Cobalamin metabolism and its clinical aspects.

In 1970 we wrote: “The first major phase in the clinical investigation of vitamin B,? metabolism and its derangements began with the development and application of methods for the estimation of total Bl2 in tissues and body fluids and the assay of total serum vitamin Bl2 has been a routine diagnostic procedure for many years. Most of the information obtainable by such methods has been gained and it is now clear that we are in the early stages of a second phase, in which the further development and application of methods for the estimation of individual cobalamins will play an important part” [l] . We now believe that this second phase is well advanced; this we will leave the reader to judge. It must be remembered that although our laboratory is the only one which has a chromatographic technique for simultaneous estimation of individual blood and tissue cobalamins in regular use, there are other (enzymatic and also indirect) methods for estimating or monitoring individual cobalamin coenzymes, and, so far, all methods have provided results in agreement. Further advances may be expected when recently developed chromatographic techniques, such as high pressure liquid chromatography [2], are introduced, though detection and estimation of picogram quantities of cobalamins (1 pg = 1 x lo-’* g) will still be a problem. In this review, references, which could run into many hundreds, have been kept to a minimum by referring, where possible, only to key papers, relevant books and reviews. Useful general references to books or reviews are [3-1.51.