The Levels of Nitric Oxide in Megaloblastic Anemia/Megaloblastik Anemide Nitrik Oksit Duzeyleri (Research Article) (Report)

The Levels of Nitric Oxide in Megaloblastic Anemia/Megaloblastik Anemide Nitrik Oksit Duzeyleri (Research Article) (Report)

Introduction Megaloblastic anemia is characterized by megaloblastic erythropoiesis and is secondary to decreased activity of methionine synthase, one of two mammalian enzymes that requires vitamin B12 (cobalamin) as a cofactor. Methionine synthase catalyzes the transfer of the methyl group of 5-methyltetrahydrofolate to homocysteine via a methylcobalamin intermediate with cycling of cobalamin between the +1 valency state cobalamin and the +3 valency state cobalamin [1,2]. Methyltetrahydrofolate is the major intracellular storage form of folates, and its synthesis from 5,10-methylene tetrahydrofolate is essentially irreversible in vivo [2,3]. Thus, decreased methionine synthase activity leads to trapping of intracellular folates as 5-methyltetrahydrofolate, and the megaloblastic anemia of vitamin B12 deficiency is virtually indistinguishable from the megaloblastosis of folate deficiency [4]. Nitric oxide (NO) is produced by most cell types and regulates a diverse array of biological functions [5]. NO has been reported to inhibit methionine synthase activity in vitro [6-8], it might be expected to bind to the cobalt in cobalamin because (i) NO binds tightly to the iron in heme; (ii) ferrous heme and cbl (III) are isoelectronic; and (iii) in both heme and cobalamin, the metal ion is coordinated to four in-plane nitrogen atoms of a tetrapyrrole ring and has two out-of-plane ligands [2]. In Literatur published that NO inhibits methionine synthase activity in vivo and that NO produced by three different pharmacological agents or produced physiologically by rat C6 glioma cells inhibits carbon flow through the folate pathway [4].

The Levels of Nitric Oxide in Megaloblastic Anemia/Megaloblastik Anemide Nitrik Oksit Duzeyleri (Research Article) (Report)

The Levels of Nitric Oxide in Megaloblastic Anemia/Megaloblastik Anemide Nitrik Oksit Duzeyleri (Research Article) (Report) | | 4.5