Fig. 1
From: Adult-onset CblC deficiency: a challenging diagnosis involving different adult clinical specialists
Schematic representation of cobalamin metabolism. Dietary vitamin B12 (Cbl) is bound by intrinsic factor (IF) in the stomach, the vitamin B12-instrinsic factor complex is absorbed by enterocytes in the ileum through the cubam receptor, formed by cubilin (CUBN) and amnionless (AMN). Cobalamin is then transferred onto transcobalamin 2 (TCN2) and transported in the bloodstream. The transcobalamin 2-cobalamin complex is taken up by hepatocytes through the TC2 receptor (CD230) and transferred to lysosomes, from which it is released by the membrane-bound transport proteins LMBD1 and ABCD4 and processed by MMACHC (whose transcription is controlled by HCFC1). MMADHC binds to MMACHC and then processed cobalamin is either directed towards Methylcobalamin (MeCbl) synthesis through methionine synthase reductase (MTRR) or to the mitochondrion, where Adenosylcobalamin (AdoCbl) is synthetized thanks to MMAA and MMAB proteins. MeCbl is a cofactor for the enzyme methionine synthase (MTR), involved in remethylation from homocysteine to methionine, while AdoCbl is a cofactor of methylmalonyl-CoA mutase (MMUT), which catalyzes the transformation of L-Methylmalonyl-CoA (MMA-CoA) into Succynil-CoA, which can then be used in the Krebs cycle [2]