Marsh E N
Department of Chemistry, University of Michigan, Ann Arbor 48109-1055, USA.
Essays Biochem. 1999;34:139-54. doi: 10.1042/bse0340139.
The B12 or cobalamin coenzymes are complex macrocycles whose reactivity is associated with a unique cobalt-carbon bond. The two biologically active forms are MeCbl and AdoCbl and their closely related cobamide forms. MeCbl participates as the intermediate carrier of activated methyl groups. During the catalytic cycle the coenzyme shuttles between MeCbl and the highly nucleophilic cob(I)alamin form. Examples of MeCbl-dependent enzymes include methionine synthase and Me-H4-MPT: coenzyme M methyl transferase. AdoCbl functions as a source of carbon-based free radicals that are unmasked by homolysis of the coenzyme's cobalt-carbon bond. The free radicals are subsequently used to remove non-acid hydrogen atoms from substrates to facilitate a variety of reactions involving cleavage of carbon-carbon, carbon-oxygen and carbon-nitrogen bonds. Most reactions involve 1,2 migrations of hydroxy-, amino- and carbon-containing groups, but there is also one class of ribonucleotide reductases that uses AdoCbl. The structures of two cobalamin-dependent enzymes, methionine synthase and methylmalonyl-CoA mutase, have been solved. In both cases the cobalt is co-ordinated by a histidine ligand from the protein. The significance of this binding motif is presently unclear since in other cobalamin-dependent enzymes spectroscopic evidence suggests that the coenzyme's nucleotide 'tail' remains co-ordinated to cobalt when bound to the protein.
维生素B12或钴胺素辅酶是复杂的大环化合物，其反应活性与独特的钴-碳键有关。两种生物活性形式是甲基钴胺素（MeCbl）和腺苷钴胺素（AdoCbl）以及它们密切相关的钴胺酰胺形式。MeCbl作为活化甲基的中间载体发挥作用。在催化循环中，辅酶在MeCbl和高亲核性的钴胺素（cob(I)alamin）形式之间穿梭。依赖MeCbl的酶的例子包括甲硫氨酸合酶和甲基-H4-甲硫基嘌呤：辅酶M甲基转移酶。AdoCbl作为碳基自由基的来源，通过辅酶的钴-碳键的均裂而产生。这些自由基随后用于从底物上去除非酸性氢原子，以促进涉及碳-碳、碳-氧和碳-氮键断裂的各种反应。大多数反应涉及羟基、氨基和含碳基团的1,2迁移，但也有一类核糖核苷酸还原酶使用AdoCbl。两种依赖钴胺素的酶，甲硫氨酸合酶和甲基丙二酰辅酶A变位酶的结构已经得到解析。在这两种情况下，钴都由来自蛋白质的组氨酸配体配位。目前尚不清楚这种结合基序的意义，因为在其他依赖钴胺素的酶中，光谱证据表明辅酶的核苷酸“尾巴”在与蛋白质结合时仍与钴配位。
