Chapter 10: Tocopherols in Human Health: The Unique Chemistry and Role of γ-Tocopherol

Vitamin E (α-tocopherol)has been recognized for nearly a century as an essential vitamin responsible for reducing damage associated with oxidative species in membranes, whereas, only in the last two decades has the role of γ-tocopherol in animals begun to receive appropriate attention. γ-Tocopherol is the primary tocopherol consumed in the American diet and is found in micromolar concentrations in the human bloodstream. Nitric oxide (NO)is endogenously produced as a signaling molecule and in larger quantities to fight infectious agents. NO can be converted in vivo to the peroxynitrite radical, peroxynitrite, and nitrogen dioxide, which are highly reactive oxidants that can lead to significant mutagenic cellular damage. There is compelling evidence to suggest that the unique antioxidant properties of γ-tocopherol may specifically and preferentially target these oxidants, thereby reducing mutagenic events. There is also intriguing evidence from experimental and epidemiologic data that suggests γ-tocopherol levels are physiologically regulated and rise in response to inflammation, various disease states, and vitamin deficiencies. γ-Tocopherol appears to be an essential component of cellular defense against endogenously generated nitrogenous oxidants and future research should be directed toward determining the long-term consequences of γ-tocopherol deficiency in order to define its potential designation as an essential vitamin, separate from that of Vitamin E.