Dioxyphenylalanine

DIOXYPHENYLALANINE, 3-,4-dioxy-phenyl-α-aminopropionic acid, C₆H₃(OH)₂CH₂CH(NH₂)COOH, abbreviated at the suggestion of Bloch as "dopa" (from di-oxy-phenyl-alanin = "Dopa"), serves in the animal organism as a source for the formation of dark pigments, melanins, which impart color to various tissues, mainly of epidermal origin (skin, hair, insect wings, etc.). The pigment-forming cells contain a special enzyme, "dopa oxidase," which oxidizes dioxyphenylalanine into dark-colored products. This enzyme is strictly specific and does not act even on substances very close to dioxyphenylalanine in chemical structure (tyrosine, homogentisic acid, pyrocatechol, adrenaline). The action of dopa oxidase is revealed when skin sections are placed in a dioxyphenylalanine solution (sections are prepared by freezing, since the enzyme loses activity when embedded in paraffin or celloidin). In this process, the basal cells of the epidermis and the cells of the hair follicles are stained a more or less dark color, corresponding to the content of dopa oxidase in them. The latter is particularly abundant in the cells of pigment spots (naevus pigmentosus), and it has also been found in melanomas. In the skin of albinos, as well as in non-pigmented areas of the skin (vitiligo, animals with spotted coloration), the reaction for dopa oxidase does not occur, just as it does not in the pigment cells of the retina and meninges. Based on the content of dopa oxidase in cells, it was initially thought possible to distinguish cells capable of forming melanin from cells containing pigment merely as a result of phagocytosis; however, at present it is believed that the absence of dopa oxidase in a cell does not argue against the possibility that this cell could have formed melanin, since the absence of the enzyme is perhaps explained by the fact that the pigment formation process has already ended here (Walthard). Bloch views dioxyphenylalanine as one of the end products of pyrocatechol transformations. Normally, the greater part of the latter in the adrenal glands is converted into adrenaline, whereas in case of dysfunction of these glands, it accumulates in excess in the blood and is converted by pigment cells into melanin. This could serve as the cause of the dark ("bronze") coloration of the skin in Addison's disease. Bloch also attributes the greying of hair to the disappearance of dopa oxidase, as a result of which pigmented hairs are replaced by uncolored ones. Dioxyphenylalanine has been found in the integuments of insects (wings of cockchafers, butterflies), where it serves as a chromogen (source of pigment formation). The role of dioxyphenylalanine and dopa oxidase in pigmentation phenomena cannot be considered finally established, since there are indications that boiled tissues also give a reaction with dioxyphenylalanine, as do cells that do not normally form pigment (erythrocytes, eosinophils, vascular endothelial cells, Kupffer cells). However, the enzymatic nature of melanin formation from dioxyphenylalanine is supported by the specificity of the action of dopa oxidase, its sensitivity to hydrocyanic acid, acids and alkalis, etc.; lipid solvents (ether, chloroform, benzene) do not affect the enzyme.

Dioxyphenylalanine, similarly to adrenaline, which is also a pyrocatechol derivative, upon parenteral administration causes a strong increase in blood sugar content, reaching over 100% of the initial value. In this case, only the 3-,4-isomer proved active; the 2,4- and 2,5-isomers do not possess this action at all (Hirai). The action of dioxyphenylalanine is manifested in quantities of about 0.1 g per 1 kg of animal weight.