Synthesis and Breakdown of the Universal Precursors to Biological Metabolism Promoted by Ferrous Iron

2018 ◽  
Author(s):  
Kamila B. Muchowska ◽  
Sreejith Jayasree VARMA ◽  
Joseph Moran
Keyword(s):  
Amino Acids ◽  
Chemical Reaction ◽  
Metabolic Pathways ◽  
Ferrous Iron ◽  
Reaction Network ◽  
Tca Cycle ◽  
Chemical Reaction Network ◽  
Metabolic Precursors ◽  
Tca Cycle Intermediates

How core biological metabolism initiated and why it uses the intermediates, reactions and pathways that it does remains unclear. Life builds its molecules from CO<sub>2 </sub>and breaks them down to CO<sub>2 </sub>again through the intermediacy of just five metabolites that act as the hubs of biochemistry. Here, we describe a purely chemical reaction network promoted by Fe<sup>2+ </sup>in which aqueous pyruvate and glyoxylate, two products of abiotic CO<sub>2 </sub>reduction, build up nine of the eleven TCA cycle intermediates, including all five universal metabolic precursors. The intermediates simultaneously break down to CO<sub>2 </sub>in a life-like regime resembling biological anabolism and catabolism. Introduction of hydroxylamine and Fe<sup>0 </sup>produces four biological amino acids. The network significantly overlaps the TCA/rTCA and glyoxylate cycles and may represent a prebiotic precursor to these core metabolic pathways.

Synthesis and Breakdown of the Universal Precursors to Biological Metabolism Promoted by Ferrous Iron

2018 ◽  
Author(s):  
Kamila B. Muchowska ◽  
Sreejith Jayasree VARMA ◽  
Joseph Moran
Keyword(s):  
Amino Acids ◽  
Chemical Reaction ◽  
Metabolic Pathways ◽  
Ferrous Iron ◽  
Reaction Network ◽  
Tca Cycle ◽  
Chemical Reaction Network ◽  
Metabolic Precursors ◽  
Tca Cycle Intermediates

How core biological metabolism initiated and why it uses the intermediates, reactions and pathways that it does remains unclear. Life builds its molecules from CO<sub>2 </sub>and breaks them down to CO<sub>2 </sub>again through the intermediacy of just five metabolites that act as the hubs of biochemistry. Here, we describe a purely chemical reaction network promoted by Fe<sup>2+ </sup>in which aqueous pyruvate and glyoxylate, two products of abiotic CO<sub>2 </sub>reduction, build up nine of the eleven TCA cycle intermediates, including all five universal metabolic precursors. The intermediates simultaneously break down to CO<sub>2 </sub>in a life-like regime resembling biological anabolism and catabolism. Introduction of hydroxylamine and Fe<sup>0 </sup>produces four biological amino acids. The network significantly overlaps the TCA/rTCA and glyoxylate cycles and may represent a prebiotic precursor to these core metabolic pathways.

scholarly journals Profiles of Secondary Metabolites (Phenolic Acids, Carotenoids, Anthocyanins, and Galantamine) and Primary Metabolites (Carbohydrates, Amino Acids, and Organic Acids) during Flower Development in Lycoris radiata

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 248
Author(s):  
Chang Ha Park ◽  
Hyeon Ji Yeo ◽  
Ye Jin Kim ◽  
Bao Van Nguyen ◽  
Ye Eun Park ◽  
...  
Keyword(s):  
Amino Acids ◽  
Secondary Metabolites ◽  
Organic Acids ◽  
Phenolic Acids ◽  
Flower Development ◽  
Developmental Stages ◽  
Tca Cycle ◽  
Primary And Secondary Metabolites ◽  
Hydrophilic Compounds ◽  
Tca Cycle Intermediates

This study aimed to elucidate the variations in primary and secondary metabolites during Lycorisradiata flower development using high performance liquid chromatography (HPLC) and gas chromatography time-of-flight mass spectrometry (GC-TOFMS). The result showed that seven carotenoids, seven phenolic acids, three anthocyanins, and galantamine were identified in the L. radiata flowers. Most secondary metabolite levels gradually decreased according to the flower developmental stages. A total of 51 metabolites, including amines, sugars, sugar intermediates, sugar alcohols, amino acids, organic acids, phenolic acids, and tricarboxylic acid (TCA) cycle intermediates, were identified and quantified using GC-TOFMS. Among the hydrophilic compounds, most amino acids increased during flower development; in contrast, TCA cycle intermediates and sugars decreased. In particular, glutamine, asparagine, glutamic acid, and aspartic acid, which represent the main inter- and intracellular nitrogen carriers, were positively correlated with the other amino acids and were negatively correlated with the TCA cycle intermediates. Furthermore, quantitation data of the 51 hydrophilic compounds were subjected to partial least-squares discriminant analyses (PLS-DA) to assess significant differences in the metabolites of L. radiata flowers from stages 1 to 4. Therefore, this study will serve as the foundation for a biochemical approach to understand both primary and secondary metabolism in L. radiata flower development.

scholarly journals Intracellular Fate of Universally Labelled 13C Isotopic Tracers of Glucose and Xylose in Central Metabolic Pathways of Xanthomonas oryzae

Metabolites ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 66 ◽  
Author(s):  
Manu Shree ◽  
Shyam K. Masakapalli
Keyword(s):  
Amino Acids ◽  
Metabolic Pathways ◽  
Metabolic Networks ◽  
Tca Cycle ◽  
Xanthomonas Oryzae ◽  
Flux Analysis ◽  
Isotopic Tracers ◽  
Feeding Experiments ◽  
The Tca Cycle ◽  
Metabolic Route

The goal of this study is to map the metabolic pathways of poorly understood bacterial phytopathogen, Xanthomonas oryzae (Xoo) BXO43 fed with plant mimicking media XOM2 containing glutamate, methionine and either 40% [13C5] xylose or 40% [13C6] glucose. The metabolic networks mapped using the KEGG mapper and the mass isotopomer fragments of proteinogenic amino acids derived from GC-MS provided insights into the activities of Xoo central metabolic pathways. The average 13C in histidine, aspartate and other amino acids confirmed the activities of PPP, the TCA cycle and amino acid biosynthetic routes, respectively. The similar labelling patterns of amino acids (His, Ala, Ser, Val and Gly) from glucose and xylose feeding experiments suggests that PPP would be the main metabolic route in Xoo. Owing to the lack of annotated gene phosphoglucoisomerase in BXO43, the 13C incorporation in alanine could not be attributed to the competing pathways and hence warrants additional positional labelling experiments. The negligible presence of 13C incorporation in methionine brings into question its potential role in metabolism and pathogenicity. The extent of the average 13C labelling in several amino acids highlighted the contribution of pre-existing pools that need to be accounted for in 13C-flux analysis studies. This study provided the first qualitative insights into central carbon metabolic pathway activities in Xoo.

scholarly journals Lactate oxidative phosphorylation by annulus fibrosus cells: evidence for lactate-dependent metabolic symbiosis in intervertebral discs

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Dong Wang ◽  
Robert Hartman ◽  
Chao Han ◽  
Chao-ming Zhou ◽  
Brandon Couch ◽  
...  
Keyword(s):  
Amino Acids ◽  
Lactic Acid ◽  
Oxidative Phosphorylation ◽  
Intervertebral Disc ◽  
Annulus Fibrosus ◽  
Tca Cycle ◽  
Heavy Isotope ◽  
In Vivo Models ◽  
Disc Tissue ◽  
Tca Cycle Intermediates

Abstract Background Intervertebral disc degeneration contributes to low back pain. The avascular intervertebral disc consists of a central hypoxic nucleus pulpous (NP) surrounded by the more oxygenated annulus fibrosus (AF). Lactic acid, an abundant end-product of NP glycolysis, has long been viewed as a harmful waste that acidifies disc tissue and decreases cell viability and function. As lactic acid is readily converted into lactate in disc tissue, the objective of this study was to determine whether lactate could be used by AF cells as a carbon source rather than being removed from disc tissue as a waste byproduct. Methods Import and conversion of lactate to tricarboxylic acid (TCA) cycle intermediates and amino acids in rabbit AF cells were measured by heavy-isotope (13C-lactate) tracing experiments using mass spectrometry. Levels of protein expression of lactate converting enzymes, lactate importer and exporter in NP and AF tissues were quantified by Western blots. Effects of lactate on proteoglycan (35S-sulfate) and collagen (3H-proline) matrix protein synthesis and oxidative phosphorylation (Seahorse XFe96 Extracellular Flux Analyzer) in AF cells were assessed. Results Heavy-isotope tracing experiments revealed that AF cells imported and converted lactate into TCA cycle intermediates and amino acids using in vitro cell culture and in vivo models. Addition of exogenous lactate (4 mM) in culture media induced expression of the lactate importer MCT1 and increased oxygen consumption rate by 50%, mitochondrial ATP-linked respiration by 30%, and collagen synthesis by 50% in AF cell cultures grown under physiologic oxygen (2-5% O2) and glucose concentration (1-5 mM). AF tissue highly expresses MCT1, LDH-H, an enzyme that preferentially converts lactate to pyruvate, and PDH, an enzyme that converts pyruvate to acetyl-coA. In contrast, NP tissue highly expresses MCT4, a lactate exporter, and LDH-M, an enzyme that preferentially converts pyruvate to lactate. Conclusions These findings support disc lactate-dependent metabolic symbiosis in which lactate produced by the hypoxic, glycolytic NP cells is utilized by the more oxygenated AF cells via oxidative phosphorylation for energy and matrix production, thus shifting the current research paradigm of viewing disc lactate as a waste product to considering it as an important biofuel. These scientifically impactful results suggest novel therapeutic targets in disc metabolism and degeneration.

Abstract 241: Acetylomic and Metabolomic Alterations in Aged Hearts: Role for Silent Information Regulator (SIRT) 3

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Jimmy Zhang ◽  
William R Urciuoli ◽  
Paul S Brookes ◽  
George A Porter ◽  
Sergiy M Nadtochiy
Keyword(s):  
Metabolic Pathways ◽  
Carbon Flux ◽  
Tca Cycle ◽  
Adult Group ◽  
Protein Levels ◽  
Mitochondrial Alterations ◽  
Age Related ◽  
Transport Chain ◽  
Tca Cycle Intermediates ◽  
Substantial Decline

Introduction: SIRT3 is a mitochondrial metabolic regulator, and a decline in function of SIRT3 may play a role in age-related mitochondrial alterations. The aim of this study was to investigate the possible down-regulation of SIRT3 activity in aged hearts, and to identify which metabolic pathways in aged hearts may be impaired due to SIRT3 dysfunction. Methods: Mitochondria were isolated from WT adult (7 mo.), SIRT3 -/- adult (7 mo.) and WT aged (18 mo.) hearts. Acetylated proteins in mitochondrial samples were identified using 2D gels and mass spectrometry. Metabolite concentrations and carbon fluxes through core metabolic pathways were determined using 13 C-labeled substrates and LC-MS/MS. Results: Mitochondrial acetylation patterns in the SIRT3 -/- adult group matched those found in the WT aged group; the level of acetylation was significantly higher than in WT adult. While the SIRT3 -/- samples exhibited zero SIRT3 protein content, no difference in SIRT3 protein level was seen between adult and aged WT hearts. Mechanistically, this suggests that alterations in mitochondrial acetylation during aging were not caused by lower SIRT3 protein levels, but rather by a lower SIRT3 enzymatic activity. Furthermore, aged myocardium exhibited 40% lower NAD + levels, which may underlie compromised SIRT3 activity. ATP levels were decreased in both SIRT3 -/- and WT aged hearts, suggesting possible defects in energy metabolism. Using metabolomics, we demonstrated that alterations of TCA cycle intermediates were similar in SIRT3 -/- and WT aged hearts (relative to WT adult), and included a substantial decline of carbon flux through α-ketoglutarate and malate. Furthermore, regulation of energy production might also be impaired at the level of the electron transport chain, where Complex I was significantly inhibited in both SIRT3 deficient and aged hearts. Conclusions: Collectively these data suggested that acetylomic and metabolomic fingerprints observed in SIRT3 -/- hearts were recapitulated in aged hearts.

scholarly journals Ammonia inhibits energy metabolism in astrocytes in a rapid and glutamate dehydrogenase 2-dependent manner

2020 ◽  
Vol 13 (10) ◽  
pp. dmm047134
Author(s):  
Leonie Drews ◽  
Marcel Zimmermann ◽  
Philipp Westhoff ◽  
Dominik Brilhaus ◽  
Rebecca E. Poss ◽  
...  
Keyword(s):  
Amino Acids ◽  
Energy Metabolism ◽  
Glutamate Dehydrogenase ◽  
Mitochondrial Respiration ◽  
Tca Cycle ◽  
Dependent Manner ◽  
Independent Manner ◽  
The Tca Cycle ◽  
Branched Chain ◽  
Tca Cycle Intermediates

ABSTRACTAstrocyte dysfunction is a primary factor in hepatic encephalopathy (HE) impairing neuronal activity under hyperammonemia. In particular, the early events causing ammonia-induced toxicity to astrocytes are not well understood. Using established cellular HE models, we show that mitochondria rapidly undergo fragmentation in a reversible manner upon hyperammonemia. Further, in our analyses, within a timescale of minutes, mitochondrial respiration and glycolysis were hampered, which occurred in a pH-independent manner. Using metabolomics, an accumulation of glucose and numerous amino acids, including branched chain amino acids, was observed. Metabolomic tracking of 15N-labeled ammonia showed rapid incorporation of 15N into glutamate and glutamate-derived amino acids. Downregulating human GLUD2 [encoding mitochondrial glutamate dehydrogenase 2 (GDH2)], inhibiting GDH2 activity by SIRT4 overexpression, and supplementing cells with glutamate or glutamine alleviated ammonia-induced inhibition of mitochondrial respiration. Metabolomic tracking of 13C-glutamine showed that hyperammonemia can inhibit anaplerosis of tricarboxylic acid (TCA) cycle intermediates. Contrary to its classical anaplerotic role, we show that, under hyperammonemia, GDH2 catalyzes the removal of ammonia by reductive amination of α-ketoglutarate, which efficiently and rapidly inhibits the TCA cycle. Overall, we propose a critical GDH2-dependent mechanism in HE models that helps to remove ammonia, but also impairs energy metabolism in mitochondria rapidly.

IDENTIFYING CHEMICAL REACTION NETWORK MODELS

2007 ◽  
Vol 40 (5) ◽  
pp. 225-230 ◽  
Author(s):  
S.C. Burnham ◽  
M.J. Willis ◽  
A.R Wright
Keyword(s):  
Chemical Reaction ◽  
Reaction Network ◽  
Network Models ◽  
Chemical Reaction Network
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