A pathway map of glutamate metabolism

Abstract

Glutamate metabolism plays a vital role in biosynthesis of nucleic acids and proteins. It is also associated with a number of different stress responses. Deficiency of enzymes involved in glutamate metabolism is associated with various disorders including gyrate atrophy, hyperammonemia, hemolytic anemia, γ-hydoxybutyric aciduria and 5-oxoprolinuria. Here, we present a pathway map of glutamate metabolism representing metabolic intermediates in the pathway, 107 regulator molecules, 9 interactors and 3 types of post-translational modifications. This pathway map provides detailed information about enzyme regulation, protein-enzyme interactions, post-translational modifications of enzymes and disorders due to enzyme deficiency. The information included in the map was based on published experimental evidence reported from mammalian systems.

From Krebs to clinic: glutamine metabolism to cancer therapy

“…Glutamine itself can contribute to nucleotide biosynthesis and uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis for support of protein folding and trafficking 210 , or is converted to glutamate by glutaminase (GLS or GLS2) 28 . Glutamate can contribute to the synthesis of glutathione 110 , and has many other metabolic fates in the cell that impact on several inborn errors of metabolism, which were recently reviewed 211 . Glutamate is converted to α-ketoglutarate (αKG) through one of two sets of enzymes, glutamate dehydrogenase (GLUD1 or GLUD2, henceforth referred to collectively as GLUD) or aminotransferases 30 .…”

Erratum: From Krebs to clinic: glutamine metabolism to cancer therapy

“…Glutamate can contribute to the synthesis of glutathione 110 , and has many other metabolic fates in the cell that impact on several inborn errors of metabolism, which were recently reviewed 211 . Glutamate is converted to α-ketoglutarate (αKG) through one of two sets of enzymes, glutamate dehydrogenase (GLUD1 or GLUD2, henceforth referred to collectively as GLUD) or aminotransferases 30 .…”

Inborn errors of enzymes in glutamate metabolism

“…It is involved in amino acid synthesis and catabolism and as such involved in many metabolic pathways. Glutamate is directly metabolised by approximately 25 enzymes . Together with glutamine, glutamate plays an important role in ammonia detoxification by capturing ammonia—forming glutamine—and providing the urea cycle with intermediates .…”

“…Glutamate is directly metabolised by approximately 25 enzymes. 1 Together with glutamine, glutamate plays an important role in ammonia detoxification by capturing ammonia-forming glutamine-and providing the urea cycle with intermediates. 5 Glutamine is needed for NAD + production, an important metabolite for redox reactions and is also incorporated into proteins, and a source of purines and pyrimidines.…”

“…The amino acids glutamate and glutamine are key players in metabolism, functioning as both substrate and product in various enzymatic reactions. 1 Glutamate is the main excitatory neurotransmitter in the central nervous system and triggers responses implicated in neuronal migration and differentiation, synapse remodelling and axon myelination. 2,3 Additionally, glutamate is the precursor of glutathione and the tricarboxylic acid (TCA) cycle intermediates and therefore plays a role in redox state and energy metabolism respectively.…”