ◽  
Volume Overload ◽  
Significant Rise ◽  
Initial Slope ◽  
Heart Weight ◽  
Resonance Spectroscopy ◽  
Phosphate Metabolism

We studied skeletal muscle phosphate metabolism abnormalities to examine their contribution at an early stage of congestive heart failure (CHF) in rats with aortocaval fistula (ACF) 4 wk after the procedure. In a group of 26 rats (13 with ACF and 13 sham operated), we assessed the degree of CHF. The ACF produced a significant rise in heart weight and plasma atrial natriuretic peptide. In a second group of 26 rats (13 ACF and 13 sham operated), we performed 31P-magnetic resonance spectroscopy in the gastrocnemius muscle during motor activity produced by electrical stimulation. The rate of phosphocreatine depletion, expressed by its initial slope, was higher in the ACF rats compared with controls (0.078 +/- 0.01 vs. 0.041 +/- 0.007; P < 0.03). pH and ATP decreased and phosphodiesters increased in all rats during electrical stimulation, with no difference between ACF rats and controls. The kinetics of phosphocreatine recovery were not different between ACF rats and controls. Together with previous studies, our present results suggest that muscle metabolism abnormalities in CHF may vary according to the experimental model and may be observed early in the course of the disease.

scholarly journals Acylation of carcinogenic hydroxamic acids by carbamoyl phosphate to form reactive esters

1971 ◽  
Vol 124 (1) ◽  
pp. 69-74 ◽  
Author(s):  
P D. Lotlikar ◽  
L Luha
Keyword(s):  
Hydroxamic Acids ◽  
Phosphate Concentration ◽  
Acetyl Phosphate ◽  
Acylating Agent ◽  
Carbamoyl Phosphate ◽  
Acetyl Coa ◽  
Ph Optimum ◽  
Lag Period ◽  
Reactive N ◽  
Derivatives Of

1. Acylation of 2-(N-hydroxyacetamido)fluorene and several other aromatic hydroxamic acids by carbamoyl phosphate was studied and compared with the acylating activity of acetyl-CoA. Acetyl phosphate was also studied. 2. The carbamoylation reaction had a pH optimum of 4.5. The reaction had a lag period of 1h and was then linear for 4h. This linearity ranged between 0.5mm- and 8mm-carbamoyl phosphate concentration. 3. At pH7.5, acetyl-CoA was the most powerful acylating agent. Acetyl phosphate was a weaker acylating agent than either of the others. 4. Among the various hydroxamic acids tested with acetyl-CoA and carbamoyl phosphate at pH.7.5, 2-(N-hydroxyacetamido)fluorene was the most reactive. On the other hand the less reactive N-hydroxy derivatives of 2-acetamidonaphthalene, 2-acetamidophenanthrene and 4-acetamidostilbene reacted severalfold more with carbamoyl phosphate than with acetyl-CoA. 5. It is suggested that carbamoylation of aromatic hydroxamic acids might be one of the final activation steps in carcinogenesis by these compounds.

scholarly journals Non-enzymic protein phosphorylation. Phosphorylation of 6-phosphogluconate dehydrogenase by acyl phosphates

1982 ◽  
Vol 203 (2) ◽  
pp. 401-404 ◽  
Author(s):  
F Dallocchio ◽  
M Matteuzzi ◽  
T Bellini
Keyword(s):  
Protein Phosphorylation ◽  
Candida Utilis ◽  
Kinetic Properties ◽  
Acetyl Phosphate ◽  
Carbamoyl Phosphate ◽  
Phosphogluconate Dehydrogenase ◽  
Protein Inactivation

Incubation of 6-phosphogluconate dehydrogenase from Candida utilis with either acetyl phosphate, 1,3-diphosphoglycerate or carbamoyl phosphate results in the phosphorylation of the protein. The binding of one phosphate residue per enzyme subunit does not affect significantly the kinetic properties, but makes the enzyme less reactive toward thiol reagents, trypsin and pyridoxal 5′-phosphate. We suggest indicate that: (1) 6-phosphogluconate dehydrogenase from C. utilis is phosphorylated non-enzymically by physiological acyl phosphates and (2) the phosphorylation of the enzyme modifies the rate of protein inactivation.

scholarly journals On the origin of biochemistry at an alkaline hydrothermal vent

2006 ◽  
Vol 362 (1486) ◽  
pp. 1887-1926 ◽  
Author(s):  
William Martin ◽  
Michael J Russell
Keyword(s):  
Hydrothermal Vent ◽  
Proton Gradient ◽  
Metabolic Energy ◽  
Acetyl Phosphate ◽  
Carbamoyl Phosphate ◽  
Acetyl Coa ◽  
Metabolic Systems ◽  
Acetyl Coa Pathway ◽  
Pyruvate Synthase ◽  
Carbonyl Sulphide

A model for the origin of biochemistry at an alkaline hydrothermal vent has been developed that focuses on the acetyl-CoA (Wood–Ljungdahl) pathway of CO 2 fixation and central intermediary metabolism leading to the synthesis of the constituents of purines and pyrimidines. The idea that acetogenesis and methanogenesis were the ancestral forms of energy metabolism among the first free-living eubacteria and archaebacteria, respectively, stands in the foreground. The synthesis of formyl pterins, which are essential intermediates of the Wood–Ljungdahl pathway and purine biosynthesis, is found to confront early metabolic systems with steep bioenergetic demands that would appear to link some, but not all, steps of CO 2 reduction to geochemical processes in or on the Earth's crust. Inorganically catalysed prebiotic analogues of the core biochemical reactions involved in pterin-dependent methyl synthesis of the modern acetyl-CoA pathway are considered. The following compounds appear as probable candidates for central involvement in prebiotic chemistry: metal sulphides, formate, carbon monoxide, methyl sulphide, acetate, formyl phosphate, carboxy phosphate, carbamate, carbamoyl phosphate, acetyl thioesters, acetyl phosphate, possibly carbonyl sulphide and eventually pterins. Carbon might have entered early metabolism via reactions hardly different from those in the modern Wood–Ljungdahl pathway, the pyruvate synthase reaction and the incomplete reverse citric acid cycle. The key energy-rich intermediates were perhaps acetyl thioesters, with acetyl phosphate possibly serving as the universal metabolic energy currency prior to the origin of genes. Nitrogen might have entered metabolism as geochemical NH 3 via two routes: the synthesis of carbamoyl phosphate and reductive transaminations of α-keto acids. Together with intermediates of methyl synthesis, these two routes of nitrogen assimilation would directly supply all intermediates of modern purine and pyrimidine biosynthesis. Thermodynamic considerations related to formyl pterin synthesis suggest that the ability to harness a naturally pre-existing proton gradient at the vent–ocean interface via an ATPase is older than the ability to generate a proton gradient with chemistry that is specified by genes.

scholarly journals The conversion of formate into purines stimulates mTORC1 leading to CAD-dependent activation of pyrimidine synthesis

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Jacqueline Tait-Mulder ◽  
Kelly Hodge ◽  
David Sumpton ◽  
Sara Zanivan ◽  
Alexei Vazquez
Keyword(s):  
Enzymatic Activity ◽  
Metabolic Profiling ◽  
Carbamoyl Phosphate Synthetase ◽  
Carbamoyl Phosphate ◽  
Metabolic Switch ◽  
Purine Synthesis ◽  
Pyrimidine Synthesis ◽  
Mechanistic Target Of Rapamycin ◽  
Hypermetabolic State ◽  
Mtor Signalling

Abstract Background Mitochondrial serine catabolism to formate induces a metabolic switch to a hypermetabolic state with high rates of glycolysis, purine synthesis and pyrimidine synthesis. While formate is a purine precursor, it is not clear how formate induces pyrimidine synthesis. Methods Here we combine phospho-proteome and metabolic profiling to determine how formate induces pyrimidine synthesis. Results We discover that formate induces phosphorylation of carbamoyl phosphate synthetase (CAD), which is known to increase CAD enzymatic activity. Mechanistically, formate induces mechanistic target of rapamycin complex 1 (mTORC1) activity as quantified by phosphorylation of its targets S6, 4E-BP1, S6K1 and CAD. Treatment with the allosteric mTORC1 inhibitor rapamycin abrogates CAD phosphorylation and pyrimidine synthesis induced by formate. Furthermore, we show that the formate-dependent induction of mTOR signalling and CAD phosphorylation is dependent on an increase in purine synthesis. Conclusions We conclude that formate activates mTORC1 and induces pyrimidine synthesis via the mTORC1-dependent phosphorylation of CAD.

Development of contractile dysfunction in rat heart failure: hierarchy of cellular events

2007 ◽  
Vol 293 (1) ◽  
pp. R284-R292 ◽  
Author(s):  
Marcel C. G. Daniels ◽  
Taihei Naya ◽  
Veronica L. M. Rundell ◽  
Pieter P. de Tombe
Keyword(s):  
Heart Failure ◽  
Atp Hydrolysis ◽  
Early Stage ◽  
Left Ventricular ◽  
Hydrolysis Rate ◽  
Cellular Mechanisms ◽  
Twitch Force ◽  
Protein Levels ◽  
Cellular Events ◽  
End Stage

The cellular mechanisms underlying the development of congestive heart failure (HF) are not well understood. Accordingly, we studied myocardial function in isolated right ventricular trabeculae from rats in which HF was induced by left ventricular myocardial infarction (MI). Both early-stage (12 wk post-MI; E-pMI) and late, end-stage HF (28 wk post-Mi; L-pMI) were studied. HF was associated with decreased sarcoplasmic reticulum Ca2+ ATPase protein levels (28% E-pMI; 52% L-pMI). HF affected neither sodium/calcium exchange, ryanodine receptor, nor phospholamban protein levels. Twitch force at saturating extracellular [Ca2+] was depressed in HF (30% E-pMI; 38% L-pMI), concomitant with a marked increase in sensitivity of twitch force toward extracellular [Ca2+] (26% E-pMI; 68% L-pMI). Ca2+-saturated myofilament force development in skinned trabeculae was unchanged in E-pMI but significantly depressed in L-pMI (45%). Tension-dependent ATP hydrolysis rate was depressed in L-pMI (49%), but not in E-pMI. Our results suggest a hierarchy of cellular events during the development of HF, starting with altered calcium homeostasis during the early phase followed by myofilament dysfunction at end-stage HF.

scholarly journals Role of water activity on the rates of acetyl phosphate and ATP hydrolysis

FEBS Letters ◽  
1988 ◽  
Vol 232 (1) ◽  
pp. 73-77 ◽  
Author(s):  
Leopoldo de Meis ◽  
Valdecir Antunes Suzano
Keyword(s):  
Water Activity ◽  
Atp Hydrolysis ◽  
Acetyl Phosphate
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