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Cobalamin-related redox metabolic pathways in neuronal cells.

By Yiting Zhang (391974), Nathaniel W. Hodgson (380202), Malav S. Trivedi (380203), Hamid M. Abdolmaleky (160530), Margot Fournier (260993), Michel Cuenod (3312297), Kim Quang Do (847670) and Richard C. Deth (380205)


<p>Endocytosis brings TC-bound Cbl species to lysosomes where axial ligands are removed by MMACHC and MeCbl or AdoCbl are subsequently formed by SAM and ATP-dependent pathways, respectively. MeCbl is a required cofactor for methionine synthase, whose activity supports a large number of methylation reactions, including DNA methylation, as well as dopamine-stimulated phospholipid methylation, carried out by the D4 dopamine receptor (D4R). AdoCbl supports MMACoA mutase in mitochondria. Cysteine, which is rate-limiting for GSH synthesis, can be provided either by cellular uptake via the cysteine/glutamate transporter EAAT3 (excitatory amino acid transporter 3) or by transsulfuration of HCY via cystathionine. The latter pathway is restricted in human brain, increasing the importance of growth factor-dependent cysteine uptake by EAAT3.</p

Topics: Biological Sciences, Science Policy, Low levels, brain vitamin B 12 status, 19 weeks, substrate homocysteine, Brain development, Cbl species, AdoCbl levels, methylmalonylCoA mutase, antioxidant glutathione, 43 control subjects, hcy, Total Cbl, vitamin B 12, antioxidant demand, GSH deficiency, vitamin B 12 status, 80 years, Decreased Brain Levels, MS activity, subjects MeCbl, brain samples, GSH levels, 60 yrs, MeCbl levels
Year: 2016
DOI identifier: 10.1371/journal.pone.0146797.g001
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Provided by: FigShare
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