Abstract
Several studies suggest that the vitamin B12 (B12) transport system can be used for the cellular delivery of B12-conjugated drugs, also in long-term treatment Whether this strategy will affect the endogenous metabolism of B12 is not known. To study the effect of treatment with excess B12 or an inert derivative, we established a mouse model using implanted osmotic minipumps to deliver saline, cobinamide (Cbi) (4.25 nmol/h), or B12 (1.75 nmol/h) for 27 days (n = 7 in each group). B12 content and markers of B12 metabolism were analysed in plasma, urine, kidney, liver, and salivary glands. Both Cbi and B12 treatment saturated the transcobalamin protein in mouse plasma. Cbi decreased the content of B12 in tissues to 33–50% of the level in control animals but did not influence any of the markers examined. B12 treatment increased the tissue B12 level up to 350%. In addition, the transcript levels for methylenetetrahydrofolate reductase in kidneys and for transcobalamin and transcobalamin receptor in the salivary glands were reduced. Our study confirms the feasibility of delivering drugs through the B12 transport system but emphasises that B12 status should be monitored because there is a risk of decreasing the transport of endogenous B12. This risk may lead to B12 deficiency during prolonged treatment.
Highlights
Once absorbed from the intestine, vitamin B12loaded mice (B12) (B12) is transported to all cells to play its role as cofactor for B12 dependent enzymes
We report that infusion of Cbi leads to depletion of B12 from mice tissues and that overload with B12 leads to alterations in the metabolism of HCY
This is, to our knowledge, the first extensive overview of markers related to B12 status measured in the same group of Protein name Methionine synthase (MS) Methylenetetrahydrofolate reductase (MTHFR) Methylmalonyl-Coenzyme A mutase (MUT) Lysosomal cobalamin transporter (LMBRD1) Transcolabamin (TC) TC-receptor (TC-R) b-Actin
Summary
Once absorbed from the intestine, vitamin B12 (B12) is transported to all cells to play its role as cofactor for B12 dependent enzymes. These processes imply a coordinated action of several proteins and receptors, as outlined in Figure 1 (for a resent review, see [1]). TC and HC recognize different forms of B12. Human TC only binds the active forms of B12 while HC binds B12 analogues such as cobinamide (Cbi) [4]. Mouse TC have features common to both human TC and HC, since it promotes cellular uptake of B12 but at the same time mouse TC recognizes both B12 and Cbi [2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
