PMID- 23844795 OWN - NLM STAT- MEDLINE DCOM- 20140527 LR - 20220318 IS - 1755-148X (Electronic) IS - 1755-1471 (Linking) VI - 26 IP - 6 DP - 2013 Nov TI - Neutral pH and copper ions promote eumelanogenesis after the dopachrome stage. PG - 817-25 LID - 10.1111/pcmr.12137 [doi] AB - The diversity of pigmentation in the skin, hair, and eyes of humans has been largely attributed to the diversity of pH in melanosomes with acidic pH being proposed to suppress melanin production. Tyrosinase has an optimum pH of 7.4 and its activity is suppressed greatly at lower pH values. The first step of eumelanogenesis is the oxidation of tyrosine to dopachrome (DC) via dopaquinone. However, how eumelanogenesis is controlled by pH beyond this stage is not known. In this study, we examined the effects of pH (5.3-7.3) on the conversion of DC to 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and the subsequent oxidation of DHI and DHICA to form eumelanin. The effects of Cu(2+) ions on those reactions were also compared. The results indicate that an acidic pH greatly suppresses the late stages of eumelanogenesis and that Cu(2+) ions accelerate the conversion of DC to DHICA and its subsequent oxidation. CI - (c) 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Ito, Shosuke AU - Ito S AD - Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi, Japan. FAU - Suzuki, Natsumi AU - Suzuki N FAU - Takebayashi, Shiori AU - Takebayashi S FAU - Commo, Stephane AU - Commo S FAU - Wakamatsu, Kazumasa AU - Wakamatsu K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130805 PL - England TA - Pigment Cell Melanoma Res JT - Pigment cell & melanoma research JID - 101318927 RN - 0 (Indolequinones) RN - 0 (Indoles) RN - 0 (Ions) RN - 0 (Melanins) RN - 12627-86-0 (eumelanin) RN - 3571-34-4 (dopachrome) RN - 4790-08-3 (5,6-dihydroxy-2-indolylcarboxylic acid) RN - 789U1901C5 (Copper) RN - Z3OC8499KG (5,6-dihydroxyindole) SB - IM MH - Biosynthetic Pathways/drug effects MH - Copper/*pharmacology MH - Humans MH - Hydrogen-Ion Concentration/drug effects MH - Indolequinones/*metabolism MH - Indoles/chemistry/metabolism MH - Ions MH - Kinetics MH - Melanins/*biosynthesis OTO - NOTNLM OT - copper OT - dopachrome OT - dopachrome tautomerase OT - eumelanin OT - melanin OT - pH EDAT- 2013/07/13 06:00 MHDA- 2014/05/28 06:00 CRDT- 2013/07/13 06:00 PHST- 2013/04/01 00:00 [received] PHST- 2013/07/08 00:00 [accepted] PHST- 2013/07/13 06:00 [entrez] PHST- 2013/07/13 06:00 [pubmed] PHST- 2014/05/28 06:00 [medline] AID - 10.1111/pcmr.12137 [doi] PST - ppublish SO - Pigment Cell Melanoma Res. 2013 Nov;26(6):817-25. doi: 10.1111/pcmr.12137. Epub 2013 Aug 5.