The 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase activity of human tyrosinase

Abstract

Melanin synthesis in mammals is catalysed by at least three enzymic proteins, tyrosinase (monophenol dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) and tyrosinase-related proteins (tyrps) 1 and 2, whose genes map to the albino, brown and slaty loci in mice, respectively. Tyrosinase catalyses the rate-limiting generation of L-dopaquinone from L-tyrosine and is also able to oxidize L-dopa to L-dopaquinone. Conversely, mouse tyrp1, but not tyrosinase, catalyses the oxidation of the indolic intermediate 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into the corresponding 5,6-indolequinone-2-carboxylic acid, thus promoting the incorporation of DHICA units into eumelanin. The catalytic activities of the human melanogenic enzymes are still debated. TYRP1 has been reported to lack DHICA oxidase activity, whereas tyrosinase appears to accelerate DHICA consumption, thus raising the question of DHICA metabolism in human melanocytes. Here we have used two different approaches, comparison of the catalytic activities of human melanocytic cell lines expressing the full set of melanogenic enzymes or deficient in TYRP1, and transient expression of TYR and tyr genes in COS7 cells, to demonstrate that human tyrosinase actually functions as a DHICA oxidase, as opposed to the mouse enzyme. Therefore, human tyrosinase displays a broader substrate specificity than its mouse counterpart, and might be at least partially responsible for the incorporation of DHICA units into human eumelanins.

Aluminum Facilitation of the Iron-Mediated Oxidation of DOPA to Melanin

“…61,62 Such DHICA-melanins have a higher chelating capacity and a more pronounced antioxidant oxidative ability than the DHI-melanins. 31,[63][64][65] Therefore, Al 3+ may also influence the melanin toxicity by means of increasing the ratio of DHI to DHICA.…”

Inhibitory Effects of Melanin Secretion on B16 Melanoma cell of Cordyceps militaris Water Extract

“…멜라닌의 생합성은 주로 타이로시나아제의 작용에 의해 이루어지며 타이로시나아제에 의해 생성이 촉진되는 동물 멜라닌은 페오멜라닌(yellow and red melanin)과 유멜라 닌(brown and black melanin)으로 구분된다 (Raper, 1928;Kobayashi et al, 1995;Mason, 1948;Olivares et al, 2001). 참고문헌…”

Making the invisible visible

“…Its mouse ortholog, mutations in which cause the brown phenotype, was identified as having dopachrome tautomerase activity [26]. The human version may not have that function [27].…”