472 PATHOLOGICAL PIGMENTATION 



strongly a melanin formation, and this has been cited as an example 

 of the production of melanin from hemoglobin. Carbone has proved, 

 however, that this malarial pigment is derived from hematin. The 

 amount of iron contained in melanin has been much investigated, as 

 bearing upon the question as to whether the melanin is derived from 

 hemoglobin or not, and the results obtained by the best methods indi- 

 cate that the amount of iron present is usually extremely small, and 

 often it is entirely absent; furthermore, the presence of iron is no 

 proof that the pigment is derived from hemoglobin, since other iron- 

 protein compounds undoubtedly exist,^ — especially nucleoproteins, 

 and chemical examination shows that melanin does not contain hemo- 

 pyrrole groups.^ 



Composition of Melanin. — The elementary composition of different specimens 

 of melanin examined by various observers has been found to vary greatly. This 

 probably depends on three factors : First, it is extremely difficult to obtain melanin 

 in a pure condition; second, the process of purification requires the action of strong 

 acids and alkalies, which undoubtedly modify the composition of the melanin; 

 thirdlj^, melanin is probably not a single substance of definite composition, but 

 includes several related biit different bodies. The values found varj' for carbon 

 from 48.95 to 60.02 per cent. ; for hydrogen from 3.05 to 7.57 per cent. ; for nitrogen, 

 8.1 to 13.77 per cent. Hofmeister gives, as a characteristic of melanins, that 

 their elementary molecular composition is always nearly in the proportions 

 N : H : C = 1 : 5 : 5. 



Gortner's^ studies have led him to accept the general principle that melanin 

 is formed through the action of an oxidase on an o.xidizable chromogen, but that 

 in keratinous structures there exist at least two types of melanins, one, a "nielano- 

 protein," soluble in dilute acids and existing dissolved in the keratins; the other, 

 insoluble in dilute acids, exists as pigment granules and is of unknown nature. 

 Piettre'"* believes that melanin from sarcoma of the horse consists of a protein 

 united to a pigment. Those whose studies of melanin formation have been made 

 with the microscope, state that the nucleus is active in the process, ^^ and some 

 find the melanin so closely related to the lipoids that they consider it a lipochrome.^^ 



A particularly prominent constituent of some melanins is sulphur,which has 

 been found in as high proportions as 10 per cent, in melanin from sarcomas, and 

 even 12 per cent, in sepia from the squid; in melanin from hair the sulphur is 

 usually about 2-4 per cent.; but in choroid melanin, and in some other forms, 

 sulphur seems to be absent. The proportions of sulphur obtained from the same 

 specimen purified by different methods show wide variations, and hence v. Fiirth 

 considers that neither the sulphur nor the iron are indispensable constituents of 

 the melanin. Probably the melanin molecule contains atom-complexes that have 

 a tendency to bind certain sulphur and iron compounds (e. g., cystine or hematin 

 derivatives). 



There is much reason to believe that the melanin is derived from certain groups 

 of the protein molecule that seem readily to form colored comjiounds. The aro- 

 matic compounds of the protein molecule, such as tyrosine, phenylalanine, and 

 tryptophane, readily condense with elimination of water and absorption of oxygen, 

 to produce dark-colored substances. When proteins are heated in strong hydro- 

 chloric acid, we obtain a dark-brown material, which closely resembles the melanins 

 both in elementary composition and in general properties, so that it is referred to 



8 Spiegler, Hofmeister's Beitr., 1907 (10), 253. 

 »Biochem. Bulletin, 1911 (1), 207; r6sum6. 



*" Compt. Rend. Acad. Sci., 1911 (153), 782; also see Reprint from 1st Internat. 

 Cong. Compar. Pathol., Paris, 1912. 



1' Htaffel, Verh. Deut. Path. Ges., 1907 (11), 136; Schultz, Jour. Med. Res., 

 1912 (26), 65. 



12 Dyson, Jour. Path, and Bact., 1911 (15), 298; Kreibich, Wien. klin. Woch., 

 1911 (24), 117. 



