scholarly journals A cyanosulfidic origin of the Krebs cycle

2021 ◽  
Vol 7 (33) ◽  
pp. eabh3981
Author(s):  
Dougal J. Ritson
Keyword(s):  
Amino Acids ◽  
Hydrogen Cyanide ◽  
Present Report ◽  
Krebs Cycle ◽  
Glyoxylate Shunt ◽  
Uv Photolysis ◽  
Succinate Semialdehyde ◽  
Almost All

The centrality of the Krebs cycle in metabolism has long been interpreted as evidence of its antiquity, and consequently, questions regarding its provenance, and whether it initially functioned as a cycle or not, have received much attention. The present report shows that prebiotic oxidation of α-hydroxy carboxylates can be achieved by UV photolysis of a simple geochemical species (HS−), which leads to α-oxo carboxylates that feature in the Krebs cycle and glyoxylate shunt. Further reaction of these products leads to almost all intermediates of the Krebs cycle proper, succinate semialdehyde bypass, and glyoxylate shunt. Fumarate, the missing Krebs cycle component, and the required α-hydroxy carboxylates can be provided by a highly related hydrogen cyanide chemistry, which also provides precursors for amino acids, nucleotides, and phospholipids.

scholarly journals An appeal to magic? The discovery of a non-enzymatic metabolism and its role in the origins of life

2018 ◽  
Vol 475 (16) ◽  
pp. 2577-2592 ◽  
Author(s):  
Markus Ralser
Keyword(s):  
Amino Acids ◽  
Metabolic Pathway ◽  
Metal Cation ◽  
Hydrogen Cyanide ◽  
Metabolic Pathways ◽  
Co2 Fixation ◽  
Enzymatic Reaction ◽  
Krebs Cycle ◽  
Pentose Phosphate ◽  
Long Time

Until recently, prebiotic precursors to metabolic pathways were not known. In parallel, chemistry achieved the synthesis of amino acids and nucleotides only in reaction sequences that do not resemble metabolic pathways, and by using condition step changes, incompatible with enzyme evolution. As a consequence, it was frequently assumed that the topological organisation of the metabolic pathway has formed in a Darwinian process. The situation changed with the discovery of a non-enzymatic glycolysis and pentose phosphate pathway. The suite of metabolism-like reactions is promoted by a metal cation, (Fe(II)), abundant in Archean sediment, and requires no condition step changes. Knowledge about metabolism-like reaction topologies has accumulated since, and supports non-enzymatic origins of gluconeogenesis, the S-adenosylmethionine pathway, the Krebs cycle, as well as CO2 fixation. It now feels that it is only a question of time until essential parts of metabolism can be replicated non-enzymatically. Here, I review the ‘accidents’ that led to the discovery of the non-enzymatic glycolysis, and on the example of a chemical network based on hydrogen cyanide, I provide reasoning why metabolism-like non-enzymatic reaction topologies may have been missed for a long time. Finally, I discuss that, on the basis of non-enzymatic metabolism-like networks, one can elaborate stepwise scenarios for the origin of metabolic pathways, a situation that increasingly renders the origins of metabolism a tangible problem.

Hydrogen Cyanide Polymers from the Impact of Comet P/Shoemaker-Levy 9 on Jupiter

1997 ◽  
Vol 161 ◽  
pp. 179-187
Author(s):  
Clifford N. Matthews ◽  
Rose A. Pesce-Rodriguez ◽  
Shirley A. Liebman
Keyword(s):  
Amino Acids ◽  
Solar System ◽  
Hydrogen Cyanide ◽  
Nitrogen Heterocycles ◽  
Laboratory Studies ◽  
Heterogeneous Solids ◽  
The Many ◽  
Comet Halley ◽  
The Impact ◽  
By Products

AbstractHydrogen cyanide polymers – heterogeneous solids ranging in color from yellow to orange to brown to black – may be among the organic macromolecules most readily formed within the Solar System. The non-volatile black crust of comet Halley, for example, as well as the extensive orangebrown streaks in the atmosphere of Jupiter, might consist largely of such polymers synthesized from HCN formed by photolysis of methane and ammonia, the color observed depending on the concentration of HCN involved. Laboratory studies of these ubiquitous compounds point to the presence of polyamidine structures synthesized directly from hydrogen cyanide. These would be converted by water to polypeptides which can be further hydrolyzed to α-amino acids. Black polymers and multimers with conjugated ladder structures derived from HCN could also be formed and might well be the source of the many nitrogen heterocycles, adenine included, observed after pyrolysis. The dark brown color arising from the impacts of comet P/Shoemaker-Levy 9 on Jupiter might therefore be mainly caused by the presence of HCN polymers, whether originally present, deposited by the impactor or synthesized directly from HCN. Spectroscopic detection of these predicted macromolecules and their hydrolytic and pyrolytic by-products would strengthen significantly the hypothesis that cyanide polymerization is a preferred pathway for prebiotic and extraterrestrial chemistry.

Inter-residue interactions in alpha-helical transmembrane proteins

2018 ◽  
Vol 35 (15) ◽  
pp. 2578-2584 ◽  
Author(s):  
Eduardo Mayol ◽  
Mercedes Campillo ◽  
Arnau Cordomí ◽  
Mireia Olivella
Keyword(s):  
Membrane Proteins ◽  
Present Report ◽  
Protein Structures ◽  
Transmembrane Proteins ◽  
Globular Proteins ◽  
Supplementary Information ◽  
Backbone Carbonyl ◽  
Composition Characteristic ◽  
Almost All ◽  
Residue Composition

Abstract Motivation The number of available membrane protein structures has markedly increased in the last years and, in parallel, the reliability of the methods to detect transmembrane (TM) segments. In the present report, we characterized inter-residue interactions in α-helical membrane proteins using a dataset of 3462 TM helices from 430 proteins. This is by far the largest analysis published to date. Results Our analysis of residue–residue interactions in TM segments of membrane proteins shows that almost all interactions involve aliphatic residues and Phe. There is lack of polar–polar, polar–charged and charged–charged interactions except for those between Thr or Ser sidechains and the backbone carbonyl of aliphatic and Phe residues. The results are discussed in the context of the preferences of amino acids to be in the protein core or exposed to the lipid bilayer and to occupy specific positions along the TM segment. Comparison to datasets of β-barrel membrane proteins and of α-helical globular proteins unveils the specific patterns of interactions and residue composition characteristic of α-helical membrane proteins that are the clue to understanding their structure. Availability and implementation Results data and datasets used are available at http://lmc.uab.cat/TMalphaDB/interactions.php. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Accumulation of amino acids by the perfused rat liver in the presence of ethanol

1973 ◽  
Vol 134 (3) ◽  
pp. 697-705 ◽  
Author(s):  
Hans A. Krebs ◽  
Reginald Hems ◽  
Patricia Lund
Keyword(s):  
Amino Acids ◽  
Rat Liver ◽  
Major Effect ◽  
Major Product ◽  
Control Mechanisms ◽  
Perfused Rat Liver ◽  
Carbamoyl Phosphate ◽  
Lactate Formation ◽  
Gluconeogenesis From Alanine ◽  
Almost All

1. The rate of gluconeogenesis from alanine in the perfused rat liver is affected by the presence of other metabolizable substances, especially fatty acids, ornithine and ethanol. Gluconeogenesis is accelerated by oleate and by ornithine. When both oleate and ornithine were present the acceleration was greater than expected on the basis of mere additive effects. 2. Much NH3 and some urea were formed from alanine when no ornithine was added. With ornithine almost all the nitrogen released from alanine appeared as urea. 3. Lactate was a major product of alanine metabolism. Addition of oleate, and especially of oleate plus ornithine, decreased lactate formation. 4. Ethanol had no major effect on gluconeogenesis from alanine when this was the sole added precursor. Gluconeogenesis was strongly inhibited (87%) when oleate was also added, but ethanol greatly accelerated gluconeogenesis when ornithine was added together with alanine. 5. In the absence of ethanol the alanine carbon and alanine nitrogen removed were essentially recovered in the form of glucose, lactate, pyruvate, NH3 and urea. 6. In the presence of ethanol the balance of both alanine carbon and alanine nitrogen showed substantial deficits. These deficits were largely accounted for by the formation of aspartate and glutamine, the formation of which was increased two- to three-fold. 7. When alanine was replaced by lactate plus NH4Cl, ethanol also caused a major accumulation of amino acids, especially of aspartate and alanine. 8. Earlier apparently discrepant results on the effects of ethanol on gluconeogenesis from alanine are explained by the fact that under well defined conditions ethanol can inhibit, or accelerate, or be without major effect on the rate of gluconeogenesis. 9. It is pointed out that in the synthesis of urea through the ornithine cycle half of the nitrogen must be supplied in the form of asparate and half in the form of carbamoyl phosphate. The accumulation of aspartate and other amino acids suggests that ethanol interferes with the control mechanisms which regulate the stoicheiometric formation of aspartate and carbamoyl phosphate.

scholarly journals Expression of 3 beta-hydroxysteroid dehydrogenase/isomerase in the female rat pituitary

2000 ◽  
Vol 166 (1) ◽  
pp. 95-101 ◽  
Author(s):  
S Vidal ◽  
A Roman ◽  
L Moya ◽  
K Kovacs
Keyword(s):  
Present Report ◽  
Hydroxysteroid Dehydrogenase ◽  
Anterior Lobe ◽  
Female Rats ◽  
Endocrine Function ◽  
Pars Intermedia ◽  
Posterior Lobe ◽  
Female Rat ◽  
Target Organs ◽  
Almost All

3 beta-Hydroxysteroid dehydrogenase/isomerase (3 beta-HSD) catalyses an essential step in the biosynthesis of steroid hormones and is widely distributed in peripheral steroid target organs. The present report describes for first time the expression of this enzyme in the pituitary of female rats. Immunohistochemistry at the light microscopic level was performed on pro-oestrous and ovariectomized rat pituitaries. Immunoreactive cells were scattered and randomly distributed throughout the anterior lobe, whereas cells located in the posterior lobe and pars intermedia were immunonegative. Differences were observed in cell morphology and in the number of 3 beta-HSD-immunopositive cells between ovariectomized and pro-oestrous female rat pituitaries, suggesting that steroidogenic activity is affected by ovarian endocrine function. Apart from adenohypophyseal immunoreactive cells, 3 beta-HSD immunopositivity was also noted in endothelial cells of almost all pituitary capillaries located in the anterior and posterior lobes.

BINDING OF 17-SUBSTITUTED 16-NITRILE 16,17-SECOESTRANE COMPOUNDS TO ESTROGEN RECEPTORS – „IN VITRO“ AND „IN SILICO“ STUDY

2021 ◽  
Author(s):  
Suzana S. Jovanović-Šanta ◽  
◽  
Esma Isenović ◽  
Julijana A. Petrović ◽  
Yaraslau U. Dzichenka
Keyword(s):  
Amino Acids ◽  
Estrogen Receptors ◽  
Nuclear Translocation ◽  
Binding Mode ◽  
High Rate ◽  
Dynamics Simulation ◽  
Breast Cancers ◽  
Number Of Binding Sites ◽  
Almost All

About 75% of breast cancers express estrogen receptors (ERs), which is a good base for an efficient endocrine therapy. This gives the opportunity for the treatment of patients with antiestrogens, compounds that bind to the ERs and thus compete to estradiol (E2), preventing its action in progression of estrogen-depending cancers. Here we present results of testing the effect of the modified steroids, namely 17-substituted 16-nitrile 16,17-secoestrane compounds on the E2-ER complex forming, its stability, nuclear translocation and binding to DNA. Almost all compounds in moderate to high rate induced lower forming of this complex, destabilizing it – they increased Kd of this complex and decreased number of binding sites. Complex formed in the presence of some test secosteroids could pass to the nucleus, while other compounds inhibited translocation. In the presence of some compounds binding of the formed complex E2-ER to DNA was noticed. Docking followed molecular dynamics simulation was performed to reveal binding mode of E2 to ER in the presence of test secosteroids. Amino acids important for binding process and complex stabilization were detected. Analysis of the simulation data allowed identifying key amino acids and type of binding of the secoestrane compounds, important for high affinity binding of the steroidal compounds.

scholarly journals The effect of hypermethylation on the functional properties of transfer ribonucleic acid. Formation of aminoacyl-transfer-ribonucleic acid

1969 ◽  
Vol 114 (2) ◽  
pp. 429-435 ◽  
Author(s):  
David J. Pillinger ◽  
John Hay ◽  
Ernest Borek
Keyword(s):  
Amino Acids ◽  
Ribonucleic Acid ◽  
Control Sample ◽  
Transfer Rna ◽  
E Coli ◽  
Functional Sites ◽  
The Individual ◽  
Almost All ◽  
Aminoacyl Transfer ◽  
Kinetics Of

1. The ability of chemically hypermethylated Escherichia coli B transfer RNA to accept 19 amino acids was studied and the results were compared with those obtained with a control sample of E. coli B transfer RNA incubated under similar conditions in the absence of methylating agent. 2. There is a marked decrease in the ability of the modified transfer RNA to accept amino acids in almost all instances. 3. The acceptance of cysteine appears to be unique in that it is enhanced in the hypermethylated transfer RNA. 4. More detailed studies on the kinetics of acceptance for six amino acids is presented, emphasizing the variation in response of the individual amino acids. 5. Increasing hypermethylation causes a progressive decrease in the amino acid acceptance. 6. The results are discussed in terms of methylation at functional sites within the transfer RNA and possible conformational alterations to the structure of the macromolecule.

scholarly journals The Effect of Mineral Nutrient Deficiency on the Content of free Amino Acids in Setaria Sphacelata

1972 ◽  
Vol 25 (1) ◽  
pp. 77 ◽  
Author(s):  
RD Court ◽  
WT Williams ◽  
MP Hegarty
Keyword(s):  
Amino Acids ◽  
Free Amino Acids ◽  
Free Amino ◽  
Nitrogen Deficiency ◽  
Nutrient Deficiency ◽  
Leaf Nitrogen ◽  
Mineral Nutrient ◽  
Nutrient Deficiencies ◽  
Setaria Sphacelata ◽  
Almost All

The effects of several single mineral nutrient deficiencies on the free amino acid composition of S. sphacelata, grown in water culture, have been examined. Most deficiencies result in an accumulation of the free amino acids. Severe copper deficiency causes a large increase in the alanine content of the leaf. Nitrogen deficiency causes decreases in almost all amino acids.

scholarly journals Polyamines in Microalgae: Something Borrowed, Something New

Marine Drugs ◽  
2018 ◽  
Vol 17 (1) ◽  
pp. 1 ◽  
Author(s):  
Hung-Yun Lin ◽  
Han-Jia Lin
Keyword(s):  
Amino Acids ◽  
Primary Production ◽  
Metabolic Pathways ◽  
Food Source ◽  
Biotechnological Applications ◽  
Evolutionary Origins ◽  
Microbial Ecosystems ◽  
Polyamine Content ◽  
Synthetic Routes ◽  
Almost All

Microalgae of different evolutionary origins are typically found in rivers, lakes, and oceans, providing more than 45% of global primary production. They provide not only a food source for animals, but also affect microbial ecosystems through symbioses with microorganisms or secretion of some metabolites. Derived from amino acids, polyamines are present in almost all types of organisms, where they play important roles in maintaining physiological functions or against stress. Microalgae can produce a variety of distinct polyamines, and the polyamine content is important to meet the physiological needs of microalgae and may also affect other species in the environment. In addition, some polyamines produced by microalgae have medical or nanotechnological applications. Previous studies on several types of microalgae have indicated that the putative polyamine metabolic pathways may be as complicated as the genomes of these organisms, which contain genes originating from plants, animals, and even bacteria. There are also several novel polyamine synthetic routes in microalgae. Understanding the nature of polyamines in microalgae will not only improve our knowledge of microalgal physiology and ecological function, but also provide valuable information for biotechnological applications.

Response to osmotic stimuli in mesangial cells: role of system A transporter

1994 ◽  
Vol 267 (5) ◽  
pp. C1493-C1500 ◽  
Author(s):  
A. Yamauchi ◽  
A. Miyai ◽  
K. Yokoyama ◽  
T. Itoh ◽  
T. Kamada ◽  
...  
Keyword(s):  
Amino Acids ◽  
Mesangial Cells ◽  
Isobutyric Acid ◽  
Maximal Velocity ◽  
Transport Activity ◽  
Hypertonic Medium ◽  
Neutral Amino Acids ◽  
System A ◽  
Almost All

It has been suggested that mesangial cells have an osmoregulatory mechanism like that of renal medullary cells, such as intracellular accumulation of polyols in response to hypertonicity. We examined osmoregulatory role of neutral amino acids transported by system A in cultured mesangial cells. The contents of almost all amino acids increased under hypertonic conditions to more than twice the value in isotonic cells. In hypertonic cells, the system A transport activity, measured by Na(+)-dependent 2-(methylamino)isobutyric acid (MeAIB) uptake, was 3.8-fold the uptake in isotonic cells, reaching a maximum 16 h after the switch to hypertonic medium. The response to hypertonicity was the result of an increase in maximal velocity without change in Michaelis constant and was dependent on RNA and protein synthesis. When medium osmolality decreased from hypertonic to isotonic, MeAIB uptake reverted to the isotonic level within 16 h and a large transient efflux of L-proline occurred within 10 min. These results suggest that mesangial cells respond to extracellular hypertonicity by increasing system A transport activity and neutral amino acids can function as compatible osmolytes in mesangial cells.

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