Intracellular Processing and Utilization of Cobalamins

• Published in: Vitamin B12 Vol. 1; pp. 46 - 93
• Main Authors: Hannibal, Luciana, Jacobsen, Donald W
• Format: Book Chapter
• Language: English
• Published: United Kingdom CRC Press 2017; CRC Press LLC; Taylor & Francis Group
• Edition: 1
• Subjects: Biochemistry; MS Reductase; Corrin Ring; Methionine Synthase Reductase; Cpr; Cofactor Biosynthesis; Complementation Group; MS; Major Transcription Start Sites; Amino Acid Residues Arg-186; Amino Acid Residues; Methylmalonic Aciduria; Methionine Synthase; Amino Acid Residue His759; PNP; Methylmalonyl CoA Mutase; Mitochondrial Leader Sequence; Cobalt Center; ATP Dependent Reaction; GTP Hydrolysis; Co-C Bond; Methylmalonic Acid; Cytochrome P450 Reductase; Amino Acid Residue Gln131; Activation Domain
• ISBN: 1498706991; 9781498706995
• DOI: 10.1201/9781315119540-3

This chapter presents an intracellular cobalamin (Cbl) processing and trafficking and the synthesis and utilization of the two essential cofactors, methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl). The Cbl processing arose from ex vivo studies with fibroblasts from patients carrying inborn errors of Cbl metabolism. The expression of cobalamin deficiency type C (CblC) is also subject of epigenetic and transcriptional. The proteome of cells and plasma isolated from cblC patients share alterations in proteins involved in cellular detoxification, binding of glutathione metabolism, protein folding and cytoskeleton organization and assembly. An interaction between CblC, and methylmalonic aciduria type D and homocystinuria has been described by several laboratories. Synthesis of MeCbl is performed by cytosolic methionine synthase, and its intramolecular partner methionine synthase reductase. The energy of GTP hydrolysis is utilized to release inactive Cbl from the active site of B12-dependent methylmalonyl-CoA mutase during catalysis, which explains the inability of methylmalonic aciduria, type A patients to perform AdoCbl synthesis.