Methionine Synthase

• methionine synthase = synthesizes methionine by adding a methyl group to homocysteine
• activated methyl cycle:

  A) methyltetrafolate

  B) folate

  C) methionine synthase

  D) homocysteine

  E) SAM

  F) SAH

  G) hydrolysis

  H) SAM

  
• cobalamin = vitamin B12, an important cofactor for methionine synthase, where it picks up a methyl group and acts as a methyl donor; contains a central cobalt atom that goes between the 1+ and 3+ oxidation states when methylated
• the path of methyl in methionin synthase:

  1. transferred from CH3-THF (methyltetrahydrofolate) to cobalamin (vitamin B12)
  2. transferred from the now CH3-Co(III) (methylated cobalamin) to homocysteine, which becomes methionine!
• methionine synthase reactions

  A) THF

  B) THF

  C) (I)

  D) (II)

  E) (III)

  F) homocysteine

  G) SN2

  H) SN2

  I) SAM + e-

  J) SAH

  
• methionine synthase domains

  1. B12 domain: binds B12, also contains a cap to help protect the Co(I) of B12 from being oxidized to Co(II)
  2. CH3-THF domain: bind CH3-THF and picks up CH3 from THF and gives to B12
  3. Hcy domain: transfer of CH3 from B12 to homocysteine (Hcy)
  4. SAM domain: in case of accidental oxidation of Co(I) to Co(II), regenerates or reactivates to Co(III) by picking up e- and attaching CH3 from SAM (makes CH3-Co(III))