(Methionine synthase) reductase

[methionine synthase] reductase
Methionine Synthase Reductase 2QTL.png
EC no.
CAS no.207004-87-3
Alt. namesMTRR
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

[Methionine synthase] reductase, or Methionine synthase reductase,[1] encoded by the gene MTRR, is an enzyme that is responsible for the reduction of methionine synthase inside human body. This enzyme is crucial for maintaining the one carbon metabolism, specifically the folate cycle. The enzyme employs one coenzyme, flavoprotein.


MTRR works by catalyzing the following chemical reaction:

2 [methionine synthase]-methylcob(I)alamin + 2 S-adenosylhomocysteine + NADP+ 2 [methionine synthase]-cob(II)alamin + NADPH + H+ + 2 S-adenosyl-L-methionine

The 3 products of this enzyme are methionine synthase-methylcob(I)alamin, S-adenosylhomocysteine, and NADP+, whereas its 4 substrates are methionine synthase-cob(II)alamin, NADPH, H+, and S-adenosyl-L-methionine.

Scavenger Pathway of Methionine Synthase Reductase to Recover Inactivated Methionine Synthase

Physiologically speaking, one crucial enzyme participated in the folate cycle is methionine synthase, which incorporated a coenzyme, cobalamin, also known as Vitamin B12. The coenzyme utilizes its cofactor, cobalt to catalyze the transferring function, in which the cobalt will switch between having 1 or 3 valence electrons, dubbed cob(I)alamin, and cob(III)alamin.

Over time, the cob(I)alamin cofactor of methionine synthase becomes oxidized to cob(II)alamin, rendering the enzyme inactive. Therefore, regeneration of the enzyme is necessary. Regeneration requires reductive methylation via a reaction catalyzed by (methionine synthase) reductase in which S-adenosylmethionine is utilized as a methyl donor, reducing cob(II)alamin to cob(I)alamin.[2]

Systematic naming[]

This enzyme belongs to the family of oxidoreductases, to be specific those oxidizing metal ion with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is [methionine synthase]-methylcob(I)alamin,S-adenosylhomocysteine:NADP+ oxidoreductase. Other names in common use include methionine synthase cob(II)alamin reductase (methylating), methionine synthase reductase, [methionine synthase]-cobalamin methyltransferase (cob(II)alamin, and reducing).


  1. ^ While including parentheses is the correct usage since this denotes the substrate being reduced, it is often omitted as omitting parentheses generally cause no confusion.
  2. ^ Leclerc, D.; Wilson, A.; Dumas, R.; Gafuik, C.; Song, D.; Watkins, D.; Heng, H. H. Q.; Rommens, J. M.; Scherer, S. W.; Rosenblatt, D. S.; Gravel, R. A. (1998-03-17). "Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria". Proceedings of the National Academy of Sciences. 95 (6): 3059–3064. Bibcode:1998PNAS...95.3059L. doi:10.1073/pnas.95.6.3059. ISSN 0027-8424. PMC 19694. PMID 9501215.