Reactions of Nitric Oxide with Vitamin B12and Its Precursor, Cobinamide
- 1 July 2003
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 42 (29), 8900-8908
- https://doi.org/10.1021/bi034469t
Abstract
Despite early claims that nitric oxide does not react with cobalamin under any circumstances, it is now accepted that NO has a high affinity for cobalamin in the 2+ oxidation state [Cbl(II)]. However, it is still the consensus that NO does not react with Cbl(III). We confirmed that NO coordinates to Cbl(II) at all pH values and that Cbl(III) does not react with NO at neutral pH. At low pH, however, Cbl(III) does react with NO by way of a two-step process that also reduces Cbl(III) to Cbl(II). To account for the pH dependence, and because of its intrinsic interest, we also studied reactions of NO with cobinamide [Cbi] in the 2+ and 3+ oxidation states. Both Cbi(II) and Cbi(III) react readily with NO at all pH values. Again, Cbi(III) is reduced during the process of coordinating NO. Compared to cobalamin, cobinamide lacks the tethered 5,6-dimethylbenzamidazolyl moiety bound to the cobalt ion. It may, therefore, be considered a “base-off” form of Cbl. To explain the reaction of Cbl(III) at low pH, we infer that the base-off form of Cbl(III) exists in trace amounts that are rapidly reduced to Cbl(II), which then binds NO efficiently. Base dissociation, we postulate, is the rate-limiting step. Interestingly, Cbi(II) has 100 times greater affinity for NO than does Cbl(II), proving that there is a strong trans effect due to the tethered base in nitrosyl derivatives of both Cbl(II) and Cbl(III). The affinity of Cbi(II) for NO is so high that it is a very efficient NO trap and, consequently, may have important biomedical uses.Keywords
This publication has 15 references indexed in Scilit:
- Nitric Oxide Inhibits Methionine Synthase Activity in Vivo and Disrupts Carbon Flow through the Folate PathwayJournal of Biological Chemistry, 2001
- Probing Protein Folding with Substitution-Inert Metal Ions. Folding Kinetics of Cobalt(III)-Cytochrome cJournal of the American Chemical Society, 1999
- STRUCTURE-BASED PERSPECTIVES ON B12-DEPENDENT ENZYMESAnnual Review of Biochemistry, 1997
- The Inactivation of Methionine Synthase in Isolated Rat Hepatocytes by Sodium NitroprussideEuropean Journal of Biochemistry, 1997
- In vitro inactivation of mammalian methionine synthase by nitric oxideEuropean Journal of Clinical Investigation, 1996
- Selective Oxygen Transfers with Iron(III) Porphyrin NitriteThe Journal of Organic Chemistry, 1996
- Evidence from Electron Paramagnetic Resonance Spectroscopy of the Participation of Radical Intermediates in the Reaction Catalyzed by Methylmalonyl-coenzyme A MutasePublished by Elsevier BV ,1995
- Cobalamin Analogues Are Present in Human Plasma and Can Mask Cobalamin Deficiency because Current Radioisotope Dilution Assays Are Not Specific for True CobalaminNew England Journal of Medicine, 1978
- Electronic spectral and magnetic susceptibility studies of nickel(II) and cobalt(II) carboxypeptidase A complexesJournal of the American Chemical Society, 1975
- Stereochemistry of nitrosylmetalloporphyrins. Nitrosyl-.alpha.,.beta.,.gamma.,.delta.-tetraphenylporphinato(1-methylimidazole)iron and nitrosyl-.alpha.,.beta.,.gamma.,.delta.-tetraphenylporphinato(4-methylpiperidine)manganeseJournal of the American Chemical Society, 1974