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Cobalamins : an update of fundamental and clinical data Volume 2, issue 2, Mars - Avril 1996

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Service d'hématologie biologique, hôpital Henri-Mondor, 94010 Créteil.

Cobalamins (Cbl) function as cofactors involved in the methionine synthesis and in the conversion of methylmalonic acid to succinic acid. Cbl are bound at each step of their metabolism to specific proteins : intrinsic Factor (IF), glycoprotein that mediates Cbl absorption across the ileum via a specific receptor, has been localized in gastric parietal cells but also in salivary glands, antral G cells, endothelium cells… Haptocorrins (HC), including vary glands, antral G cells, endothelium cells… Haptocorrins (HC), including transcobalamins (TC) I and III, glycoproteins found in many secretions could function as antibacterial agents. TCII polypeptide produced by various cells, intestine, bone marrow, endothelium…, promotes cellular uptake of Cbl through a specific receptor. On the basis of cDNA and aminoacid sequence, some structural similarities were found between IF and HC, located on chromosome 11 and also TCII located on chromosome 22. Diseases related to Cbl deficiency or to congenital abnormalities of Cbl usually revealed by a macrocytic megaloblastic anemia can also be evidenced by neurological or neuropsychyatric complications even without anemia and/or macrocytosis. Among Cbl malabsorpsions, pernicious anemia is an autoimmune gastritis, associated to parietal cells autoantibodies specifically directed against the proton pump H+/K+ ATPase and to IF autoantibodies at a lower rate. Imerslund disease, a congenital malabsorption of Cbl could be due to a defect of synthesis and/or expression of the ileal receptor. In TCII deficiencies, inducing neonatal megaloblastic anemia, the TCII gene is normal but no expression of mRNA and protein was found. Interest has been recently focused on sensitive and early indicators of Cbl deficiency, such as elevation of serum methylmalonic acid and homocysteine as well decrease of holoTCII, fraction of TCII binding endogenous Cbl. For treatment, hydroxoCbl better retained in tissues and more available to cells replace more and more cyanoCbl which can be toxic in some situations. In vitro, hydroxoCbl has been shown to inhibit HIV infection in normal human monocyte and lymphocyte and can be an adjuvant treatment in HIV infection.