MTR and folate deficiency: Vitamin B12 deficiency is closely related to folate deficiency and can lead to megaloblastic anemia by impairment in the activity of methionine synthase (MTR) [109]: 5-methyl tetrahydrofolate cannot be converted to one-carbon donors required for purine and thymidine synthesis without vitamin B12 as a cofactor, thus interfering with DNA synthesis and erythrocyte production [136].