Kinetic and solvent isotope effects on biotransformation of aromatic amino acids and their derivatives.
Aromatic amino acids such as l-phenylalanine, l-tryptophan, 3',4'-dihydroxy-l-phenylalanine (l-DOPA), and their derivatives 3',4'-dihydroxyphenylacelaldehyde (DOPAL) and 3',4'-dihydroxyphenylethanol (DOPET), play an essential role in human metabolic processes. Incorrect or slow biotransformation of these compounds leads to some metabolic dysfunctions and in some cases to some neurodegenerative diseases. Therefore, studies of the biotransformation mechanisms of these metabolites draw biochemists' and medical researchers' attention. This study investigates the mechanisms of biotransformation of the aforementioned compounds using kinetic (KIE) and solvent (SIE) isotope effect methods. The overview presents the results and the numerical values of KIE and SIE methods, obtained in the study of biotransformation of l-phenylalanine, 5'-chloro-l-tryptophan, and l-DOPA, catalyzed by the enzymes from the lyases group (phenylalanine ammonia lyase, tryptophan indole-lyase, and tyrosine decarboxylase). Deuterium KIE was also determined during the deamination of 2'-chloro-l-phenylalanine in the presence of the enzyme l-phenylalanine dehydrogenase, as well as in the conversion of DOPAL into DOPET catalyzed by the enzyme alcohol dehydrogenase. The values of KIE and SIE have been determined using a noncompetitive spectrophotometric and a competitive (combined with internal radioactivity standard) radiometric methods.
Department of Biochemistry, Medical University of Warsaw, 2nd Faculty of Medicine, 101 Zwirki i Wigury Av.,, 02-089, Warsaw, Poland.|Department of Chemistry, Warsaw University, 1 Pasteur Str.,, 02-093, Warsaw, Poland.
Marianna
M
Kańska
University of Warsaw, Centre of New Technologies, 2c Banacha Str.,, 02-097, Warsaw, Poland.
Jacek
J
Jemielity
Department of Chemistry, Warsaw University, 1 Pasteur Str.,, 02-093, Warsaw, Poland.
Małgorzata
M
Pająk
Department of Chemistry, Warsaw University, 1 Pasteur Str.,, 02-093, Warsaw, Poland.
Katarzyna
K
Pałka
Department of Biochemistry, Medical University of Warsaw, 2nd Faculty of Medicine, 101 Zwirki i Wigury Av.,, 02-089, Warsaw, Poland.
Katarzyna
K
Podsadni
Department of Chemistry, Warsaw University, 1 Pasteur Str.,, 02-093, Warsaw, Poland.
Elżbieta
E
Winnicka
D024322:Amino Acids, Aromatic / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D007554:Isotopes / Q000737:chemistry; D007700:Kinetics; D011817:Rabbits; D012997:Solvents / Q000737:chemistry*
D024322:Amino Acids, Aromatic; D007554:Isotopes; D012997:Solvents
DOPAL; enzymes; isotope effects; l-DOPA; l-phenylalanine; l-tryptophan