59-92-7Relevant articles and documents
New L-dopa codrugs as potential antiparkinson agents
Sozio, Piera,Iannitelli, Antonio,Cerasa, Laura Serafina,Cacciatore, Ivana,Cornacchia, Catia,Giorgioni, Gianfabio,Ricciutelli, Massimo,Nasuti, Cinzia,Cantalamessa, Franco,Di Stefano, Antonio
, p. 412 - 417 (2008)
This paper reports the synthesis and preliminary evaluation of new L-dopa (LD) conjugates (1 and 2) obtained by joining LD with two different natural antioxidants, caffeic acid and carnosine, respectively. The antioxidant efficacy of compounds 1 and 2 was
Detection of tyrosine and monitoring tyrosinase activity using an enzyme cascade-triggered colorimetric reaction
Chen, Huei-Yu,Yeh, Yi-Chun
, p. 29745 - 29750 (2020)
The aromatic amino acid tyrosine is an essential precursor for the synthesis of catecholamines, including l-DOPA, tyramine, and dopamine. A number of metabolic disorders have been linked to abnormal tyrosine levels in biological fluids. In this study, we developed an enzyme cascade-triggered colorimetric reaction for the detection of tyrosine, based on the formation of yellow pigment (betalamic acid) and red fluorometric betaxanthin. Tyrosinase converts tyrosine to l-DOPA, and DOPA-dioxygenase catalyzes oxidative cleavage of l-DOPA into betalamic acid. Response is linear for tyrosine from 5 to 100 μM, and the detection limit (LOD) is 2.74 μM. The enzyme cascade reaction was applied to monitor tyrosinase activity and tyrosinase inhibition assays. Lastly, the performance of the proposed biosensor proved successful in the analysis of urine samples without the need for pre-treatment. This journal is
Immobilization of polyphenol oxidase onto mesoporous activated carbons - isotherm and kinetic studies
John Kennedy,Selvi,Aruna Padmanabhan,Hema,Sekaran
, p. 262 - 270 (2007)
Investigations were carried out in batch modes for studying the immobilization behavior of polyphenol oxidase (PPO) on two different mesoporous activated carbon matrices, MAC400 and MAC200. The PPO was immobilized onto MAC400 and MAC200 at various enzyme activities 5 × 104, 10 × 104, 20 × 104, 30 × 104 U l-1, at pH 5-8, and at temperature ranging from 10 to 40 °C. The intensity of immobilization of PPO increased with increase in temperature and initial activities, while it decreased with increase in pH. Immobilization onto MAC400 followed the Langmuir model while Langmuir and Freundlich models could fit MAC200 data. Non-linear pseudo first order, pseudo second order and intraparticle diffusion models were evaluated to understand the mechanism of immobilization. The free and immobilized enzyme kinetic parameters (Km and Vmax) were determined by Michaelis-Menten enzyme kinetics. The Km values for free enzyme, PPO immobilized in MAC400 and in MAC200 were 0.49, 0.41 and 0.65 mM, respectively. The immobilization of PPO in carbon matrices was confirmed using FT-IR spectroscopy and scanning electron microscopy.
Measurement of intrinsic rate constants in the tyrosine hydroxylase reaction
Eser, Bekir E.,Fitzpatrick, Paul F.
, p. 645 - 652 (2010)
Tyrosine hydroxylase (TyrH) is a pterin-dependent mononuclear non-heme aromatic amino acid hydroxylase that catalyzes the conversion of tyrosine to dihydroxyphenylalanine (DOPA). Chemical quench analyses of the enzymatic reaction show a burst of DOPA formation, followed by a linear rate equal to the kcat value at both 5 and 30 °C. The effects of increasing solvent viscosity confirm that kcat is ～84% limited by diffusion, most probably due to slow product release, and that tyrosine has a commitment to catalysis of 0.45. The effect of viscosity on the kcat/Km for 6-methyltetrahydropterin is greater than the theoretical limit, consistent with the coupling of pterin binding to the movement of a surface loop. The absorbance changes in the spectrum of the tetrahydropterin during the first turnover, the kinetics of DOPA formation during the first turnover, and the previously described kinetics for formation and decay of the Fe(IV)O intermediate [Eser, B. E., Barr, E. W., Frantom, P. A., Saleh, L., Bollinger, J. M., Jr., Krebs, C., and Fitzpatrick, P. F. (2007) J. Am. Chem. Soc. 129, 11334-11335] were analyzed globally, yielding a single set of rate constants for the TyrH reaction. Reversible binding of oxygen is followed by formation of Fe(IV)O and 4a-hydroxypterin with a rate constant of 13 s-1 at 5 °C. Transfer of oxygen from Fe(IV)O to tyrosine to form DOPA follows with a rate constant of 22 s-1. Release of DOPA and/or the 4a-hydroxypterin with a rate constant of 0.86 s-1 completes the turnover.
Reductase-catalyzed tetrahydrobiopterin regeneration alleviates the anti-competitive inhibition of tyrosine hydroxylation by 7,8-dihydrobiopterin
Ding, Zhongyang,Li, Leyun,Li, Youran,Shi, Guiyang,Xu, Yinbiao,Zhang, Liang
, p. 3128 - 3140 (2021)
l-Tyrosine hydroxylation by tyrosine hydroxylase is a significant reaction for preparing many nutraceutical and pharmaceutical chemicals. Two major challenges in constructing these pathways in bacteria are the improvement of hydroxylase catalytic efficiency and the production of cofactor tetrahydrobiopterin (BH4). In this study, we analyzed the evolutionary relationships and conserved protein sequences between tyrosine hydroxylases from different species by PhyML and MAFFT. Finally, we selected 7 tyrosine hydroxylases and 6 sepiapterin reductases. Subsequently, the function of different groups was identified by a combined whole-cell catalyst, and a series of novel tyrosine hydroxylase/sepiapterin reductase (TH/SPR) synthesis systems were screened including tyrosine hydroxylase (from Streptosporangium roseum DSM 43021 and Thermomonospora curvata DSM 43183) and sepiapterin reductase (from Photobacterium damselae, Chlorobaculum thiosulfatiphilum and Xenorhabdus poinarii), namely as SrTH/PdSPR, SrTH/CtSPR, SrTH/XpSPR and TcTH/PdSPR, which can synthesize l-Dopa by hydroxylating l-tyrosine in Bacillus licheniformis. Furthermore, we analyzed the characterization of SrTH by enzyme catalysis and demonstrated that 7,8-dihydrobiopterin (BH2) formed by BH4 autooxidation was an anticompetitive inhibitor on SrTH. Finally, pure dihydropteridine reductase from Escherichia coli (EcDHPR) was added to the solution, and l-Dopa could be continually synthesized after 3 h, which was improved by 86% at 6 h in the catalytic reaction by SrTH. This indicates that BH4 regeneration can alleviate the inhibition by BH2 during tyrosine hydroxylation. This study provides a good starting point and theoretical foundation for further modification to improve the catalytic efficiency of tyrosine hydroxylation by tyrosine hydroxylase.
Novel strategy for enhancing productivity in l-DOPA synthesis: The electroenzymatic approach using well-dispersed l-tyrosine
Min, Kyoungseon,Kathavarayan, Thenmozhi,Park, Kyungmoon,Yoo, Young Je
, p. 87 - 90 (2013)
Although l-DOPA (l-3,4-dihydroxyphenylalanine) is widely used as a drug for Parkinson's disease, there are critical drawbacks in the commercial synthetic method such as low conversion rate, poor productivity, and long operational time. In order to overcome these limitations, a novel electroenzymatic system using tyrosinase/carbon nanopowder/polypyrrole composite as a working cathode was reported with the outstanding conversion rate up to 95.9%. However, the productivity was still limited due to a low solubility of the substrate l-tyrosine in aqueous phase. Herein, we demonstrated a novel strategy for enhancing the productivity by employing well-dispersed l-tyrosine as the substrate. When using well-dispersed l-tyrosine, not only the concentration of the substrate was increased to 90.6 gL-1 in aqueous phase but also the productivity was enhanced up to 15.3 gL-1 h-1. We also determined kinetic parameters in the electroenzymatic system and the kinetic results revealed that the outstanding conversion rate was based on the fast electrical reduction of the by-product to l-DOPA. Thus the electroenzymatic synthesis using well-dispersed l-tyrosine can be a potential candidate as a novel process for l-DOPA synthesis.
Histidine residues at the copper-binding site in human tyrosinase are essential for its catalytic activities
Choi, Hye Won,Hong, Sungguan,Jo, Hyun-Joo,Kong, Kwang-Hoon,Lee, Sung Jun,Noh, Hyangsoon
, p. 726 - 732 (2020)
Tyrosinase is a copper-binding enzyme involved in melanin biosynthesis. However, the detailed structure of human tyrosinase has not yet been solved, along with the identification of the key sites responsible for its catalytic activity. We used site-directed mutagenesis to identify the residues critical for the copper binding of human tyrosinase. Seven histidine mutants in the two copper-binding sites were generated, and catalytic activities were characterised. The tyrosine hydroxylase activities of the CuA site mutants were approximately 50% lower than those of the wild-type tyrosinase, while the dopa oxidation activities of the mutants were not significantly different from that of wild-type tyrosinase. By contrast, mutations at CuB significantly decreased both tyrosine hydroxylation and dopa oxidation activities, confirming that the catalytic sites for these two activities are at least partially distinct. These findings provide a useful resource for further structural determination and development of tyrosinase inhibitors in the cosmetic and pharmaceutical industries.
Daedalin A, a metabolite of daedalea dickinsii, inhibits melanin synthesis in an in vitro human skin model
Morimura, Keiji,Hiramatsu, Kenji,Yamazaki, Chihiro,Hattori, Yasunao,Makabe, Hidefumi,Hirota, Mitsuru
, p. 627 - 632 (2009)
The culture broth of Daedalea dickinsii was found to predominantly contain the tyrosinase inhibitor, (2R)-6- hydroxy-2-hydroxymethyl-2-methyl-2H-chromene, daedalin A (1). Ongoing research into bioactive metabolites resulted in the identification of two new 2H-chromenes, 6-hydroxy-5,7-dimethoxy-2,2-dimethyl-2H- chromene (3) and 6-hydroxy-2-hydroxymethyl-5-methoxy-2-methyl- 2H-chromene (4), together with 6-hydroxy-2,2-dimethyl- 2H-chromene (2). Comparative studies of isolated compounds 1-4 and related compounds (±)-1 and 1a-1c showed 1 to have the strongest tyrosinase inhibitory activity. These results suggest that the hydroxyl groups at positions 6 and 9 of 1 were important for the potent activity. A Lineweaver-Burk plot for a kinetic analysis indicates that 1 competed with L-tyrosine for tyrosinase. Compound 1 also suppressed melanogenesis in a human skin model (up to 49% at 2.8μmol/tissue application) without affecting the cell viability. Compounds 1, 1b and 1c also showed 1,1- diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity comparable to that of α-tocopherol.
Singlet oxygen-mediated protein oxidation: Evidence for the formation of reactive side chain peroxides on tyrosine residues
Wright, Adam,Bubb, William A.,Hawkins, Clare L.,Davies, Michael J.
, p. 35 - 46 (2002)
Singlet oxygen (1O2) is generated by a number of enzymes as well as by UV or visible light in the presence of a sensitizer and has been proposed as a damaging agent in a number of pathologies including cataract, sunburn, and skin can
Pulsed EPR study of amino acid and tetrahydropterin binding in a tyrosine hydroxylase nitric oxide complex: Evidence for substrate rearrangements in the formation of the oxygen-reactive complex
Krzyaniak, Matthew D.,Eser, Bekir E.,Ellis, Holly R.,Fitzpatrick, Paul F.,McCracken, John
, p. 8430 - 8441 (2013)
Tyrosine hydroxylase is a nonheme iron enzyme found in the nervous system that catalyzes the hydroxylation of tyrosine to form l-3,4- dihydroxyphenylalanine, the rate-limiting step in the biosynthesis of the catecholamine neurotransmitters. Catalysis requires the binding of three substrates: tyrosine, tetrahydrobiopterin, and molecular oxygen. We have used nitric oxide as an O2 surrogate to poise Fe(II) at the catalytic site in an S = 3/2, {FeNO}7 form amenable to EPR spectroscopy. 2H-electron spin echo envelope modulation was then used to measure the distance and orientation of specifically deuterated substrate tyrosine and cofactor 6-methyltetrahydropterin with respect to the magnetic axes of the {FeNO}7 paramagnetic center. Our results show that the addition of tyrosine triggers a conformational change in the enzyme that reduces the distance from the {FeNO}7 center to the closest deuteron on 6,7-2H-6-methyltetrahydropterin from >5.9 A to 4.4 ± 0.2 A. Conversely, the addition of 6-methyltetrahydropterin to enzyme samples treated with 3,5-2H-tyrosine resulted in reorientation of the magnetic axes of the S = 3/2, {FeNO}7 center with respect to the deuterated substrate. Taken together, these results show that the coordination of both substrate and cofactor direct the coordination of NO to Fe(II) at the active site. Parallel studies of a quaternary complex of an uncoupled tyrosine hydroxylase variant, E332A, show no change in the hyperfine coupling to substrate tyrosine and cofactor 6-methyltetrahydropterin. Our results are discussed in the context of previous spectroscopic and X-ray crystallographic studies done on tyrosine hydroxylase and phenylalanine hydroxylase.
