1. Study of tyrosine and dopa enantiomers as tyrosinase substrates initiating l- and d-melanogenesis pathways
Pedro J Fernandez-Julia, Francisco Garcia-Canovas, Jose Tudela-Serrano, Jose L Munoz-Munoz, Francisco Garcia-Molina, Antonia Garcia-Jimenez Biotechnol Appl Biochem . 2021 Aug;68(4):823-831. doi: 10.1002/bab.1998.
Tyrosinase starts melanogenesis and determines its course, catalyzing the oxidation by molecular oxygen of tyrosine to dopa, and that of dopa to dopaquinone. Then, nonenzymatic coupling reactions lead to dopachrome, which evolves toward melanin. Recently, it has been reported that d-tyrosine acts as tyrosinase inhibitor and depigmenting agent. The action of tyrosinase on the enantiomers of tyrosine (l-tyrosine and d-tyrosine) and dopa (l-dopa and d-dopa) was studied for the first time focusing on quantitative transient phase kinetics. Post-steady-state transient phase studies revealed that l-dopachrome is formed more rapidly than d-dopachrome. This is due to the lower values of Michaelis constants for l-enantiomers than for d-enantiomers, although the maximum rates are equal for both enantiomers. A deeper analysis of the inter-steady-state transient phase of monophenols demonstrated that the enantiomer d-tyrosine causes a longer lag period and a lower steady-state rate, than l-tyrosine at the same concentration. Therefore, d-melanogenesis from d-tyrosine occurs more slowly than does l-melanogenesis from l-tyrosine, which suggests the apparent inhibition of melanin biosynthesis by d-tyrosine. As conclusion, d-tyrosine acts as a real substrate of tyrosinase, with low catalytic efficiency and, therefore, delays the formation of d-melanin.
2. Heat Capacities of l-Histidine, l-Phenylalanine, l-Proline, l-Tryptophan and l-Tyrosine
Michal Fulem, Václav Pokorný, Květoslav Růžička, Vojtěch Štejfa, Jakub Havlín Molecules . 2021 Jul 15;26(14):4298. doi: 10.3390/molecules26144298.
In an effort to establish reliable thermodynamic data for proteinogenic amino acids, heat capacities for l-histidine (CAS RN: 71-00-1), l-phenylalanine (CAS RN: 63-91-2), l-proline (CAS RN: 147-85-3), l-tryptophan (CAS RN: 73-22-3), and l-tyrosine (CAS RN: 60-18-4) were measured over a wide temperature range. Prior to heat capacity measurements, thermogravimetric analysis was performed to determine the decomposition temperatures while X-ray powder diffraction (XRPD) and heat-flux differential scanning calorimetry (DSC) were used to identify the initial crystal structures and their possible transformations. Crystal heat capacities of all five amino acids were measured by Tian-Calvet calorimetry in the temperature interval from 262 to 358 K and by power compensation DSC in the temperature interval from 307 to 437 K. Experimental values determined in this work were then combined with the literature data obtained by adiabatic calorimetry. Low temperature heat capacities of l-histidine, for which no literature data were available, were determined in this work using the relaxation (heat pulse) calorimetry from 2 K. As a result, isobaric crystal heat capacities and standard thermodynamic functions up to 430 K for all five crystalline amino acids were developed.
3. O-(2-[18F]-Fluoroethyl)-L-Tyrosine (FET) in Neurooncology: A Review of Experimental Results
Carina Stegmayr, Antje Willuweit, Karl-Josef Langen, Philipp Lohmann Curr Radiopharm . 2019;12(3):201-210. doi: 10.2174/1874471012666190111111046.
In recent years, PET using radiolabelled amino acids has gained considerable interest as an additional tool besides MRI to improve the diagnosis of cerebral gliomas and brain metastases. A very successful tracer in this field is O-(2-[18F]fluoroethyl)-L-tyrosine (FET) which in recent years has replaced short-lived tracers such as [11C]-methyl-L-methionine in many neuro-oncological centers in Western Europe. FET can be produced with high efficiency and distributed in a satellite concept like 2- [18F]fluoro-2-deoxy-D-glucose. Many clinical studies have demonstrated that FET PET provides important diagnostic information regarding the delineation of cerebral gliomas for therapy planning, an improved differentiation of tumor recurrence from treatment-related changes and sensitive treatment monitoring. In parallel, a considerable number of experimental studies have investigated the uptake mechanisms of FET on the cellular level and the behavior of the tracer in various benign lesions in order to clarify the specificity of FET uptake for tumor tissue. Further studies have explored the effects of treatment related tissue alterations on tracer uptake such as surgery, radiation and drug therapy. Finally, the role of blood-brain barrier integrity for FET uptake which presents an important aspect for PET tracers targeting neoplastic lesions in the brain has been investigated in several studies. Based on a literature research regarding experimental FET studies and corresponding clinical applications this article summarizes the knowledge on the uptake behavior of FET, which has been collected in more than 30 experimental studies during the last two decades and discusses the role of these results in the clinical context.
