Cobalamin in inflammation III - Glutathionylcobalamin and methylcobalamin/adenosylcobalamin coenzymes: The sword in the stone? How cobalamin may directly regulate the nitric oxide synthases

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Abstract

Several mysteries surround the structure and function of the nitric oxide synthases (NOS). The NOS oxygenase domain structure is unusually open with a large area of solvent that could accommodate an unidentified ligand. The exact mechanism of the two-step five-electron monoxygenation of arginine to NG-hydroxy-l-arginine, thence to citrulline and nitric oxide (NO), is not clear, particularly as arginine/NG-hydroxy-l-arginine is bound at a great distance to the supposed catalytic heme Fe [III], as the anti-stereoisomer. The Return of the Scarlet Pimpernel Paper proposed that cobalamin is a primary indirect regulator of the NOS. An additional direct regulatory effect of the 'base-off' dimethylbenzimidazole of glutathionylcobalamin (GSCbl), which may act as a sixth ligand to the heme iron, promote Co-oriented, BH4/BH3 radical catalysed oxidation of l-arginine to NO, and possibly regulate the rate of inducible NOS/NO production by the NOS dimers, is further advanced. The absence of homology between the NOS and methionine synthase/methylmalonyl CoA mutase may enable GSCbl to regulate both sets of enzymes simultaneously by completely separate mechanisms. Thus, cobalamin may exert central control over both pro- and anti-inflammatory systems. © 2007 Informa UK Ltd.

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Wheatley, C. (2007). Cobalamin in inflammation III - Glutathionylcobalamin and methylcobalamin/adenosylcobalamin coenzymes: The sword in the stone? How cobalamin may directly regulate the nitric oxide synthases. Journal of Nutritional and Environmental Medicine, 16(3–4), 212–226. https://doi.org/10.1080/13590840701791863

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