5 -deoxy-5 -adenosylcobalamin

AdoCbl 5 -Deoxy-5 -adenosylcobalamin, adenosylcobalamin, coenzyme B12 Cbl Cobalamin (DMB-cobamide)... 

Although numerous enzymatic reactions requiring vitamin B12 have been described, and 10 reactions for adenosylcobalamin alone have been identified, only three pathways in man have so far been recognized, one of which has only recently been identified (PI). Two of these require the vitamin in the adenosyl form and the other in the methyl form. These cobalamin coenzymes are formed by a complex reaction sequence which results in the formation of a covalent carbon-cobalt bond between the cobalt nucleus of the vitamin and the methyl or 5 -deoxy-5 -adenosyl ligand, with resulting coenzyme specificity. Adenosylcobalamin is required in the conversion of methylmalonate to succinate (Fig. 2), while methylcobalamin is required by a B12-dependent methionine synthetase that enables the methyl group to be transferred from 5-methyltetrahydrofolate to homocysteine to form methionine (Fig. 3). 

Two additional paramagnetic species have been detected in the L. leichmannii ribonucleotide reductase system. When adenosylcobalamin is incubated with a molar excess of reductase, a dithiol and either a ribo-nucleoside triphosphate or a deoxyribonucleoside triphosphate, the coenzyme is slowly degraded (ty2=30 min) to cob(II)alamin and o -deoxy-adenosine (78, 106). The ESR spectrum of the paramagnetic cobamide shows unique hyperfine and superhyperfine splitting not observed for cob(II)alamin in solution or as a solid. 

Reversibility in the reaction of (5)-2-aminopropanol allowed the identification of 5 -deoxyadenosine as a transiently and reversibly formed intermediate. Reaction of this substrate led to both cob(II)alamin and 5-deoxyadenosine in the steady state. Experiments with [5 - H2]adenosylcobalamin and (5)-2-amino[l- H2]propanol produced 5 -deoxy-[ H3]adenosine in the steady state, proving direct hydrogen transfer from the substrate to C5 of coenzyme Bi2. ... 

The cleavage of the Co—C bond in organocobalt compounds may occur by the reverse of the three pathways shown in equations (29)-(31). Bond homolysis has been particularly intensively studied, and may occur by photolysis or by thermolysis. Photolysis of the Co—C bond in methylcobalamin is accelerated by the presence of dioxygen, to give B,2a and formaldehyde. The slower rate of the anaerobic photolysis is suggested to result from recombination of Bjjr and methyl radicals. The photolysis of adenosylcobalamin gives 5 -deoxy-5, 8-cycloadenosine and adenosine-5 -carboxaldehyde in the presence of Oj, and the cyclized product only in the absence Of02. 

Another reaction that depends on adenosylcobalamin is the reduction of ribonucleoside triphosphates to the corresponding 2 -deoxy compounds, the building blocks of deoxyribonucleic acids. Methylcobalamin is formed, e. g., in the methyl-ation of homocysteine to methionine with N -... 

Coenzymes Bjj as cofactors catalyse two completely different types of reactions. Methylcobalamine (as with folacin) acts in some transmethylation reactions (such as biosynthesis of methionine from homocysteine), collaborates with foUc acid in the synthesis of DNA and red blood cells (biosynthesis of porphyrins) and in the fixation of carbon dioxide by some anaerobic acetogennic microorganisms. Enzymes using S -deoxy-S -adenosylcobalamine catalyse a number of isomerisations that are otherwise only viable with difficulty (1,2-rearrangements, such as the formation of succinyl-CoA from methyhnalonyl-CoA) and in some organisms they reduce ribonucleotides to deoxyiibonucleotides. 

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