ACTIVITY OF ENZYMES OF TYROSINE METABOLISM IN THE RAT LIVER UNDER THE CONDITIONS OF ACETAMINOPHEN-INDUCED HEPATITIS ON THE BACKGROUND OF PROTEIN DEFICIENCY
DOI:
https://doi.org/10.31861/biosystems2020.01.014Ключові слова:
animal model, protein deficiency, liver, paracetamol, tyrosineАнотація
The contribution of the mis-metabolism of individual amino acids to the development of drug-induced damage to liver cells remains unexplored. The aim of the present study was to investigate the changes in liver tyrosine level and activity of the enzymes of its metabolism: tyrosine aminotransferase, 4-hydroxyphenylpyruvate dioxygenase, aldehyde dehydrogenase ALDH3A1 under the conditions of acetaminophen-induced hepatitis on the background of protein deficiency. Determination of tyrosine in deproteinized with 6% sulfosalicylic acid extracts of the liver tissue was performed using the automatic analyzer of amino acids T-339 (“Microtechnology”, Czech Republic). The enzyme activity was determined by spectrophotometric method – tyrosine aminotransferase by the amount of 4-hydroxybenzaldehyde, which has a maximum absorption at 330 nm, 4-hydroxyphenylpyruvate dioxygenase – by the colored product intensity at λ 336 nm, aldehyde dehydrogenase ALDH3A1 activity was measured at 340 nm wavelength. Results have shown that in animals with toxic liver injury which were maintained in conditions of alimentary protein deficiency, a 5-fold decrease in tyrosine level in the liver was observed. At the same time in animals of this group there was a decrease in TAT activity by 1.6 times, a 4-fold decrease in activity of aldehyde dehydrogenase ALDH3A1 and increase in the activity of 4-hydroxyphenylpyruvate dioxygenase by 2.5 time comparing to control parameters. Conclusion was made, that alimentary protein deficiency is a factor leading to an intensification of tyrosine metabolism disturbances in animals with toxic liver injury. The pronounced exhaustion of the tyrosine pool is accompanied by the activation of the homogentisate pathway of its metabolism, as evidenced by the increase in the
activity of 4-hydroxyphenylpyruvate dioxygenase and simultaneous reduction in the aldehyde dehydrogenase ALDH3A1activity. The established changes open prospects to study the possible targets for the exogenous correction of metabolic disorders under the conditions of intoxication with acetaminophen, especially in people with protein deficiency.
Посилання
Acosta M, Vazquez Fonseca L, Desbats M, et al. Coenzyme Q biosynthesis in health and disease. Biochim Biophys Acta 2016;1857(8):1079-85.
Antonenko A, Blagaia A, Omelchuk S. et al. Mechanism of action of 4-hydroxyphenylpyruvate dioxygenase inhibitor herbicide on homoterm animals and humans. J Pre Clin Clin Res. 2015;9(2):145–150.
Awad A, Bradley M, Fernández-Del-Río L, Nag A, Tsui H, Clarke C. 2018. Coenzyme Q10 deficiencies: pathways in yeast and humans. Essays Biochem 2018;62(3):361-76.
Blind R, Pineda-Torra I, Xu Y, Xu H, Garabedian M. Ligand structural motifs can decouple glucocorticoid receptor transcriptional activation from target promoter occupancy. Biochem Biophys Res Commun 2012;420(4):839-44.
Chernykh A. Aromatic amino acids metabolism in humans exposed to experimental severe acute shortterm normobaric hypoxia. Human Ecology. 2013;7:59- 64.
Cotoia A, Scrima R, Gefter JV, Piccoli C, Cinnella G, et al. p-Hydroxyphenylpyruvate, an Intermediate of the Phe/Tyr Catabolism, Improves Mitochondrial Oxidative Metabolism under Stressing Conditions and Prolongs Survival in Rats Subjected to Profound Hemorrhagic Shock. PLOS ONE. 2014;9(3): e90917.
Dejong CH, van de Poll MC, Soeters PB, Jalan R, Olde Damink SW Aromatic amino acid metabolism during liver failure. J Nutr. 2007;137:1579S-1585S.
Dickson A, Marston F, Pogson C. Tyrosine aminotransferase as the rate-limiting step for tyrosine catabolism in isolated rat liver cells. FEBS Letters 1981;127:28-32.
Granner D, Hargrove J. Regulation of the synthesis of tyrosine aminotransferase: the relationship to mRNATAT. Mol Cell Biochem 1983;53-54(1-2):113- 28.
Jin R, Banton S, Tran T, D., et al. Amino acid metabolism is altered in adolescents with nonalcoholic fatty liver disease – an untargeted, high resolution metabolomics study. J Pediatr 2016;172:14-19.
Kawamukai M. Biosynthesis of coenzyme Q in eukaryotes. Biosci Biotechnol Biochem 2016; 80(1):23- 33.
Knox WE, Pitt BM. Enzymic catalysis of the keto-enol tautomerization of phenylpyruvic acid. J Biol Chem. 1957;225(2):675-88.
Kopylchuk GP, Voloshchuk OM. Peculiarities of the free radical processes in rat liver mitochondria under toxic hepatitis on the background of alimentary protein deficiency. Ukr Biochem J 2016;88(2):66-72. doi: 10.15407/ubj88.02.066. Біологічні системи. Т. 12. Вип. 1. 2020 19
Lee E, Facchini P. Tyrosine aminotransferase contributes to benzylisoquinoline alkaloid biosynthesis in opium poppy. Plant Physiol 2011;157(3):1067-78.
Lee W. Acetaminophen (APAP) hepatotoxicity – Isn’t it time for APAP to go away? J Hepatol 2017;67:1324- 31.
Lowry O, Rosebrough N, Farr A. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-75.
Mehere P, Han Q, Lemkul J. Tyrosine aminotransferase: biochemical and structural properties and molecular dynamics simulations. Protein Cell 2010;1:1023-32.
Mobasher M, Valverde A. Protein tyrosine phosphatase deficiency protects against the induction of the early apoptosis by paracetamol in hepatocytes. An R Acad Nac Farmac 2014;80(4):666-82.
Mukherjee S, Vaidyanathan K, Vasudevan D, Das,S. Role of plasma amino acid and gaba in alcoholic and non-alcoholic liver disease – a pilot study. Indian J Clin Biochem 2010;25(1):37-42.
Nowicka B, Kruk J. Occurrence, biosynthesis and function of isoprenoid quinones. Biochim Biophys Acta 2010;1797(9):1587-605.
Pahari SK, Ghosh S, Halder S, Jana M (2016) Role of Coenzyme Q10 in human life. RJ PT 9(6):635–640.
Panin LE, Usynin IF. Role of glucocorticoids and resident liver macrophages in induction of tyrosine aminotransferase. Biochemistry (Moscow) 2008;73:305-309.
Parajuli B, Fishel M, Hurley T. Selective ALDH3A1 inhibition by benzimidazole analogues increase mafosfamide sensitivity in cancer cells. J Med Chem 2014;57(2):449-61.
Rain-Guion M, Chambon Н. Tyrosine amino transferase as a teaching enzyme in biochemistry class experiment. Biochem Educ 1982;10(3):88-92.
Ramachandran A, Jaeschk H. Mechanisms of acetaminophen hepatotoxicity and their translation to the human pathophysiology. JCTR 2017;3(1):157-69.
Rass IT. Blood content of tyrosine is an index of glucocorticoid action on metabolism. Biochemistry (Mosc). 2010;75(3):353-66.
Reeves P, Nielsen F, Fahey G. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN-76A Rodent. J Nutr. 1993;123(11):1939-51.
Szkopiñska A. Ubiquinone. Biosynthesis of quinone ring and its isoprenoid side chain. Intracellular localization. Acta Biochim Pol 2000;47(2):469-80.
Voloshchuk ON, Kopylchuk GP. The ratio of ubiqiunon redox forms in the liver mitochondria under toxic hepatitis induced on the background of alimentary protein deficiency. Vopr Pitan. 2015;84(5):82-7.
Yoon E, Babar A,Choudhary M, Kutner M, Pyrsopoulos N. Acetaminophen-induced hepatotoxicity: a comprehensive update. JCTH 2016;4(2):131-42