The reaction is described as a nonimmune-mediated anaphylactoid reaction, with incidence of 3 per 10,000 treatments. The majority of reactions occurred when polyoxyethylated castor oil was used as the solubilizing agent. Non-human uses Forms not found in nature, and thus not "vitamins", are menadione and 4-amino-2-methyl-1-naphthol ("K5"). Menadione, a synthetic compound sometimes referred to as vitamin K3, is used in the pet food industry because once consumed it is converted to vitamin K2. The US Food and Drug Administration has banned this form from sale as a human dietary supplement because large doses have been shown to cause allergic reactions, hemolytic anemia, and cytotoxicity in liver cells. Research with K5 suggests it may inhibit fungal growth in fruit juices. Chemistry The structure of phylloquinone, Vitamin K1, is marked by the presence of a phytyl sidechain. Vitamin K1 has an (E) trans double bond responsible for its biological activity, and two chiral centers on the phytyl sidechain. Vitamin K1 appears as a yellow viscous liquid at room temperature due to its absorption of violet light in the UV-Vis Spectra. The structures of menaquinones, vitamin K2, are marked by the polyisoprenyl side chain present in the molecule that can contain four to 13 isoprenyl units. MK-4 is the most common form. The large size of Vitamin K1 gives many different peaks in mass spectroscopy, most of which involve derivatives of the naphthoquinone ring base and the alkyl side chain. Conversion of vitamin K1 to vitamin K2 In animals, the MK-4 form of vitamin K2 is produced by conversion of vitamin K1 in the testes, pancreas, and arterial walls. While major questions still surround the biochemical pathway for this transformation, the conversion is not dependent on gut bacteria, as it occurs in germ-free rats and in parenterally administered K1 in rats. There is evidence that the conversion proceeds by removal of the phytyl tail of K1 to produce menadione (also referred to as vitamin K3) as an intermediate, which is then prenylated to produce MK-4. Physiology In animals, vitamin K is involved in the carboxylation of certain glutamate residues in proteins to form gamma-carboxyglutamate (Gla) residues. The modified residues are often (but not always) situated within specific protein domains called Gla domains. Gla residues are usually involved in binding calcium, and are essential for the biological activity of all known Gla proteins. 17 human proteins with Gla domains have been discovered; they play