Simplified overview of B12 metabolism.

A simplified overview of vitamin B12 (B12) metabolism in mice with focus on the analysed parameters. Through binding to the transcobalamin receptor (TC–R), the TC–B12/cobinamide(Cbi) complex is internalised into the lysosomes. TC is degraded and B12 is transported into the cytoplasm by the lysosomal membrane transporter 1 (LMBRD1). Intracellular, B12 serves as cofactor for the mitochondrial methylmalonylCoA mutase (MUT) and the cytosolic methionine synthase (MS) that acts in coordination with methylenetetrahydrofolate reductase (MTHFR). In plasma, TC circulates partly unsaturated with B12 (UB12BC). If the B12 supply to the cell is insufficient, methylmalonic acid (MMA) and homocysteine (tHcy) accumulates in the blood. The transcript level of the boxed components were analysed by quantitative reverse–transcript (q–rt–) PCR and the circularised components were analysed biochemically in either tissue or blood (plasma) as indicated.