Branched-chain Amino Acid Metabolon

Islam, Mohammad Mainul; Nautiyal, Manisha; Wynn, R. Max; Mobley, James A.; Chuang, David T.; Hutson, Susan M.

doi:10.1074/jbc.m109.048777

Cited by 85 publications

(37 citation statements)

References 59 publications

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“…Therefore, substantial catabolism of consumed N sources, which first involves transaminations (16,17,49), occurred inside the cells and was accompanied by substantial de novo synthesis of proteinogenic amino acids. Such a dual allocation of the consumed amino acids was made possible by the similar orders of magnitude of the catalytic efficiencies of aminoacyl-tRNA synthetases and transaminases (50)(51)(52)(53). The question arises why S. cerevisiae breaks down a large portion of the consumed amino acids and, thereafter, resynthesizes amino acids to fulfill anabolic requirements.…”

Section: Discussionmentioning

confidence: 99%

Management of Multiple Nitrogen Sources during Wine Fermentation by Saccharomyces cerevisiae

Crépin

Truong

Bloem

et al. 2017

Appl Environ Microbiol

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During fermentative growth in natural and industrial environments, Saccharomyces cerevisiae must redistribute the available nitrogen from multiple exogenous sources to amino acids in order to suitably fulfill anabolic requirements. To exhaustively explore the management of this complex resource, we developed an advanced strategy based on the reconciliation of data from a set of stable isotope tracer experiments with labeled nitrogen sources. Thus, quantifying the partitioning of the N compounds through the metabolism network during fermentation, we demonstrated that, contrary to the generally accepted view, only a limited fraction of most of the consumed amino acids is directly incorporated into proteins. Moreover, substantial catabolism of these molecules allows for efficient redistribution of nitrogen, supporting the operative de novo synthesis of proteinogenic amino acids. In contrast, catabolism of consumed amino acids plays a minor role in the formation of volatile compounds. Another important feature is that the ␣-keto acid precursors required for the de novo syntheses originate mainly from the catabolism of sugars, with a limited contribution from the anabolism of consumed amino acids. This work provides a comprehensive view of the intracellular fate of consumed nitrogen sources and the metabolic origin of proteinogenic amino acids, highlighting a strategy of distribution of metabolic fluxes implemented by yeast as a means of adapting to environments with changing and scarce nitrogen resources. IMPORTANCE A current challenge for the wine industry, in view of the extensive competition in the worldwide market, is to meet consumer expectations regarding the sensory profile of the product while ensuring an efficient fermentation process. Understanding the intracellular fate of the nitrogen sources available in grape juice is essential to the achievement of these objectives, since nitrogen utilization affects both the fermentative activity of yeasts and the formation of flavor compounds. However, little is known about how the metabolism operates when nitrogen is provided as a composite mixture, as in grape must. Here we quantitatively describe the distribution through the yeast metabolic network of the N moieties and C backbones of these nitrogen sources. Knowledge about the management of a complex resource, which is devoted to improvement of the use of the scarce N nutrient for growth, will be useful for better control of the fermentation process and the sensory quality of wines.KEYWORDS complex nitrogen resource, metabolic network, metabolism, nitrogen, quantitative analysis, regulation, yeasts T he management of nutrients provided by the external environment, mainly carbon and nitrogen, and their redistribution inside the cells for the formation of biosynthetic precursors through the metabolic network are essential for all living organisms. The topology of the metabolic network of the yeast Saccharomyces cerevisiae is one of

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Section: Discussionmentioning

confidence: 99%

Management of Multiple Nitrogen Sources during Wine Fermentation by Saccharomyces cerevisiae

Crépin

Truong

Bloem

et al. 2017

Appl Environ Microbiol

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“…Since reductive amination can only occur when the ammonia concentration approaches the K m value for ammonia, it is likely that enzymatic complexes between GDH and the respective aminotransferases must exist to facilitate this reaction in vivo and there is some experimental evidence to suggest that this is indeed the case (Fahien et al 1977, Islam et al 2010, McKenna 2011). …”

Section: Enzymatic Reactions Involving Glutamate As Substrate or Productmentioning

confidence: 99%

Glutamate Metabolism in the Brain Focusing on Astrocytes

Schousboe

Scafidi

Bak

et al. 2014

Advances in Neurobiology

301

217

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Metabolism of glutamate, the main excitatory neurotransmitter and precursor of GABA, is exceedingly complex and highly compartmentalized in brain. Maintenance of these neurotransmitter pools is strictly dependent on the de novo synthesis of glutamine in astrocytes which requires both the anaplerotic enzyme pyruvate carboxylase and glutamine synthetase. Glutamate is formed directly from glutamine by deamidation via phosphate activated glutaminase a reaction that also yields ammonia. Glutamate plays key roles linking carbohydrate and amino acid metabolism via the tricarboxylic acid (TCA) cycle, as well as in nitrogen trafficking and ammonia homeostasis in brain. The anatomical specialization of astrocytic endfeet enables these cells to rapidly and efficiently remove neurotransmitters from the synaptic cleft to maintain homeostasis, and to provide glutamine to replenish neurotransmitter pools in both glutamatergic and GABAergic neurons. Since the glutamate-glutamine cycle is an open cycle that actively interfaces with other pathways, the de novo synthesis of glutamine in astrocytes helps to maintain the operation of this cycle. The fine-tuned biochemical specialization of astrocytes allows these cells to respond to subtle changes in neurotransmission by dynamically adjusting their anaplerotic and glycolytic activities, and adjusting the amount of glutamate oxidized for energy relative to direct formation of glutamine, to meet the demands for maintaining neurotransmission. This chapter summarizes the evidence that astrocytes are essential and dynamic partners in both glutamatergic and GABAergic neurotransmission in brain.

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“…As the thermodynamic equilibrium of the GDH-catalyzed reaction and the high K m value for [

{normalNH}_{normal4}^{normal+}

of GDH counteract such amination (75)] it has been proposed that the intra-mitochondrial milieu possibly coupled to a metabolomic complex between PAG, GDH, and the transaminases in question, i.e., ALAT and BCAA-aminotransferase may facilitate the reactions (11). Actually, a metabolomic coupling between GDH and ALAT as well as BCAA-aminotransferase has been experimentally demonstrated (76, 77). …”

Section: Contentmentioning

confidence: 99%

Astrocytic Control of Biosynthesis and Turnover of the Neurotransmitters Glutamate and GABA

Schousboe¹,

Bak²,

2013

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Glutamate and GABA are the quantitatively major neurotransmitters in the brain mediating excitatory and inhibitory signaling, respectively. These amino acids are metabolically interrelated and at the same time they are tightly coupled to the intermediary metabolism including energy homeostasis. Astrocytes play a pivotal role in the maintenance of the neurotransmitter pools of glutamate and GABA since only these cells express pyruvate carboxylase, the enzyme required for de novo synthesis of the two amino acids. Such de novo synthesis is obligatory to compensate for catabolism of glutamate and GABA related to oxidative metabolism when the amino acids are used as energy substrates. This, in turn, is influenced by the extent to which the cycling of the amino acids between neurons and astrocytes may occur. This cycling is brought about by the glutamate/GABA – glutamine cycle the operation of which involves the enzymes glutamine synthetase (GS) and phosphate-activated glutaminase together with the plasma membrane transporters for glutamate, GABA, and glutamine. The distribution of these proteins between neurons and astrocytes determines the efficacy of the cycle and it is of particular importance that GS is exclusively expressed in astrocytes. It should be kept in mind that the operation of the cycle is associated with movement of ammonia nitrogen between the two cell types and different mechanisms which can mediate this have been proposed. This review is intended to delineate the above mentioned processes and to discuss quantitatively their relative importance in the homeostatic mechanisms responsible for the maintenance of optimal conditions for the respective neurotransmission processes to operate.

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Branched-chain Amino Acid Metabolon

Cited by 85 publications

References 59 publications

Management of Multiple Nitrogen Sources during Wine Fermentation by Saccharomyces cerevisiae

Management of Multiple Nitrogen Sources during Wine Fermentation by Saccharomyces cerevisiae

Glutamate Metabolism in the Brain Focusing on Astrocytes

Astrocytic Control of Biosynthesis and Turnover of the Neurotransmitters Glutamate and GABA

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