Tetrahydrofolate cobalamins metabolism

Metabolism and Mobilization. On entry of vitamin B 2 into the cell, considerable metaboHsm of the vitamin takes place. Co(III)cobalamin is reduced to Co(I)cobalamin, which is either methylated to form methylcobalamin or converted to adenosylcobalamin (coenzyme B>22)- The methylation requires methyl tetrahydrofolate. 

Figure 21-2. Metabolism of homocysteine. BHMT, betaineihomocysteine methyl-transferase CBS, cystathionine P-synthase Cob, cobalamin CTH, cystathionine y-lyase DHF, dihydrofolate DMG, dimethylglycine FAD, flavin adenine dinucleotide MAT, methionine adenosyltransferase 5-MTHF, 5-methyltetrahydrofolate 5,10-MTHF, 5,10-methylenetetrahydrofolate MTHFR, methylenetetrahydrofolate reductase MS, methionine synthase MTRR, methionine synthase reductase MTs, methyl transferases PLE pyridoxal phosphate SAH, S-adenosylhomocysteine SAHH, SAH hydrolase SAM, 5-adenosylmethionine SHMT, serine hydroxymethyltransferase THF, tetrahydrofolate Zn, zinc.

Methylation of homocysteine by 5-methyltetrahydrofolate-homocysteine methyl reductase depends on an adequate supply of 5-methyltetrahydrofoIate. The unmethylated folate is recycled in a cobalamin-dependent pathway, by remethylation to 5,10-methylene-tetrahydrofolate, and subsequent reduction to 5-methyltetrahydrofolate. The transferase enzyme, also named 5,10-methyltretrahydrofolate reductase catalyzes the whole cycle [3,91]. S-adenosylmethionine and 5-methyltetrahydrofolate are the most important methyl unit donors in biological system. S-adenosylmethionine is reported to regulate methylation and transsulfuration pathways in the homocysteine metabolism [3,91]. 

Metabolism of cobalamins in mammalian cells. Note the compartmentalization of the synthesis of the two coenzymes adenosylcobalamin (AdoCbl) synthesis occurs in mitochondria, whereas that of methylcobalamin (MeCbl) occurs in cytoplasm. TCII, Transcobalamin II OH-Cbl, hydroxocobalamin T, transport protein for TCII-OHCbl complex FH4, MeFH4, tetrahydrofolate and methyltetrahydrofolate, respectively Cbl, a cobalamin in which the ligand occupying the sixth coordination position of the cobalt is not known. The numerical superscripts adjacent to some of the cobalamins indicate the oxidation state of the cobalt ion. Cobalamins in the +1, +2, and +3 oxidation states are also known as Bn, B 2, and Bi2j, respectively. 

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