Principles of Biochemistry, Volume 1 - A. Lehninger 1985

Biomolecules
Vitamins and Trace Elements: Their Role in Enzyme Function
Vitamin B12 is a precursor of coenzyme B12

Vitamin B12, the most complex of all Vitamins, has a rather unusual history. In 1926, two American physicians, George Minot and William Murphy, discovered that including large amounts of semi-raw Liver in the diet had a therapeutic effect on pernicious anemia, a severe and frequently fatal disease. Animals do not develop a similar condition. Significant progress in isolating the anti-anemia factor from liver was not achieved until the late 1940s, when Mary Shorb discovered a bacterium whose growth depended on this factor. Thus, bacterial growth rates could be used as a simple and rapid assay to measure the active factor's concentration. In 1948, E. Lester Smith (England), along with Edward Rickes and Karl Folkers (USA), obtained vitamin B₁₂ in crystalline form. However, it took another decade of X-ray crystallography to determine its Structure, which proved to be extremely complex (Fig. 10-15).

Vitamin B₁₂ differs from all other vitamins not only in its structural complexity, but also in containing cobalt, a trace element essential for the Organism. The vitamin B₁₂ derivative typically obtained during isolation is called cyanocobalamin because it contains a cyano group coordinated to the cobalt atom. The complex corrin ring system of vitamin B₁₂ (Fig. 10-15), to which the cobalt atom is coordinated, is chemically similar to the porphyrin ring system of heme and Hemoproteins (Section 8.2). In the coenzyme form of vitamin B₁₂, known as 5'-deoxyadenosylcobalamin, the cyano group is replaced by a 5'-deoxyadenosyl group (Fig. 10-15).

Vitamin B₁₂ is not synthesized by either plants or animals; it is produced exclusively by certain microorganisms. The daily requirement of a healthy human for this vitamin is minuscule—about 3 µg. The Role of vitamin B₁₂ in the Treatment of pernicious anemia is discussed in Chapter 26.

All Enzymes requiring coenzyme B₁₂ catalyze an interchange between a hydrogen atom bound to a carbon atom and a group (such as an alkyl, carboxyl, hydroxyl, or amino group) attached to an adjacent carbon atom (Fig. 10-16). Figure 10-16 illustrates a typical reaction requiring coenzyme B₁₂ (cobamide). Another coenzyme form of vitamin B₁₂, methylcobalamin, participates in certain Reactions Involving the transfer of methyl groups.

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Fig. 10-15. Vitamin B₁₂ and its coenzyme form, known as adenosylcobalamin (or coenzyme B₁₂). The cyano group (highlighted in red) is replaced in coenzyme B₁₂ by the 5'-deoxyadenosyl group (shown at the top of the figure).

Fig. 10-16 Reactions involving Coenzyme forms of vitamin B₁₂. A. Coenzyme B₁₂-dependent enzymes catalyze The transfer of a hydrogen atom from C1 to C2 in exchange for group X. B. A coenzyme B₁₂-dependent reaction catalyzed by methylaspartate mutase. Note that the H and X groups attached to adjacent carbon atoms exchange places with each other.