MELANIN 473 



as "artificial melanin" or "melanoid substance." These substances, like the 

 natural inelanins, when decomposed by fusing with caustic potash, yiehl skatolc, 

 indole, and pyrrole derivatives, whicli are undoubtetily derived from the 

 tyrosine and tryptophane of the protein molecule. Therefore, it seems probable 

 that both the melanoid substances and the true melanins are formed from the 

 chromojfen groups of the protein molecule through processes of condensation, 

 elimination of water, and the taking up of oxygen.'* 



In the sepia sacs of the cuttle-fish, in meal-worms which form a melanin-like 

 pigment, and in plants that produce the black Japanese lacquer, have been found 

 oxidizinq enzymes that have the property of producing black pigment by their 

 action upon tyrosine and other aromatic compounds. Neuberg" found that ex- 

 tracts of a melanosarcoma of the adrenal could produce pigment from epinephrine 

 and /3-oxyphenylethylamine, but not from tyrosine. The ink sacs of the squid 

 contain an enzyme forming a pigment from epinephrine, apparently through oxi- 

 dation and condensation. These enzymes may, therefore, possibly be responsible 

 for the production of melanin in animal tissues, by causing oxidative changes in 

 the chromogen groups of the protein molecule that are liberated by autolysis (see 

 "Tyrosinase"), v. Ftirth urges strongly the view that both normal and patho- 

 logical melanin formation depend upon the action of the tyrosinase or allied en- 

 zymes in conjunction with autolytic enzymes; the latter split free the chromogen 

 groups of the protein molecule, which are then oxidized by the tyrosinase, undergo 

 condensation, and take up sulphur- and iron-holding groups and also other organic 

 compounds, the entire complex forming the melanin. 



Bruno Bloch'^ has found that the occurrence of melanin in the skin corresponds 

 to the location of cells with the capacity of oxidizing 3.4-dioxyphenylalanine, 

 which is closely related in structure to epinephrine, and which he believes may be 

 the usual antecedent of melanin. He has found this oxidizing property exhibited 

 by the dark patches in variegated animals, but not by the white areas; the pig- 

 mented ocular structures do not oxidize this substance. 



Properties of Melanin. — When isolated in a pure condition, 

 melanin is a dark-brown substance of amorphous structure, no mat- 

 ter how black the material from which it is derived may be.**' It is 

 quite insoluble in all ordinary reagents except alkalies, in which some 

 melanins dissolve easily, and some with difficult3\ Strong boiling 

 hydrochloric acid scarcely affects non-protein melanins. By the 

 action of sunhght or oxichzing agents on melanin-containing sections 

 the pigment can be bleached out. The chief decomposition-products 

 formed on fusing with alkalies are indole, skatole, and "melanic 

 acid"; no cystine, leucine, tyrosine, or other amino-acids can be iso- 

 lated. Most authors, therefore, consider the melanins as heterocyclic 

 compounds standing in some relation to the indole nucleus. 



If melanin is injected subcutaneously into animals u'abbits and 

 guinea-pigs), there appears in the urine a substance which turns dark 

 brown after the urine has stood for some time (Kobert, Helman). 

 The pigment is apparently reduced, particularly by the liver, to a 

 colorless melanogen, which is eliminated in the urine. The same 

 process occurs when melanin is produced in excess and enters the 



'3 See Herzmark and von Furth, Biochem. Zeit., 1913 (49), 130. 



1* Zeit. f. Krebsforsch., 1909 (8), 195. 



15 Bloch and Ryhiner, Zeit. exp. Med., 1917 (5), 179; Zeit. physiol. Chem., 

 1917 (100), 226. 



'^ Spiegler (Hofmeister's Beitr., 1903 (4), 40) claims to have isolated from 

 white wool a white chromogen, closely related to melanin chemically, but Gortner 

 (Amer. Naturalist, 1910 (44), 497) believes this to be a decomposition product of 

 keratin, unrelated to melanin. 



