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Kinetics of Cellular Cobalamin Uptake and Conversion: Comparison of Aquo/Hydroxocobalamin to Cyanocobalamin.
Fedosov, Sergey N; Nexo, Ebba; Heegaard, Christian W.
Afiliación
  • Fedosov SN; Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark.
  • Nexo E; Department of Clinical Medicine/Clinical Biochemistry, Aarhus University Hospital, 8200 Aarhus N, Denmark.
  • Heegaard CW; Department of Clinical Medicine/Clinical Biochemistry, Aarhus University Hospital, 8200 Aarhus N, Denmark.
Nutrients ; 16(3)2024 Jan 27.
Article en En | MEDLINE | ID: mdl-38337663
ABSTRACT
Cyanocobalamin (CNCbl) and aquo/hydroxocobalamin (HOCbl) are the forms of vitamin B12 that are most commonly used for supplementation. They are both converted to methylcobalamin (MeCbl) and 5'-deoxyadenosylcobalamin (AdoCbl), which metabolize homocysteine and methylmalonic acid, respectively. Here, we compare the kinetics of uptake and the intracellular transformations of radiolabeled CNCbl vs. HOCbl in HeLa cells. More HOCbl was accumulated over 4-48 h, but further extrapolation indicated similar uptake (>90%) for both vitamin forms. The initially synthesized coenzyme was MeCbl, which noticeably exceeded AdoCbl during 48 h. Yet, the synthesis of AdoCbl accelerated, and the predicted final levels of Cbls were MeCbl ≈ AdoCbl ≈ 40% and HOCbl ≈ 20%. The designed kinetic model revealed the same patterns of the uptake and turnover for CNCbl and HOCbl, apart from two steps. First, the "activating" intracellular processing of the internalized HOCbl was six-fold faster. Second, the detachment rates from the cell surface (when the "excessive" Cbl-molecules were refluxed into the external medium) related as 41 for CNCbl vs. HOCbl. This gave a two-fold faster cellular accumulation and processing of HOCbl vs. CNCbl. In medical terms, our data suggest (i) an earlier response to the treatment of Cbl-deficiency with HOCbl, and (ii) the manifestation of a successful treatment initially as a decrease in homocysteine.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vitamina B 12 / Hidroxocobalamina Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nutrients Año: 2024 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vitamina B 12 / Hidroxocobalamina Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nutrients Año: 2024 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Suiza