Melanogenesis in human melanomas.
A number of biochemical aspects of melanogenesis were studied in 15 variously melanized human melanomas. The tryosinase activity was correlated with the degree of melanoma varied from 3,667 to 46,183 tryosinase units, in partially melanotic melanoma it varied from 14 to 75 tryrosinase units. The subcellular distribution of tryrosinase activity was limited to the particulate fraction )144,000 x g) of the partially melanotic and amelanotic melanomas. However, the melanotic melanomas contained the enzyme in both particulate and soluble fractions, with the greater tyrosinase activity in the particulate fraction. Electrophoretic resolution of tyrosinase isozymes  in the soluble fraction or lipase-solubilized tyrosinase derived from the particulate fraction revealed three isozymes in melanotic melanomas. The isozyme of intermediate mobility always was the dominant form. In partially melaotic melanomas, the solubilized tyrosinase showed six isozymes. Three were similar to those of melanotic melanomas. The remaining three isozymes showed slower mobilities, possibly with greater molecular weights than the isozymes derived from melanotic melanomas. Inhibitors of tyrosinase were present in melanomas. Increased tyrosinase activity occurred after storing the homogenate at 0-4degree, removing of supernatant from the homogenate sediment, and washing the 144,000 x g particulate fraction, which suggested the presence of water-soluble, loosely bound inhibitor (s) in the soluble fraction of partially melanotic melanoma. Another inhibitor was released from the 144,000 x g particulate fraction of melanotic melanoma after lipase digestion. These substances inhibit both the isolated dominant tyrosinase isozyme(human) and mushroom tyrosinase. As inhibition of tyrosinase activity may produce regression of abnormal cell growth, the inhibitors may provide an approach to melanoma chemotherapy.
D004156:Catechol Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002458:Cell Fractionation; D003080:Cold Temperature; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004589:Electrophoresis, Disc; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D008545:Melanoma / Q000201:enzymology / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D007527:Isoenzymes; D008543:Melanins; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D004156:Catechol Oxidase