Ukr.Biochem.J. 2020; Volume 92, Issue 1, Jan-Feb, pp. 113-119

doi: https://doi.org/10.15407/ubj92.01.113

Indexes of citrulline metabolism in rat liver under the toxic injury against the background of alimentary protein deficiency

04.02.2020   Uncategorized   No comments

H. P. Kopylchuk, I. M. Nykolaichuk, I. S. Lylyk

Yuriy Fedkovych Chernivtsi National University, Ukraine;
Institute of Biology, Chemistry and Bioresources, Chernivtsi, Ukraine;
e-mail: g.kopilchuk@chnu.edu.ua

Received: 29 May 2019; Accepted: 29 November 2019

It is known that citrulline is converted into arginine in the series of metabolic transformations. Results of our previous studies showed that acetaminophen-induced toxic injury on the background of the alimentary deprivation of protein is accompanied by a decrease in arginine level in rat hepatocytes, but citrulline liver metabolism at these conditions remains incompletely clear. In this work, the content of citrulline in the rat liver mitochondrial and cytosolic fractions and the activity of citrulline-degrading enzymes – argininosuccinate synthase and argininosuccinate lyase were investigated. It was found that in the mitochondrial fraction a maximal reduction of the citrulline levels occurred after administration of acetaminophen toxic doses regardless of the protein amount in the ration, while in the cytosolic fraction the alimentary protein deficiency was a key factor in decreasing the activity of argininosuccinate synthase and arginino-succinate lyase. The data obtained indicated the disturbances of the urea cycle functioning and explained the   decrease of L-arginine level in hepatocytes in conditions of acetaminophen-induced toxic injury against the background alimentary protein deficiency.

Keywords: , , , , ,

References:

  1.  Semba RD. The Rise and Fall of Protein Malnutrition in Global Health. Ann Nutr Metab. 2016;69(2):79-88. PubMed, PubMedCentral, CrossRef
  2. Grover Z, Ee LC. Protein energy malnutrition. Pediatr Clin North Am. 2009;56(5): 1055-1068. PubMed, CrossRef
  3. Kompantsev DV, Popov AV, Privalov IM, Stepanova EF. Protein isolates from vegetable raw materials: an overview of the current state and prospects of development of analysis technology of protein isolates from vegetable raw materials. Modern Probl Sci Educ. 2016;(1). (In Russian). Regime of access : http://www.science-education.ru/ru/article/view?id=24132.
  4.  Agnoli C, Baroni L, Bertini I, Ciappellano S, Fabbri A, Papa M, Pellegrini N, Sbarbati R, Scarino ML, Siani V, Sieri S. Position paper on vegetarian diets from the working group of the Italian Society of Human Nutrition. Nutr Metab Cardiovasc Dis. 2017;27(12):1037-1052. PubMed, CrossRef
  5. Kopylchuk НP, Buchkovska IM, Nikolaev RO. Content of protein fractions of blood plasma in animals under the conditions of protein deficiency. Biological Systems. 2015;7(3):16-20. (In Ukrainian).
  6. Maes M, Vinken M, Jaeschke H. Experimental models of hepatotoxicity related to acute liver failure. Toxicol Appl Pharmacol. 2016;290:86-97. PubMed, PubMedCentral, CrossRef
  7. Ben-Shachar R, Chen Y, Luo S, Hartman C, Reed M, Nijhout HF. The biochemistry of acetaminophen hepatotoxicity and rescue: a mathematical model. Theor Biol Med Model. 2012;9:55.  PubMed, PubMedCentral, CrossRef
  8. Kučera O, Endlicher R, Rychtrmoc D, Lotková H, Sobotka O, Červinková Z. Acetaminophen toxicity in rat and mouse hepatocytes in vitro. Drug Chem Toxicol. 2017;40(4): 448-456.  PubMed, CrossRef
  9.  Kopylchuk НP, Buchkovska IM. The state of the glutathione system of liver cells of rats for low-protein diet and acute hepatotoxic injury. Ukr Biochem J. 2014; 86(5, Suppl 1): 165-166. (In Ukrainian).
  10.  Breuillard C, Cynober L, Moinard C. Citrulline and nitrogen homeostasis: an overview. Amino Acids. 2015;47(4):685-91. PubMed, CrossRef
  11. Kopylchuk HP, Nykolaichuk IM, Zhuretska OM. Rat liver arginase system under acetaminophen-induced toxic injury and protein deprivation. Ukr Biochem J. 2017;89(2):92-98. CrossRef
  12. Bahri S, Zerrouk N, Aussel C, Moinard C, Crenn P, Curis E, Chaumeil JC, Cynober L, Sfar S. Citrulline: from metabolism to therapeutic use. Nutrition. 2013;29(3):479-84. PubMed, CrossRef
  13. Mkhitaryan LS, Kuchmenko OB, Ievstratova IN, Lipkan NG, Vasylynchuk NM, Drobotko TF. Citrulline as a marker of the functional state of organs under pathological conditions. Ukr J Cardiol. 2016;(3):109-115. (In Ukrainian).
  14. Mashiko S, Ishihara A, Iwaasa H, Sano H, Ito J, Gomori A, Oda Z, Moriya R, Matsushita H, Jitsuoka M, Okamoto O, MacNeil DJ, Van der Ploeg LHT, Fukami T, Kanatani A. A pair-feeding study reveals that a Y5 antagonist causes weight loss in diet-induced obese mice by modulating food intake and energy expenditure. Mol Pharmacol. 2007;71(2):602-8. PubMed, CrossRef
  15. Reeves PG, Nielsen FH, Fahey GCJr. 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 diet. J Nutr. 1993;123(11):1939-51. PubMed, CrossRef
  16. Stefanov OV. Preclinical studies of drugs. Kyiv: Avicenna, 2001. 527 p. (In Ukrainian).
  17. Kopylchuk GP, Voloshchuk OM. NADH:ubiquinone reductase and succinate dehydrogenase activity in the liver of rats with acetaminopheninduced toxic hepatitis on the background of alimentary protein deficiency. Ukr Biochem J. 2015; 87(1):121-126. (In Ukrainian). PubMed, CrossRef
  18.  Marchenko МM, Kopylchuk GP, Shmarakov IO, Buchkovska IM. Activity of enzymatic detoxification systems in the mice liver under conditions of different retinoid provision. Ukr Biokhim Zhurn. 2012 Mar-Apr;84(2):42-7. (In Ukrainian). PubMed
  19.  Ratner S, Pappas A. Biosynthesis of urea; enzymatic mechanism of arginine synthesis from citrulline. J Biol Chem. 1949;179(3):1183-1198. PubMed
  20.  Archibald RM. Determination of citrulline and allantoin and demonstration of citrulline in blood plasma. J Biol Chem. 1944;156:121-142.
  21. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1): 265-75. PubMed
  22. Indiveri C, Tonazzi A, De Palma A., Palmieri F. Kinetic mechanism of anti-ports catalyzed by reconstituted ornithine/citrulline carrier from rat liver mitochondria. Biochim Biophys Acta. 2001;1503(3): 303-313.  PubMed, CrossRef
  23.  Giangregorio N, Tonazzi A,Console L, Galluccio M, Porcelli V, Indiveri C.  Structure/function relationships of the human mitochondrial ornithine/citrulline carrier by cys site-directed mutagenesis. Relevance to mercury toxicity. Int J Biol Macromol. 2018;120(Pt A):93-99.  PubMed, CrossRef
  24.  Van de Poll MCG, Siroen MPC, van Leeuwen PAM, Soeters PB, Melis GC, Boelens PG, Deutz NEP, Dejong CHC. Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism. Am J Clin Nutr. 2007;85(1):167-72. PubMed, CrossRef
  25. Neis EPJG, Sabrkhany S, Hundscheid I, Schellekens D, Lenaerts K, Olde Damink SW, Blaak EE, Dejong CHC, Rensen SS. Human splanchnic amino-acid metabolism. Amino Acids. 2017;49(1):161-172. PubMed, PubMedCentral, CrossRef
  26.  Moinard C, Cynober L. Citrulline: a new player in the control of nitrogen ho-meostasis. J Nutr. 2007;137(6 Suppl 2): 1621S-1625S.  PubMed, CrossRef
  27.  Ivanovski I, Ješić M, Ivanovski A, Garavelli L, Ivanovski P. Metabolically based liver damage pathophysiology in patients with urea cycle disorders – A new hypothesis. World J Gastroenterol. 2017;23(44):7930-7938. PubMed, PubMedCentral, CrossRef
  28.  Saheki T, Kobayashi K. Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD). J Hum Genet. 2002; 47(7): 333-341. PubMed, CrossRef
  29.  Voloshchuk ON, Kopylchuk GP. The State of the Adenyl Nucleotide System in the Liver of Rats with Toxic Hepatitis under Conditions of Protein Deficiency. Biophysics. 2017; 62(6): 980-983. CrossRef
  30.  Voloshchuk ON, Kopylchuk GP, Badyak OD. Activity of the liver malate-aspartate shuttle mitochondrial enzymes in rats under the conditions of alimentary deficiency of protein. J Fundam Med Biol. 2015;(2):33-37. (In Russian).
  31. Lanpher B, Brunetti-Pierri N, Lee B. Inborn Errors of Metabolism: The Flux From Mendelian to Complex Diseases. Nat Rev Genet. 2006;7(6):449-460.  PubMed, CrossRef
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