Capturing Metabolite Channeling in Metabolic Flux Phenotypes

Williams, Thomas Christopher Rhys; Sweetlove, Lee J.; Ratcliffe, George

doi:10.1104/pp.111.184887

Cited by 41 publications

(37 citation statements)

References 19 publications

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“…The reverse situation, lack of IF in spite of a substrate conversion by reactions implying KIEs, is observed in the case of metabolite channeling ( [94], Figure 1). Here, the first and often all subsequent products are immediately and quantitatively transferred to the next enzyme, for example, within in a multi-enzyme complex [105], excluding an exchange of (bound) intermediates with (free) compounds in the cytoplasm.…”

Section: Kinetic Isotope Effects On Enzyme-catalysed Reactions and Pamentioning

confidence: 83%

“…These are then either enriched or depleted in the heavy isotope relative to the substrate, and the isotopic shifts are reciprocal to their yields (isotopic balance, for mathematical details see Tcherkez et al [95]). [94]. However, IF is observed, when the conversion of a substrate by a reaction implying a KIE is not quantitative.…”

Section: Kinetic Isotope Effects On Enzyme-catalysed Reactions and Pamentioning

confidence: 88%

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Multi-factorialin vivostable isotope fractionation: causes, correlations, consequences and applications

Schmidt

Robins

Werner

2015

Isotopes in Environmental and Health Studies

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Many physical and chemical processes in living systems are accompanied by isotope fractionation on H, C, N, O and S. Although kinetic or thermodynamic isotope effects are always the basis, their in vivo manifestation is often modulated by secondary influences. These include metabolic branching events or metabolite channeling, metabolite pool sizes, reaction mechanisms, anatomical properties and compartmentation of plants and animals, and climatological or environmental conditions. In the present contribution, the fundamentals of isotope effects and their manifestation under in vivo conditions are outlined. The knowledge about and the understanding of these interferences provide a potent tool for the reconstruction of physiological events in plants and animals, their geographical origin, the history of bulk biomass and the biosynthesis of defined representatives. It allows the use of isotope characteristics of biomass for the elucidation of biochemical pathways and reaction mechanisms and for the reconstruction of climatic, physiological, ecological and environmental conditions during biosynthesis. Thus, it can be used for the origin and authenticity control of food, the study of ecosystems and animal physiology, the reconstruction of present and prehistoric nutrition chains and paleaoclimatological conditions. This is demonstrated by the outline of fundamental and application-orientated examples for all bio-elements. The aim of the review is to inform (advanced) students from various disciplines about the whole potential and the scope of stable isotope characteristics and fractionations and to provide them with a comprehensive introduction to the literature on fundamental aspects and applications.

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Section: Kinetic Isotope Effects On Enzyme-catalysed Reactions and Pamentioning

confidence: 83%

Section: Kinetic Isotope Effects On Enzyme-catalysed Reactions and Pamentioning

confidence: 88%

Multi-factorialin vivostable isotope fractionation: causes, correlations, consequences and applications

Schmidt

Robins

Werner

2015

Isotopes in Environmental and Health Studies

View full text Add to dashboard Cite

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“…Furthermore, theoretical frameworks for using labelling data to establish or refute metabolic channelling have recently been put forward (Williams et al . ) and could equally be applied to photorespiration. A simpler approach, however, may be to introduce enzymes that compete for substrate with those of the photorespiratory pathway in order to ascertain if these pools are spatially separate from one another.…”

Section: Current Understanding Of the Photorespiratory Pathwaymentioning

confidence: 99%

Perspectives on plant photorespiratory metabolism

et al. 2012

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Being intimately intertwined with (C3) photosynthesis, photorespiration is an incredibly high flux-bearing pathway. Traditionally, the photorespiratory cycle was viewed as closed pathway to refill the Calvin-Benson cycle with organic carbon. However, given the network nature of metabolism, it hence follows that photorespiration will interact with many other pathways. In this article, we review current understanding of these interactions and attempt to define key priorities for future research, which will allow us greater fundamental comprehension of general metabolic and developmental consequences of perturbation of this crucial metabolic process.

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“…Such constraints may be related to the existence of macromolecular complexes associating enzymes belonging to the same metabolic pathway. These so-called metabolons (59) were described for glycolytic enzymes in several organisms ranging from plants (60,61), to human (62,63) and yeast (64). Metabolon allows passing (channeling) the intermediary metabolites from one enzyme to the consecutive one within a given metabolic pathway, forming a metabolite tunnel.…”

Section: Discussionmentioning

confidence: 99%

Linking Post-Translational Modifications and Variation of Phenotypic Traits

Albertin

Marullo

Bely

et al. 2013

Molecular & Cellular Proteomics

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Enzymes can be post-translationally modified, leading to isoforms with different properties. The phenotypic consequences of the quantitative variability of isoforms have never been studied. We used quantitative proteomics to dissect the relationships between the abundances of the enzymes and isoforms of alcoholic fermentation, metabolic traits, and growth-related traits in Saccharomyces cerevisiae. Although the enzymatic pool allocated to the fermentation proteome was constant over the culture media and the strains considered, there was variation in abundance of individual enzymes and sometimes much more of their isoforms, which suggests the existence of selective constraints on total protein abundance and trade-offs between isoforms. Variations in abundance of some isoforms were significantly associated to metabolic traits and growth-related traits. In particular, cell size and maximum population size were highly correlated to the degree of N-terminal acetylation of the alcohol dehydrogenase. The fermentation proteome was found to be shaped by human selection, through the differential targeting of a few isoforms for each food-processing origin of strains. These results highlight the importance of posttranslational modifications in the diversity of metabolic and life-history traits. Molecular & Cellular Proteomics 12: 10.1074/mcp.M112.024349, 720 -735, 2013.The key problem in understanding genotype-phenotype relationships is the complexity arising from multiple levels of cellular functioning. Among them, metabolic networks involve series of interconnected chemical reactions catalyzed by enzymes, allowing the transformation of input substrates into intermediate or final metabolites. These networks play an essential role in an organism's growth, reproduction, and ability to maintain cell integrity and to respond to environmental changes (1, 2). The metabolic fluxes, as well as the metabolite concentrations, are governed by the activity of the enzymes, which depends on three types of factors: kinetic parameters, enzyme abundance, and activation state of the enzyme. The kinetic parameters are determined by the sequence and the three-dimensional structure of the protein (3). The abundance of the enzymes is the result of numerous molecular processes taking place from the transcriptional to the translational level, including epigenetic modifications of the DNA and chromatin (4), transcriptional regulation by transcription factors (5), mRNA capping and splicing and small RNA regulation (6), protein turnover (7), etc. The enzyme activation state is primarily because of post-translational modifications of the native protein, themselves highly regulated (8, 9). Other mechanisms involved in enzyme activity are proteinprotein interactions and allosteric regulation, such mechanisms being sometimes mediated through post-translational modifications (10, 11). The resulting isoforms can display differences in activity, affinity for partners (protein or effectors), and stability (12). The most studied modification is the reversibl...

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Capturing Metabolite Channeling in Metabolic Flux Phenotypes

Cited by 41 publications

References 19 publications

Multi-factorialin vivostable isotope fractionation: causes, correlations, consequences and applications

Multi-factorialin vivostable isotope fractionation: causes, correlations, consequences and applications

Perspectives on plant photorespiratory metabolism

Linking Post-Translational Modifications and Variation of Phenotypic Traits

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