Figure 3.

The GNMT salvage pathway. GNMT binds to and may be inhibited by MTHF. Therefore, when SAM levels increase, MeTHFR inhibition leads to a decrease in free MTHF and dissociation of the complex GNMT–MTHF. The consequent rise in free GNMT prevents the increase of SAM level. The decrease of SAM concentration is associated with a fall in free GNMT and with a release of MTHFR inhibition, leading to a rise in MTHF availability. The latter may be used for SAM resynthesis, GSH synthesis, and a rise in folate content. The blue arrows indicate activation; the red blunt arrows indicate inhibition; the black arrows indicate increase/decrease.