Effects of Tetrahydropterines on the Generation of Quinones Catalyzed by Tyrosinase

Abstract

Tetrahydrobiopterine (6BH 4 ) can diminish the oxidative stress undergone by keratinocytes and melanocytes by reducing the o-quinones generated by the oxidation of the corresponding o-diphenols. We found that 6BH 4 and their analogs reduced all the o-quinones studied. The formal potentials of different quinone/ diphenol pairs indicate that the o-quinones with withdrawing groups are more potent oxidants than those with donating groups.Key words: tetrahydropterines; quinones; o-diphenols;voltammograms; tyrosinaseThe oxidation of diphenols to quinones in keratinocytes and melanocytes involves an increase in oxidative stress in these cells, since H 2 O 2 is generated at the same time.1,2) However, topical applications of formulations containing high concentrations (mM) of coenzyme Q 10 -quinol, hydroquinone (HQ), or estrogens can contribute to increasing oxidative stress in the human epidermis.A reduction in quinones can contribute to decreasing oxidative stress. A possible mechanism for o-quinone reduction is the thioredoxin reductase/thioredoxin (TR/ T) system.3) In human keratinocytes and melanocytes, the presence of the TR isoform has been demonstrated, 4) while 6BH 4 can reduce o-quinone L-dopaquinone back to L-dopa. 5)It has been found that keratinocytes and melanocytes have a capacity for de novo synthesis, recycling, and regulation of 6-tetrahydrobiopterin (6BH 4 ). TR reduces p-quinone 1,4 benzoquinone and coenzyme Q10-quinone back to HQ and coenzyme Q10-quinol. 6) On the other hand, 6BH 4 , can reduce coenzyme Q10-quinone back to coenzyme Q10-quinol, while 1,4 benzoquinone is not reduced to HQ. However, there is controversy concerning the reduction of o-quinones by BH 4 , and it has been proposed that BH 4 does not reduce 1,4 benzoquinone or 1,2 benzoquinone. It has been suggested that the presence of electron-donating subtituents in the quinone structure is needed before reduction by 6BH 4 can occur.6)The objective of this work was to demonstrate that quinones are reduced by 6BH 4 and their analogs MBH 4 (6-methyltetrahydropterin) and DMBH 4 (6,7-dimethyltetrahydropterin). All the o-quinones were assayed, including 1,2-benzoquinone, oxidise BH 4 , and its analogs MBH 4 and DMBH 4 (Scheme 1). In addition we studied the influence of withdrawing and donating groups in C-1 on the redox potential of the o-quinones.First, the formal potentials of the different compounds under study were determined by square wave voltammograms. From these results, it can be seen that the oxidation/reduction potential was greater for compounds (o-quinones) that contained a withdrawing group in C-1 (see below). The potential of p-benzoquinone was near that of BH 4 and its derivatives, which means that they are not oxidised by the quinone.Of the o-diphenols studied, catechol, L-dopa, and 4-tert-butylcatechol (TBC) were easily oxidised by tyrosinase, generating the corresponding o-quinones. In this study, we oxidized them with tyrosinase or with a deficiency of periodate. The results obtained with catechol are shown in Figs. 1 and 2...

Considerations about the kinetic mechanism of tyrosinase in its action on monophenols: A review

“…3). The HHQ derivative that is generated in the passage from EoxHQ to EmHHQ, when released, is oxidized by the oxygen in the medium [38].…”

“…however, years later it was proposed that it was not a substrate for the enzyme [40]. Later it was clearly demonstrated that HQ is a tyrosinase substrate in the presence of hydrogen peroxide, ascorbic acid and with catalytic amounts of TBC [38,41]. This property of HQ may be the origin of its adverse effects, although it has been widely used as a depigmenting agent [42].…”

“…Just as HQ can be oxidized by tyrosinase, it has been suggested that the adverse effects caused by this substrate may be due to the fact that HQ is a tyrosinase substrate [22]. HQ can cause ochronosis [46] and is possibly carcinogenic [47], hence it follows that many of the adverse effects are due to this property [22,38,41,48].…”

“…until recently (see Table 2) [38,41]. The numerical integration of the Scheme 3 mechanism is shown in Fig.…”

Melanogenesis Inhibition Due to NADH

“…The product of the action of TYR on L-tyrosine and L-DOPA (the o-dopaquinone) acts as an oxidant of NADH, since the redox potentials are o-quinone/diphenol = 0.152 V, NAD þ =NADH þ H þ ¼ À0:315 V. 22) This was observed when both TYR activities (diphenolase and monophenolase) were studied in the presence of NADH.…”