C J Bates, MRC Human Nutrition Research,
© 2005 Elsevier Ltd. All rights reserved.
The discovery of vitamin K as an essential nutrient arose in the late 1920s from Henrik Dam's studies of sterol metabolism. He observed that chicks fed a fat-free diet developed subcutaneous hemorrhages and anemia. A lipid extract of liver or of certain plant tissues was curative, and by 1935 he claimed discovery of a new vitamin in these extracts that he named 'vitamin K' from the German Koagulation. By the late 1930s, two chemically similar forms of the vitamin from different sources were recognized, namely phylloquinone or K1 and menaquinone or K2, which had been isolated from alfalfa and from putrefied fish meal, respectively (Figure 1). Phyllo-quinone, with its saturated phytyl side chain, is now understood to be the sole representative of vitamin K that occurs in plant tissues, especially in green leafy ones, where it acts as a component of the electron transport chain. The menaquinones, or MK-n, by contrast, comprise a broad family of representatives that have a variable length, unsatu-rated side chain, and are composed of one or more (sequential) isoprene units in place of the saturated phytyl side chain. These menaquinones can be produced by certain types of bacteria, both in the large bowel of animals and at other locations where they may contribute to human food sources of menaqui-nones. Germ-free rats become vitamin K deficient more readily than their conventional counterparts, and they can develop very low hepatic MK-4 levels. The specific menaquinone with the same side chain length as phylloquinone is called menatetranone, or MK-4, and this is produced commercially for human medication, especially in Japan. There is evidence that phylloquinone can be converted to MK-4 in animals and humans. Most bacterially synthesized menaquinones have longer side chains, typically 7-9 isoprene units and up to 13, which are indicated by 'n' in the MK-n shorthand notation. A synthetic homolog of phylloquinone, K1(25), is not found in nature and can therefore be used as an internal standard in the chromatographic separation and quantitation of vitamin K. Menadione, a water-soluble form of the vitamin that has a single methyl group in place of the side chain, has vitamin K activity (it can be converted to menatetranone in vivo) and is used in animal feeds, but it is not used in humans because of its toxicity at high doses.
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