VITAMINS

Vitamin K is a fat-soluble vitamin and a well-known cofactor for γ-glutamyl carboxylase (GGCX), an enzyme that converts specific glutamic acid residues in several proteins to γ-carboxyglutamic acid (Gla) residues related to blood coagulation and bone formation in the vitamin K cycle. It has two major homologues, the plant-derived vitamin K_1 (phylloquinone: PK)and the bacterium-derived vitamin K_2 (menaquinone-n: MK-n). Among these homologues, MK-4 has attracted attention because of its interesting biological activities. For example, MK-4 showed additional biological actions related to gene transcription through the steroid and xenobiotic receptor (SXR), suppression of cancer cell proliferation, and so on. Therefore, we evaluated the biological action of vitamin K homologues with chemical techniques using heavy oxygen labeled, fluorescent labeled, and deuterated labeled analogues. Furthermore, we also elucidated new analogues with high rates of conversion to MK-4. Those analogues can be expected to lead to new drugs once the biological importance of MK-4 is clarified.

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The purpose of reference values for vitamin concentrations in serum, plasma and whole blood and the need for standardization of vitamin assay methods were described. The nutritional assessment of vitamin data is a comparative decision-making process in which a laboratory test result for an individual is compared with a reference value. Therefore, reliable reference values are required for all vitamin assays in clinical laboratory. The reference values should be provided by the candidate reference method or routine measurement procedure both of which have a demonstrated record of traceability of accuracy from the reference measurement procedure. The term "traceability chain" is used to refer to an unbroken chain of comparisons relating the routine measurement procedure to a certified concentration (expressed as SI unit) of the primary standard determined by the reference measurement procedure. The traceability chain was combined by the reference standard (e.g., NIST SRM) between the reference measurement procedure and the routine measurement procedure. The above process is referred to as "standardization". Nowadays, the reference measurement procedures are selected for measurements of folate and vitamin D in clinical specimens, and the candidate reference methods for vitamin A, vitamin D, vitamin E, vitamin B_1, vitamin B_<12>, folate and vitamin C. The reference values provided by the candidate reference method was available in vitamin A, vitamin D, vitamin E, vitamin B_1, vitamin B_<12>, folate and vitamin C. Decision limits, the analytical concentration that reflected the nutritional status of individuals as "deficiency", "marginal deficiency" or "adequate", for vitamin D, vitamin B_1, folate and vitamin C were also described.

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Various methods (microbiological assay, radioisotope dilution assay, high-performance liquid chromatography, chemiluminescence assay and so on) are used for vitamin B_<12> determination in foods and clinical materials. Although a biosensor based on surface plasmon resonance has been devised in the field of food analysis, the traditional microbiological assay is even now used worldwide. Human serum vitamin B_<12> was routinely determined by three fully-autoanalyzers: the ADVIA Centaur immunoassay system, Access immunoassay system, and Elecsys system are available in Japan. There are various problems to establish standardization of human serum vitamin B_<12> assay by these clinical laboratory analyzers.

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