Vitamin B12

O'Leary F, et al. Nutrients, 2010, 2(3), 299-316.

· Vitamin B12 and neural tube defects (NTDs)
Insufficient vitamin B12 levels are considered risk factors for NTDs because low vitamin B12 levels mean that folic acid necessary for DNA synthesis remains stuck in the cycle of methylation and cells do not replicate. People who are low in vitamin B12 have a 2-4 times increased risk of neural tube defects, research has shown.
· Vitamin B12 and heart disease (CVD)
Meta-analyses implicated the association of tHcy and CVD risk. Taking 0.02-1 mg/day of vitamin B12 will lower tHcy about 7% and folic acid will lower risk by 10-30%.
· Vitamin B12 and cognitive decline
Vitamin B12 levels are measured as part of the dementia screen but it's not clear what subclinical vitamin B12 levels do for cognitive function. In a meta-analysis and review, the link between tHcy and Alzheimer's disease was explained by low vitamin B12, B6 and folate.
· Vitamin B12 and Osteoporosis
B vitamin supplementation was positive for BMD in osteoporotic patients with high tHcy and in stroke patients at high risk of osteoporosis, but did not increase BMD in a healthy elderly group or in a secondary analysis of the CVD Reduction HOPE trial.

Randaccio L, et al. Molecules, 2010, 15(5), 3228-3259.

Bioconjugates can be prepared relatively easily using vitamin B12 compounds (cobalamins, XCbl) where these functionalities can be covalently attached to appropriately designed imaging or cytotoxicity markers.
· Cobalamin Conjugation Methods
Cobalamin conjugation can be achieved through several methods:
Reaction with carboxylic groups generated by hydrolyzing peripheral corrin amide side chains.
Esterification at the 2'-OH or 5'-OH positions of cobalamin's ribose moiety; Reductive alkylation at the β-axial position of the Co(III) center; Coordination to the nitrogen atom of the β-axial CN group in CNCbl.
· Applications of Vitamin B12 Bioconjugates
A study demonstrated that a radiolabeled bioconjugate can target various tumor cells by binding to haptocorrin, avoiding undesirable accumulation in organs like the kidneys, which are primary TC-Cbl storage sites. Importantly, bioconjugates with appropriate spacer lengths (n < 4) bind to HC and IF but not TC.
Recently, two bioconjugates, CNCbl-DTPA-Gd and CNCbl-TTHA-Gd, were synthesized and characterized. While CNCbl-DTPA-Gd can release significant amounts of free Gd3+ ions in vitro, the more stable CNCbl-TTHA-Gd cannot. The internalization of toxic Gd3+ ions into human myelogenous leukemia K562 cells at cytotoxic levels leads to a substantial decrease in tumour cell viability.