One-electron Oxidation of Biomolecules: Antioxidant Action of DOPA

JAEL NEYRA RECKY; M. LAURA DÁNTOLA; CAROLINA LORENTE

Águas de Lindóia

Congreso; 51th Annual Meeting of the Brazilian Society of Biochemistry and Molecular Biology (SBBq) and 46th Congress of the Brazilian Society of Biophysics (SBBf); 2022

Brazilian Society of Biochemistry and Molecular Biology (SBBq) / Brazilian Society of Biophysics (SBBf)

L-3,4-Dihydroxyphenyl-alanine, known as L-DOPA, is a natural amino acid and the precursor of the neurotransmitters dopamine, norepinephrine, and epinephrine, which are known as catecholamines. It is widely used in the treatment of Parkinson’s  disease, and it has been reported that L-DOPA may prevent H2O2-induced oxidative damage to cellular DNA and LDL oxidation [1,2,3]. Therefore, the objective of our work is to study the antioxidant properties of L-DOPA in photosensitized processes. Photosensitized oxidation of biomolecules occurs due to the absorption of radiation bychromophores that can be endogenous or exogenous. Pterin (Ptr) absorbs UV-A radiation and generates excited states that are harmful to living systems, causing damage to proteins, DNA, and lipids. Although Ptr may photoinduced damage by both type I (electron transfer) and type II (singlet oxygen) mechanisms, type I is the predominant mechanism at physiological pH. Therefore, Ptr triplet excited state and a given biomolecule undergo electron transfer reactions, and the corresponding radicals (Ptr radical anion and a radical cation of the biomolecule, B•+) are formed. In the presence of O2, Ptr is recovered, and the biomolecule is degraded [4]. In our laboratory we have obtained experimental evidence that clearly  demonstrate that the presence of L-DOPA prevents Ptr-photosensitized oxidation of relevant biomolecules. Aqueous solutions containing Ptr and a given amino acid (tyrosine, tryptophan and histidine) or deoxynucleotide (2’deoxyguanosine 5’-monophosphate (dGMP) and  2’deoxyadenosine 5’-monophosphate (dAMP)) were exposed to UV-A radiaton (365 nm), in the absence and in the presence of L-DOPA. For all biomolecules tested was observed a decrease in the rate of consumption proportional to L-DOPA  concentration. A mechanistic analysis indicates that after one-electron transfer with 3Ptr*, all biomolecules studied are recovered in a second one-electron transfer reaction from L-DOPA to B•+. The radical of L-DOPA undergoes further oxidation being a sacrificial antioxidant molecule. [1] Segura-Aguilar J., Paris I., Muñoz P., Ferrari E., Zecca L., Zucca F. A. (2014) J. Neurochem. 129, 898--915. [2] Shia Y. L., Benzieb I. F. F., Buswell J. A. (2002) Life Sci 71, 3047–3057. [3] Exner M., Hermann M., HofbauerR., Kapiotis S, Gmeiner B. M. K. (2003) Free Radical Research 37 (11), 1147–1156. [4] Lorente C., Serrano M. P.,Vignoni M., Dántola M. L., Thomas A. H. (2021) J. Photochem. Photobiol. 7, 100045.