Pulse radiolysis studies of ortho-quinone chemistry relevant to melanogenesis.
The contributions of pulse radiolysis towards characterisation of unstable ortho-quinones relevant to melanogenesis are reviewed. The quinones discussed include dopaquinone, the precursor of both eumelanogenesis and phaeomelanogenesis, and 5-S-cysteinyldopaquinone, an early component of the phaeomelanogenic pathway. Redox exchange between dopaquinone and 5-S-cysteinyldopa is shown to be a determinant of the balance between eumelanogenesis and phaeomelanogenesis. Ortho-quinones resulting from the oxidation of tertiary N,N-dialkylcatecholamines cyclise to redox-inactive betaines which fail to autoactivate tyrosinase. This is consistent with the dopa detected during melanogenesis catalysed by tyrosinase being formed indirectly by a combination of dopaquinone intramolecular reductive addition to form leucodopachrome (cyclodopa), followed by redox exchange between remaining dopaquinone and leucodopachrome. Rapid tautomerism of the ortho-quinone of 4-cyanomethylcatechol to a redox-inactive quinomethane likewise inhibits tyrosinase autoactivation. The incorporation of trihydric phenol moieties in melanin is modelled by the reactions of several ortho-quinones with phloroglucinol, which itself is not directly oxidised by tyrosinase due to the meta-positioning of the hydroxyl groups. The importance of a susceptibility towards nucleophilic attack as well as a propensity to undergo redox-exchange, in the chemistry of melanogenic ortho-quinones, is emphasised.
Land
E J
EJ
CRC Drug Development Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK. eland@mighty-micro.co.uk
Ramsden
C A
CA
Riley
P A
PA
D016227:Benzoquinones / Q000737:chemistry; D002396:Catechols / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D003548:Cysteinyldopa / Q000737:chemistry; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry; D004789:Enzyme Activation; D006801:Humans; D008543:Melanins / Q000737:chemistry*; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000737:chemistry; D010084:Oxidation-Reduction; D010696:Phloroglucinol / Q000737:chemistry; D011675:Pulse Radiolysis / Q000379:methods; D011809:Quinones / Q000737:chemistry*
D016227:Benzoquinones; D002396:Catechols; D008543:Melanins; D011809:Quinones; D003548:Cysteinyldopa; D004295:Dihydroxyphenylalanine; C035157:dopaquinone; D010696:Phloroglucinol; D014442:Monophenol Monooxygenase; D003545:Cysteine; C034221:catechol