Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signalin...Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.展开更多
According to Descartes,minds and bodies are distinct kinds of “substance”,and they cannot have causal interactions.However,in neuroscience,the two-way interaction between the brain and peripheral organs is an emergi...According to Descartes,minds and bodies are distinct kinds of “substance”,and they cannot have causal interactions.However,in neuroscience,the two-way interaction between the brain and peripheral organs is an emerging field of research.Several lines of evidence highlight the importance of such interactions.For example,the peripheral metabolic systems are overwhelmingly regulated by the mind(brain),and anxiety and depression greatly affect the functioning of these systems.Also,psychological stress can cause a variety of physical symptoms,such as bone loss.Moreover,the gut microbiota appears to play a key role in neuropsychiatric and neurodegenerative diseases.Mechanistically,as the command center of the body,the brain can regulate our internal organs and glands through the autonomic nervous system and neuroendocrine system,although it is generally considered to be outside the realm of voluntary control.The autonomic nervous system itself can be further subdivided into the sympathetic and parasympathetic systems.The sympathetic division functions a bit like the accelerator pedal on a car,and the parasympathetic division functions as the brake.The high center of the autonomic nervous system and the neuroendocrine system is the hypothalamus,which contains several subnuclei that control several basic physiological functions,such as the digestion of food and regulation of body temperature.Also,numerous peripheral signals contribute to the regulation of brain functions.Gastrointestinal(GI) hormones,insulin,and leptin are transported into the brain,where they regulate innate behaviors such as feeding,and they are also involved in emotional and cognitive functions.The brain can recognize peripheral inflammatory cytokines and induce a transient syndrome called sick behavior(SB),characterized by fatigue,reduced physical and social activity,and cognitive impairment.In summary,knowledge of the biological basis of the interactions between the central nervous system and peripheral organs will promote the full understanding 展开更多
Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity,damaging the neurons.However,how lipids are metabolized by spinal cord neurons after spinal cord injury ...Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity,damaging the neurons.However,how lipids are metabolized by spinal cord neurons after spinal cord injury remains unclear.Herein,we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord injury.We found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in mice.Lipid droplet accumulation could be induced by myelin debris in HT22 cells.Myelin debris degradation by phospholipase led to massive free fatty acid production,which increased lipid droplet synthesis,β-oxidation,and oxidative phosphorylation.Excessive oxidative phosphorylation increased reactive oxygen species generation,which led to increased lipid peroxidation and HT22 cell apoptosis.Bromocriptine was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway,thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 cells.Motor function,lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord injury.The results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.展开更多
Acidithiobacillus caldus is one of the dominant sulfur-oxidizing bacteria in bioleaching reactors. It plays the essential role in maintaining the high acidity and oxidation of reduced inorganic sulfur compounds during...Acidithiobacillus caldus is one of the dominant sulfur-oxidizing bacteria in bioleaching reactors. It plays the essential role in maintaining the high acidity and oxidation of reduced inorganic sulfur compounds during bioleaching process. In this report, the complete genome sequence of A. caldus SM-1 is presented. The genome is composed of one chromosome （2,932,225 bp） and four plasmids （pLAtcl, pLAtc2, pLAtc3, pLAtcm） and it is rich in repetitive sequences （accounting for 11% of the total genome）, which are often associated with transposable genetic elements. In particular, twelve copies of ISAtfe and thirty-seven copies of ISAtcl have been identified, suggesting that they are active transposons in the genome. A. caldus SM-1 encodes all enzymes for the central metabolism and the assimilation of carbon compounds, among which 29 proteins/enzymes were identifiable with proteomic tools. The SM-1 fixes CO2 via the classical Calvin-Bassham--Benson （CBB） cycle, and can operate complete Embden-Meyerhof pathway （EMP）, pentose phosphate pathway （PPP）, and gluconeogenesis. It has an incomplete tricarboxylic acid cycle （TCA）. Four putative transporters involved in carbohydrate uptake were identified. Taken together, the results suggested that SM-1 was able to assimilate carbohydrates and this was subsequently confirmed experimentally because addition of 1% glucose or sucrose in basic salt medium significantly increased the growth of SM-1. It was concluded that the complete genome of SM-1 provided fundamental data for further investigation of its physiology and genetics, in addition to the carbon metabolism revealed in this study.展开更多
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
Metabolism is a fundamental process by which biochemicals are broken down to produce energy(catabolism) or used to build macromolecules(anabolism). Metabolism has received renewed attention as a mechanism that generat...Metabolism is a fundamental process by which biochemicals are broken down to produce energy(catabolism) or used to build macromolecules(anabolism). Metabolism has received renewed attention as a mechanism that generates molecules that modulate multiple cellular responses. This was first identified in cancer cells as the Warburg effect, but it is also present in immunocompetent cells. Studies have revealed a bidirectional influence of cellular metabolism and immune cell function, highlighting the significance of metabolic reprogramming in immune cell activation and effector functions. Metabolic processes such as glycolysis, oxidative phosphorylation, and fatty acid oxidation have been shown to undergo dynamic changes during immune cell response, facilitating the energetic and biosynthetic demands. This review aims to provide a better understanding of the metabolic reprogramming that occurs in different immune cells upon activation, with a special focus on central nervous system disorders. Understanding the metabolic changes of the immune response not only provides insights into the fundamental mechanisms that regulate immune cell function but also opens new approaches for therapeutic strategies aimed at manipulating the immune system.展开更多
Axonal regeneration in the central nervous system is an energy-intensive process.In contrast to mammals,adult zebrafish can functionally recover from neuronal injury.This raises the question of how zebrafish can cope ...Axonal regeneration in the central nervous system is an energy-intensive process.In contrast to mammals,adult zebrafish can functionally recover from neuronal injury.This raises the question of how zebrafish can cope with this high energy demand.We previously showed that in adult zebrafish,subjected to an optic nerve crush,an antagonistic axon-dendrite interplay exists wherein the retraction of retinal ganglion cell dendrites is a prerequisite for effective axonal repair.We postulate a‘dendrites for regeneration’paradigm that might be linked to intraneuronal mitochondrial reshuffling,as ganglion cells likely have insufficient resources to maintain dendrites and restore axons simultaneously.Here,we characterized both mitochondrial distribution and mitochondrial dynamics within the different ganglion cell compartments(dendrites,somas,and axons)during the regenerative process.Optic nerve crush resulted in a reduction of mitochondria in the dendrites during dendritic retraction,whereafter enlarged mitochondria appeared in the optic nerve/tract during axonal regrowth.Upon dendritic regrowth in the retina,mitochondrial density inside the retinal dendrites returned to baseline levels.Moreover,a transient increase in mitochondrial fission and biogenesis was observed in retinal ganglion cell somas after optic nerve damage.Taken together,these findings suggest that during optic nerve injury-induced regeneration,mitochondria shift from the dendrites to the axons and back again and that temporary changes in mitochondrial dynamics support axonal and dendritic regrowth after optic nerve crush.展开更多
Although a considerable increase in our knowledge concerning the importance of metabolic adjustments to unfavorable growth conditions has been recently provided, relatively little is known about the adjustments which ...Although a considerable increase in our knowledge concerning the importance of metabolic adjustments to unfavorable growth conditions has been recently provided, relatively little is known about the adjustments which occur in response to fluctuation in environmental factors. Evaluating the metabolic adjustments occurring under changing environmental conditions thus offers a good opportunity to increase our current understanding of the crosstalk between the major pathways which are affected by such conditions. To this end, plants growing under normal conditions were transferred to different light and temperature conditions which were anticipated to affect （amongst other processes） the rates of photosynthesis and photorespiration and characterized at the physiological, molecular, and metabolic levels following this transition. Our results revealed similar behavior in response to both treatments and imply a tight connec- tivity of photorespiration with the major pathways of plant metabolism. They further highlight that the majority of the regulation of these pathways is not mediated at the level of transcription but that leaf metabolism is rather pre-poised to adapt to changes in these input parameters.展开更多
The recent discovery of the Entner-Doudoroff(ED)pathway as a third glycolytic route beside Embden-Meyerhof-Parnas(EMP)and oxidative pentose phosphate(OPP)pathway in oxygenic photoautotrophs requires a revision of thei...The recent discovery of the Entner-Doudoroff(ED)pathway as a third glycolytic route beside Embden-Meyerhof-Parnas(EMP)and oxidative pentose phosphate(OPP)pathway in oxygenic photoautotrophs requires a revision of their central carbohydrate metabolism.In this study,unexpectedly,we observed that deletion of the ED pathway alone,and even more pronounced in combination with other glycolytic routes,diminished photoautotrophic growth in continuous light in the cyanobacterium Synechocystis sp.PCC 6803.Furthermore,we found that the ED pathway is required for optimal glycogen catabolism in parallel to an operating Calvin-Benson-Bassham(CBB)cycle.It is counter-intuitive that glycolytic routes,which are a reverse to the CBB cycle and do not provide any additional biosynthetic intermediates,are important under photoautotrophic conditions.However,observations on the ability to reactivate an arrested CBB cycle revealed that they form glycolytic shunts that tap the cellular carbohydrate reservoir to replenish the cycle.Taken together,our results suggest that the classical view of the CBB cycle as an autocatalytic,completely autonomous cycle that exclusively relies on its own enzymes and C02 fixation to regenerate ribulose-1,5-bisphosphate for Rubisco is an oversimplification.We propose that in common with other known autocatalytic cycles,the CBB cycle likewise relies on anaplerotic reactions to compensate for the depletion of intermediates,particularly in transition states and under fluctuating light conditions that are common in nature.展开更多
A scheme of investigating the intracellular metabolic fluxes in central metabolism of Saccharomyces cerevisiae based on isotope model and tracer experiment was developed. The metabolic model applied in this study incl...A scheme of investigating the intracellular metabolic fluxes in central metabolism of Saccharomyces cerevisiae based on isotope model and tracer experiment was developed. The metabolic model applied in this study includes the Embden-Meyerhof-Parnas pathway,the pentose phosphate pathway,the tricarboxylic acid cycle,CO2 anaplerotic reactions,ethanol and acetate formation,and pathways involved in amino acid synthesis. The approach of hybridized genetic algorithm combined with the sequential simplex technique was used to optimize a quadratic error function without the requirement of the information on the partial derivatives. The impact of some key pa-rameters on the algorithm was studied. This approach was proved to be rapid and numerically stable in the analysis of the central metabolism of S.cerevisiae.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82230042 and 81930029(to ZY),U2004201(to FG and RYP)the China Postdoctoral Science Foundation,No.2020M683748(to RYP)。
文摘Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.
基金supported by the National Natural Science Foundation of China (31822026,31822018,31770936,82072489,32122039)the National Key R&D Program of China (2017YFA0205903,2017YFA0505800,2021ZD020390)+2 种基金the Key Research Program of Frontier Sciences of Chinese Academy of Sciences (QYZDB-SSW-SMC056)Beijing Natural Science Foundation (5222010)the Tsinghua University(School of Medicine)-Xiamen Changgeng Hospital Co.Ltd.Joint Research Center for Anaphylactic Disease。
文摘According to Descartes,minds and bodies are distinct kinds of “substance”,and they cannot have causal interactions.However,in neuroscience,the two-way interaction between the brain and peripheral organs is an emerging field of research.Several lines of evidence highlight the importance of such interactions.For example,the peripheral metabolic systems are overwhelmingly regulated by the mind(brain),and anxiety and depression greatly affect the functioning of these systems.Also,psychological stress can cause a variety of physical symptoms,such as bone loss.Moreover,the gut microbiota appears to play a key role in neuropsychiatric and neurodegenerative diseases.Mechanistically,as the command center of the body,the brain can regulate our internal organs and glands through the autonomic nervous system and neuroendocrine system,although it is generally considered to be outside the realm of voluntary control.The autonomic nervous system itself can be further subdivided into the sympathetic and parasympathetic systems.The sympathetic division functions a bit like the accelerator pedal on a car,and the parasympathetic division functions as the brake.The high center of the autonomic nervous system and the neuroendocrine system is the hypothalamus,which contains several subnuclei that control several basic physiological functions,such as the digestion of food and regulation of body temperature.Also,numerous peripheral signals contribute to the regulation of brain functions.Gastrointestinal(GI) hormones,insulin,and leptin are transported into the brain,where they regulate innate behaviors such as feeding,and they are also involved in emotional and cognitive functions.The brain can recognize peripheral inflammatory cytokines and induce a transient syndrome called sick behavior(SB),characterized by fatigue,reduced physical and social activity,and cognitive impairment.In summary,knowledge of the biological basis of the interactions between the central nervous system and peripheral organs will promote the full understanding
基金supported by the National Natural Science Foundation of China,Nos.82071376(to ZC)and 82001471(to CJ)the Natural Science Foundation of Shanghai,No.20ZR1410500(to ZC).
文摘Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity,damaging the neurons.However,how lipids are metabolized by spinal cord neurons after spinal cord injury remains unclear.Herein,we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord injury.We found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in mice.Lipid droplet accumulation could be induced by myelin debris in HT22 cells.Myelin debris degradation by phospholipase led to massive free fatty acid production,which increased lipid droplet synthesis,β-oxidation,and oxidative phosphorylation.Excessive oxidative phosphorylation increased reactive oxygen species generation,which led to increased lipid peroxidation and HT22 cell apoptosis.Bromocriptine was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway,thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 cells.Motor function,lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord injury.The results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.
基金supported by the National Science Foundation of China(No.30870039)the National Basic Research Program of China(973 Program,No.2010CB630903)
文摘Acidithiobacillus caldus is one of the dominant sulfur-oxidizing bacteria in bioleaching reactors. It plays the essential role in maintaining the high acidity and oxidation of reduced inorganic sulfur compounds during bioleaching process. In this report, the complete genome sequence of A. caldus SM-1 is presented. The genome is composed of one chromosome （2,932,225 bp） and four plasmids （pLAtcl, pLAtc2, pLAtc3, pLAtcm） and it is rich in repetitive sequences （accounting for 11% of the total genome）, which are often associated with transposable genetic elements. In particular, twelve copies of ISAtfe and thirty-seven copies of ISAtcl have been identified, suggesting that they are active transposons in the genome. A. caldus SM-1 encodes all enzymes for the central metabolism and the assimilation of carbon compounds, among which 29 proteins/enzymes were identifiable with proteomic tools. The SM-1 fixes CO2 via the classical Calvin-Bassham--Benson （CBB） cycle, and can operate complete Embden-Meyerhof pathway （EMP）, pentose phosphate pathway （PPP）, and gluconeogenesis. It has an incomplete tricarboxylic acid cycle （TCA）. Four putative transporters involved in carbohydrate uptake were identified. Taken together, the results suggested that SM-1 was able to assimilate carbohydrates and this was subsequently confirmed experimentally because addition of 1% glucose or sucrose in basic salt medium significantly increased the growth of SM-1. It was concluded that the complete genome of SM-1 provided fundamental data for further investigation of its physiology and genetics, in addition to the carbon metabolism revealed in this study.
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
基金supported by NIH Grant Al-15614 (to CAD)the Ministerio de Ciencia e Innovacion (PID2020-120267BRI00AEI/10.13039/501100011033)(to RLV)。
文摘Metabolism is a fundamental process by which biochemicals are broken down to produce energy(catabolism) or used to build macromolecules(anabolism). Metabolism has received renewed attention as a mechanism that generates molecules that modulate multiple cellular responses. This was first identified in cancer cells as the Warburg effect, but it is also present in immunocompetent cells. Studies have revealed a bidirectional influence of cellular metabolism and immune cell function, highlighting the significance of metabolic reprogramming in immune cell activation and effector functions. Metabolic processes such as glycolysis, oxidative phosphorylation, and fatty acid oxidation have been shown to undergo dynamic changes during immune cell response, facilitating the energetic and biosynthetic demands. This review aims to provide a better understanding of the metabolic reprogramming that occurs in different immune cells upon activation, with a special focus on central nervous system disorders. Understanding the metabolic changes of the immune response not only provides insights into the fundamental mechanisms that regulate immune cell function but also opens new approaches for therapeutic strategies aimed at manipulating the immune system.
基金financially supported by the Katholieke Universiteit Leuven Research Council (C14/18/053)the research foundation Flanders (FWO) (G082221N)+1 种基金a personal L’Oréal/UNESCO (For Women in Science) fellowshipa personal FWO fellowship
文摘Axonal regeneration in the central nervous system is an energy-intensive process.In contrast to mammals,adult zebrafish can functionally recover from neuronal injury.This raises the question of how zebrafish can cope with this high energy demand.We previously showed that in adult zebrafish,subjected to an optic nerve crush,an antagonistic axon-dendrite interplay exists wherein the retraction of retinal ganglion cell dendrites is a prerequisite for effective axonal repair.We postulate a‘dendrites for regeneration’paradigm that might be linked to intraneuronal mitochondrial reshuffling,as ganglion cells likely have insufficient resources to maintain dendrites and restore axons simultaneously.Here,we characterized both mitochondrial distribution and mitochondrial dynamics within the different ganglion cell compartments(dendrites,somas,and axons)during the regenerative process.Optic nerve crush resulted in a reduction of mitochondria in the dendrites during dendritic retraction,whereafter enlarged mitochondria appeared in the optic nerve/tract during axonal regrowth.Upon dendritic regrowth in the retina,mitochondrial density inside the retinal dendrites returned to baseline levels.Moreover,a transient increase in mitochondrial fission and biogenesis was observed in retinal ganglion cell somas after optic nerve damage.Taken together,these findings suggest that during optic nerve injury-induced regeneration,mitochondria shift from the dendrites to the axons and back again and that temporary changes in mitochondrial dynamics support axonal and dendritic regrowth after optic nerve crush.
文摘Although a considerable increase in our knowledge concerning the importance of metabolic adjustments to unfavorable growth conditions has been recently provided, relatively little is known about the adjustments which occur in response to fluctuation in environmental factors. Evaluating the metabolic adjustments occurring under changing environmental conditions thus offers a good opportunity to increase our current understanding of the crosstalk between the major pathways which are affected by such conditions. To this end, plants growing under normal conditions were transferred to different light and temperature conditions which were anticipated to affect （amongst other processes） the rates of photosynthesis and photorespiration and characterized at the physiological, molecular, and metabolic levels following this transition. Our results revealed similar behavior in response to both treatments and imply a tight connec- tivity of photorespiration with the major pathways of plant metabolism. They further highlight that the majority of the regulation of these pathways is not mediated at the level of transcription but that leaf metabolism is rather pre-poised to adapt to changes in these input parameters.
基金financed by grants from the Deutsche Forschungsgemeinschaft(GU1522/1-1,GU1522/2-1,WI1796/3-1,and FOR 2816)the Bundesministerium fur Bildung und Forschung(FP309).
文摘The recent discovery of the Entner-Doudoroff(ED)pathway as a third glycolytic route beside Embden-Meyerhof-Parnas(EMP)and oxidative pentose phosphate(OPP)pathway in oxygenic photoautotrophs requires a revision of their central carbohydrate metabolism.In this study,unexpectedly,we observed that deletion of the ED pathway alone,and even more pronounced in combination with other glycolytic routes,diminished photoautotrophic growth in continuous light in the cyanobacterium Synechocystis sp.PCC 6803.Furthermore,we found that the ED pathway is required for optimal glycogen catabolism in parallel to an operating Calvin-Benson-Bassham(CBB)cycle.It is counter-intuitive that glycolytic routes,which are a reverse to the CBB cycle and do not provide any additional biosynthetic intermediates,are important under photoautotrophic conditions.However,observations on the ability to reactivate an arrested CBB cycle revealed that they form glycolytic shunts that tap the cellular carbohydrate reservoir to replenish the cycle.Taken together,our results suggest that the classical view of the CBB cycle as an autocatalytic,completely autonomous cycle that exclusively relies on its own enzymes and C02 fixation to regenerate ribulose-1,5-bisphosphate for Rubisco is an oversimplification.We propose that in common with other known autocatalytic cycles,the CBB cycle likewise relies on anaplerotic reactions to compensate for the depletion of intermediates,particularly in transition states and under fluctuating light conditions that are common in nature.
基金Supported by the National Natural Science Foundation of China (No.20276065)the Special Funds for Major State BasicResearch Program of China (973 Program, 2007CB707805).
文摘A scheme of investigating the intracellular metabolic fluxes in central metabolism of Saccharomyces cerevisiae based on isotope model and tracer experiment was developed. The metabolic model applied in this study includes the Embden-Meyerhof-Parnas pathway,the pentose phosphate pathway,the tricarboxylic acid cycle,CO2 anaplerotic reactions,ethanol and acetate formation,and pathways involved in amino acid synthesis. The approach of hybridized genetic algorithm combined with the sequential simplex technique was used to optimize a quadratic error function without the requirement of the information on the partial derivatives. The impact of some key pa-rameters on the algorithm was studied. This approach was proved to be rapid and numerically stable in the analysis of the central metabolism of S.cerevisiae.
