From prebiotic chemistry to cellular metabolism—The chemical evolution of metabolism before Darwinian natural selection

Meléndez-Hevia, Enrique; Montero-Gómez, Nancy; Montero, Francisco

doi:10.1016/j.jtbi.2007.11.012

Cited by 41 publications

(23 citation statements)

References 48 publications

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“…The overall network of interconnected reaction sequences that interconvert cellular metabolites constitutes cellular metabolism (Nelson and Cox 2005). Metabolism is adapted and optimized to achieve balance and economy (Meléndez-Hevia et al 2008). So, one of the attractors involved in biomolecular evolution is the minimizing of unwanted side reactions.…”

Section: Introductionmentioning

confidence: 99%

An evolutionary comparative scan for longevity-related oxidative stress resistance mechanisms in homeotherms

Pamplona

Barja

2011

Biogerontology

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Key mechanisms relating oxidative stress to longevity from an interespecies comparative approach are reviewed. Long-lived animal species show low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. Comparative physiology also shows that the specific compositional pattern of tissue macromolecules (proteins, lipids and nucleic acids) in long-lived animal species gives them an intrinsically high resistance to modification that likely contributes to their superior longevity. This is obtained in the case of lipids by decreasing the degree of fatty acid unsaturation, and in the case of proteins by lowering their methionine content. These findings are also substantiated from a phylogenomic approach. Nutritional or/and pharmacological interventions focused to modify some of these molecular traits were translated with modifications in animal longevity. It is proposed that natural selection tends to decrease the mitochondrial ROS generation and to increase the molecular resistance to the oxidative damage in long-lived species.

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Section: Introductionmentioning

confidence: 99%

An evolutionary comparative scan for longevity-related oxidative stress resistance mechanisms in homeotherms

Pamplona

Barja

2011

Biogerontology

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“…The same considerations must apply to the self-maintaining systems at the origin of life [6], [7]. Rosen [1] expressed this idea that catalysts must be produced by the system itself by saying that it must be closed to efficient causation .…”

Section: Introductionmentioning

confidence: 99%

A Simple Self-Maintaining Metabolic System: Robustness, Autocatalysis, Bistability

et al. 2010

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A living organism must not only organize itself from within; it must also maintain its organization in the face of changes in its environment and degradation of its components. We show here that a simple (M,R)-system consisting of three interlocking catalytic cycles, with every catalyst produced by the system itself, can both establish a non-trivial steady state and maintain this despite continuous loss of the catalysts by irreversible degradation. As long as at least one catalyst is present at a sufficient concentration in the initial state, the others can be produced and maintained. The system shows bistability, because if the amount of catalyst in the initial state is insufficient to reach the non-trivial steady state the system collapses to a trivial steady state in which all fluxes are zero. It is also robust, because if one catalyst is catastrophically lost when the system is in steady state it can recreate the same state. There are three elementary flux modes, but none of them is an enzyme-maintaining mode, the entire network being necessary to maintain the two catalysts.

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“…This phenomenon is known as the Warburg effect. This glycolytic phenotype is an apparently inefficient means of energy production as glycolysis generates two molecules of ATP and two of lactic acid from each molecule of glucose consumed, while oxidative phosphorylation (oxphos, for short) generates about 30 molecules of ATP from 1 molecule of glucose (8). Such a wasteful form of metabolism for generating ATP seems paradoxical.…”

Section: Disease Model: Human Multiple Myeloma (Mm)mentioning

confidence: 99%

“…It is reasonable to assume that the evolutionary process, which leads to this result, originated from the necessity to adjust the metabolic demand of cells according to the available energy sources and new functions. One might speculate that ADO straddled the two roles of information and energy source as a regulatory mechanism in primitive organisms (8). …”

Section: Introductionmentioning

confidence: 99%

Roles and Modalities of Ectonucleotidases in Remodeling the Multiple Myeloma Niche

et al. 2017

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Ectoenzymes are cell surface molecules, which represent functional bridges between the environment and the cytoplasm. One set of ectoenzymes—CD39, CD38, CD203a, and CD73—leads to the generation of adenosine (ADO) by metabolizing ATP and NAD+. While ADO is known to control inflammation and suppress immune responses, other aspects of ADO function are still obscure, mainly due to its short half-life in biological fluids. Human multiple myeloma (MM) grows in the closed system of the bone marrow (BM) niche representing an ideal setting for studying ectoenzymes and their products. Another source of information on ectoenzyme function may derive from in vivo results of anti-CD38 antibody therapy in MM. Current results, obtained from in vitro models and from preliminary in vivo findings, indicate that ectoenzymes produce ADO locally in the BM niche. Furthermore, MM cells release microvesicles (MV), which thanks to their molecular cargo and surface ectoenzymes may function as particulate communicators outside of the niche. During anti-CD38 antibody therapy, the MV carry therapeutic IgG, determining that the prevalent orientation of MV will be toward cells and tissues expressing receptors for the IgG Fc domain. The resulting picture is one where MM adopts an immune escape strategy based on reshaping the environmental niche. This adaptation is followed by actions of MV that are exerted in biological fluids and circulating immune cells. By coating FcRs+ cells, MV modify pericellular spaces, reproducing the metabolic halo generated by ectoenzymes within closed systems.

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From prebiotic chemistry to cellular metabolism—The chemical evolution of metabolism before Darwinian natural selection

Cited by 41 publications

References 48 publications

An evolutionary comparative scan for longevity-related oxidative stress resistance mechanisms in homeotherms

An evolutionary comparative scan for longevity-related oxidative stress resistance mechanisms in homeotherms

A Simple Self-Maintaining Metabolic System: Robustness, Autocatalysis, Bistability

Roles and Modalities of Ectonucleotidases in Remodeling the Multiple Myeloma Niche

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