Methionine sulfoximine

Last updated
L-Methionine sulfoximine
L-Methionine sulfoximine.svg
Names
IUPAC name
(2S)-2-Amino-4-(S-methylsulfonimidoyl)butanoic acid
Other names
L-Methionine sulfoximine; MSO
Identifiers
3D model (JSmol)
1725509
ChEBI
ChemSpider
ECHA InfoCard 100.016.224 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 217-845-8
PubChem CID
UNII
  • InChI=1S/C5H12N2O3S/c1-11(7,10)3-2-4(6)5(8)9/h4,7H,2-3,6H2,1H3,(H,8,9)/t4-,11?/m0/s1
    Key: SXTAYKAGBXMACB-DPVSGNNYSA-N
  • CS(=N)(=O)CC[C@@H](C(=O)O)N
Properties
C5H12N2O3S
Molar mass 180.22 g·mol−1
Related compounds
Related compounds
 Buthionine sulfoximine
Glufosinate
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Methionine sulfoximine (MSO, also known as MetSox [1] ) is an irreversible glutamine synthetase inhibitor. It is the sulfoximine derivative of methionine with convulsant effects. [2]

L-Methionine sulfoximine is composed of two different diastereomers, which are L-S-Methionine sulfoximine and L-R-Methionine sulfoximine. These affect the longevity of the mouse model for Lou Gehrig's disease. [3] Overproduction of glutamate results to excitotoxicity, which kills the cell. Since methionine sulfoximine inhibits glutamate production in the brain, it prevents excitotoxicity. Thus, increasing the longevity of the mice. [4]

Mechanism of action

MSO is phosphorylated by glutamine synthetase. The resulting product acts as a transition state analog that is unable to diffuse from the active site, thereby inhibiting the enzyme. [5]

Phosphorylation of MSO by glutamine synthetase MSO Phosphorylation Mechanism.svg
Phosphorylation of MSO by glutamine synthetase

References

  1. ↑ Carroll, P.; Waddell, S. J.; Butcher, P. D.; Parish, T. (2011). "Methionine sulfoximine resistance in Mycobacterium tuberculosis is due to a single nucleotide deletion resulting in increased expression of the major glutamine synthetase, GlnA1". Microbial Drug Resistance. 17 (3): 351–355. doi:10.1089/mdr.2010.0125. PMC   3161625 . PMID   21875360.
  2. ↑ Rowe, WB; Meister, A (June 1970). "Identification of L-methionine-S-sulfoximine as the convulsant isomer of methionine sulfoximine". Proceedings of the National Academy of Sciences of the United States of America. 66 (2): 500–6. Bibcode:1970PNAS...66..500R. doi: 10.1073/pnas.66.2.500 . PMC   283073 . PMID   4393740.
  3. ↑ Brusilow, William S. A. (2017-04-24). "Identification of the isomer of methionine sulfoximine that extends the lifespan of the SOD1 G93A mouse". Neuroscience Letters. 647: 165–167. doi:10.1016/j.neulet.2017.03.029. ISSN   0304-3940. PMID   28323087. S2CID   45664203.
  4. ↑ Bame, Monica; Pentiak, Patricia A.; Needleman, Richard; Brusilow, William S. A. (2012-12-01). "Effect of Sex on Lifespan, Disease Progression, and the Response to Methionine Sulfoximine in the SOD1 G93A Mouse Model for ALS". Gender Medicine. 9 (6): 524–535. doi:10.1016/j.genm.2012.10.014. ISSN   1550-8579. PMID   23217569.
  5. ↑ Krajewski, W. W.; Jones, T. A.; Mowbray, S. L. (18 July 2005). "Structure of Mycobacterium tuberculosis glutamine synthetase in complex with a transition-state mimic provides functional insights". Proceedings of the National Academy of Sciences. 102 (30): 10499–10504. Bibcode:2005PNAS..10210499K. doi: 10.1073/pnas.0502248102 . PMC   1180770 . PMID   16027359.
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