Dr. Dariush Ghulami presented on glutamate production and ionotropic glutamate receptors. Some key points:
- Glutamate is the main excitatory neurotransmitter in the central nervous system, acting on ionotropic glutamate receptors.
- It is commercially produced primarily through fermentation and used in food/feed additives and pharmaceuticals.
- Ionotropic glutamate receptors are ligand-gated ion channels that include NMDA, AMPA, and kainate receptors. The NMDA receptor requires binding of glutamate and glycine and is permeable to calcium.
- NMDA receptor activation plays a role in long-term potentiation involved in learning and memory
9. Global market amino acids, 2004 9
Global market amino acids, 2014
Food industry: 65%
Feed Additives: 30%
Pharmaceutical: 5%
10. Commercial production of MSG is the largest and biggest industries world over.
Commercial Production:
Glutamic acid > lysine > methionine > threonine > Aspartic acid
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11. Methods of Commercial Production of Amino
Acids
extraction from natural sources,
chemical synthesis,
fermentation,
enzymatic catalysis
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13. Glutamic Acid by Chemical Synthesis 13
Resolution of Racemic Glutamic Acid
14. Fermentation Methods
Have been developed only for the preparation of (S )-lysine and (S )-glutamic acid
The carbon sources for these syntheses are cane or beet molasses, or a starch
hydrolysate.
Ammonia is the source of nitrogen,
oxygen is provided by passing compressed air into the fermenting mixture.
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16. Important applications of glutamate
Amino acid fertilizer production
Reduce high blood pressure
Amino Acids in Cosmetology
Amino Acids and Environment
Amino Acid Supplements
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18. Glutamate
Neurotransmitter at 75-80% of CNS synapses
Synthesized within the brain from
Glucose (via KREBS cycle/α-ketoglutarate)
Glutamine (from glial cells)
Actions terminated by uptake through excitatory amino acid
transporters (EAATs) in neurons and astrocytes
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28. Properties of NMDA Receptor
Blocked at resting membrane potential (coincidence detector)
Requires glycine binding
Permeable to Ca++ as well as Na
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35. References:
1. Maria S., Elena K., and Herman W. 2005. D-Serine Is the Dominant Endogenous Coagonist for NMDA Receptor
Neurotoxicity in Organotypic Hippocampal Slices. The Journal of Neuroscience.
2. Wim V., Wim R. and James R. 2000. AMPA Receptor Calcium Permeability, GluR2 Expression, and Selective
Motoneuron Vulnerability. The Journal of Neuroscience.
3. Brian S. Meldrum. 2012. Glutamate as a Neurotransmitter in the Brain: Review of Physiology and Pathology. The
Journal of Neuroscience.
4. Stephen F., Lonnie P., Chris J., Frank S., Katie M., Kevin K., Kasper B., Hongjie Y., Scott J., and Ray D. 2010.
Glutamate Receptor Ion Channels: Structure, Regulation, and Function. Pharmacol. Rev.
5. Derek B. Ionotropic Glutamate Receptors & CNS Disorders. 2009. CNS Neurol Disord Drug Targets.
6. Christian L. and Robert C. 2012. NMDA Receptor -Dependent Long-Term Potentiation and Long-Term Depression
(LTP /LTD). Cold Spring Harb Perspect Biol.
7. Susumu T. 2010. Regulation of Ionotropic Glutamate Receptors by Their Auxiliary Subunits. Physiology.
8. Addison A. 2012. The Monosodium Glutamate Story: The Commercial Production of MSG and Other Amino Acids
9. http://web.stanford.edu/group/hopes/cgi-bin/wordpress/2011/06/about-glutamate-toxicity/
10. K. Huthmacher., Wolfgang Leuchtenberger., K. Drauz,. 2005. Biotechnological production of amino acids and
derivatives: current status and prospects, Appl Microbiol Biotechnol.
11. A. Burkovski, 2003. Ammonium assimilation and nitrogen control in Corynebacterium glutamicum and its
relatives: An example for new regulatory mechanisms in actinomycetes. FEMS Microbiol. Rev.
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