Glutamate Metabolism


This pathway depicts the diverse metabolic fates and roles that glutamate plays in the body. As seen from this diagram, glutamate can serve as a precursor or substrate molecule for many compounds. For instance, glutamate can be generated from glutamine with the concomitant production of ammonia through the action of the enzyme glutaminase. Glutamate can also be oxidatively deaminated through glutamate dehydrogenase to produce 2-oxoglutarate and ammonia. Additionally, glutamate can be generated from alanine or aspartate in combination with 2-oxoglutarate using the enzyme transaminase. The resulting byproducts (pyruvate and oxaloacetate) are key components in glycolysis, gluconeogenesis and the TCA cycle. Glutamate and proline metabolism are also connected. In particular, 1-pyrroline-5-carboxylate is a biosynthetic metabolite that is synthesized from proline by the enzyme pyrroline-5-carboxylate reductase and converted into the amino acid glutamate by the enzyme 1-pyrroline-5-carboxylate dehydrogenase. Glutamate also plays an important role in the body’s disposal of excess nitrogen through the reaction catalyzed by glutamate dehydrogenase, which converts glutamate and NADP into 2-oxoglutarate, NADPH and ammonia. The ammonia is then excreted predominantly as urea. Glutamate can also participate with glutamine and ATP in the synthesis of several other phosphorylated compounds such as carbamoyl phosphate, phosphoribosylamine and glucosamine 6-phosphate. These molecules can serve as precursors for purine and polysaccharide metabolism. Another enzyme, glutamate-cysteine ligase (GCL), will conjugate glutamate and glycine with cysteine to produce glutathione, a key redox regulatory molecule in the cell. Glutamate also serves as the precursor for the synthesis of the neurotransmitter known as GABA (gamma-Aminobutyric acid) in GABA-ergic neurons. This reaction is catalyzed by glutamate decarboxylase (GAD), which is most abundant in the cerebellum and pancreas. Glutamate also serves as the most abundant fast excitatory neurotransmitter in the mammalian nervous system. At chemical synapses, glutamate is stored in vesicles. Nerve impulses trigger release of glutamate from the pre-synaptic cell. The glutamate then travels across the synapse, binding to glutamate sensitive receptors such as NMDA receptors on the post-synaptic cell, activating the cell.

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References

  1. Lehninger, A.L. (2005) Lehninger principles of biochemistry (4 th ed.). New York: W.H Freeman.
  2. Salway, J.G. (2004) Metabolism at a glance (3 rd ed.). Alden, Mass. : Blackwell Pub.