Novel Biosynthesis, Metabolism and Physiological Functions of L-Homoarginine

Author(s): Seidu Adams*, Dongsheng Che*, Guixin Qin, Mohammed Hamdy Farouk, Jiang Hailong, Han Rui.

Journal Name: Current Protein & Peptide Science

Volume 20 , Issue 2 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

L-Homoarginine (hArg) ((2S)-amino-6-Carbamimidamidohexanoic acid) is a non-essential cationic amino acid that may be synthesised from the lysine catabolism or the transamination of its precursor (Arginine: Arg). These processes involve the use of the ornithine transcarbamoylase (OTC), an enzyme from the urea cycle or the arginine: glycine amidinotransferase (AGAT), an enzyme from the creatine biosynthesis pathway. These enzymes are tissue-specific, hence they synthesised L-hArg in animals and human organs such as the liver, kidneys, brains, and the small intestines. L-hArg plays some important roles in the pathophysiological conditions, endothelial functions, and the energy metabolic processes in different organs. These functions depend on the concentrations of the available LhArg in the body. These different concentrations of the L-hArg in the body are related to the different disease conditions such as the T2D mellitus, the cardiovascular and the cerebrovascular diseases, the chronic kidney diseases, the intrauterine growth restriction (IUGR) and the preeclampsia (PE) in pregnancy disorders, and even mortality. However, the applications of the L-hArg in both human and animal studies is in its juvenile stage, and the mechanism of action in this vital amino acid is not fully substantiated and requires more research attention. Hence, we review the evidence with the perspective of the LhArg usage in the monogastric and human nutrition and its related health implications.

Keywords: L-Homoarginine, nitric oxide, AGAT, OTC, cardiovascular diseases, metabolism.

[1]
Tsikas, D.; Wu, G. Homoarginine, arginine, and relatives: Analysis, metabolism, transport, physiology, and pathology. Amino Acids, 2015, 47(9), 1697-1702.
[2]
Rutherfurd, S.M. Use of the guanidination reaction for determining reactive lysine, bioavailable lysine and gut endogenous lysine. Amino Acids, 2015, 47(9), 1805-1815.
[3]
Yin, J.; Ren, W.; Hou, Y.; Wu, M.; Xiao, H.; Duan, J.; Zhao, Y.; Li, T.; Yin, Y.; Wu, G.; Nyachoti, C.M. Use of homoarginine for measuring true ileal digestibility of amino acids in food protein. Amino Acids, 2015, 47(9), 1795-1803.
[4]
Valtonen, P.; Laitinen, T.; Lyyra, L.T.; Raitakari, O.T.; Juonala, M.; Viikari, J.S.A.; Heiskanen, N.; Vanninen, E.; Punnonen, K.; Heinonen, S. Serum l-homoarginine concentration is elevated during normal pregnancy and is related to flow-mediated vasodilatation. Circulation, 2008, 72(11), 1879-1884.
[5]
Tommasi, S.; Elliot, D.J.; Da Boit, M.; Gray, S.R.; Lewis, B.C.; Mangoni, A.A. Homoarginine and inhibition of human arginase activity: kinetic characterization and biological relevance. Sci. Rep., 2018, 8(1), 3697.
[6]
Berüter, J.; Colombo, J.P.; Bachmann, C. Purifcation and properties of arginase from human liver and erythrocytes. J. Acad. Gen. Dent., 1978, 175, 449-454.
[7]
Ikemoto, M.; Tabata, M.; Miyake, T.; Kono, T.; Mori, M.; Totani, M.; Murachi, T. Expression of human liver arginase in Escherichia coli. Purification and properties of the product. Biochem. J., 1990, 270(3), 697.
[8]
Hrabak, A.; Bajor, T.; Temesi, A. Comparison of Substrate and inhibitor specifcity of arginase and nitricm oxide (NO) synthase for arginine analogs and related compounds in murine and rat macrophages. Biochem. Biophys. Res. Commun., 1994, 198, 206-212.
[9]
Blachier, F.; Mourtada, A.; Sener, A.; Malaisse, W.J. Stimulus-secretion coupling of arginine-induced insulin release. Uptake of metabolized and nonmetabolized cationic amino acids by pancreatic islets. Endocrinology, 1989, 124(1), 134-141.
[10]
Radomski, M.W.; Palmer, R.M.; Moncada, S. An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc. Natl. Acad. Sci. USA, 1990, 87(13), 5193-5197.
[11]
Drechsler, C.; Pihlstrom, H.; Meinitzer, A.; Pilz, S.; Tomaschitz, A.; Abedini, S.; Fellstrom, B.; Jardine, A.G.; Wanner, C.; Marz, W.; Holdaas, H. Homoarginine and clinical outcomes in renal transplant recipients: Results from the assessment of lescol in renal transplantation study. Transplantation, 2015, 99(7), 1470-1476.
[12]
Atzler, D.; McAndrew, D.J.; Cordts, K.; Schneider, J.E.; Zervou, S.; Schwedhelm, E.; Neubauer, S.; Lygate, C.A. Dietary supplementation with homoarginine preserves cardiac function in a murine model of post-myocardial infarction heart failure. Circulation, 2017, 135(4), 400-402.
[13]
Kim, S.; Thiessen, P.A.; Bolton, E.E.; Chen, J.; Fu, G.; Gindulyte, A.; Han, L.; He, S.H.; Shoemaker, B.A. PubChem substance and compound databases. Nucleic Acids Res., 2015, 44(D1), D1202-D1213.
[14]
Suzuki, H.; Ishii, J.; Kondo, A.; Yoshida, K. Polyamino acid display on cell surfaces enhances salt and alcohol tolerance of Escherichia coli. Biotechnol. Lett., 2015, 37(2), 429-435.
[15]
Gu, Z.Y.; Liu, Y.; Wang, F.; Bao, X.; Wang, S.Y.; Ji, S.J. Cobalt(II)-catalyzed synthesis of sulfonyl guanidines via nitrene radical coupling with isonitriles: A combined experimental and computational study. ACS Catal., 2017, 7(6), 3893-3899.
[16]
Tews, J.K.; Harper, A.E. Induction in rats of lysine imbalance by dietary homoarginine. J. Nutr., 1986, 116(10), 1910-1921.
[17]
Angkanaporn, K.; Ravindran, V.; Bryden, W.L. De novo synthesis of homoarginine in chickens is influenced by dietary concentrations of lysine and arginine. Nutr. Res., 1997, 17(1), 99-110.
[18]
Tews, J.K.; Harper, A.E. Tissue amino acids in rats fed norleucine, norvaline, homoarginine or other amino acid analogues. J. Nutr., 1986, 116(8), 1464-1472.
[19]
Wu, G. Amino acids. Biochemistry and Nutrition. 2013, NW: Taylor Francis.
[20]
Schmitz, M.; Hagemeister, H.; Erbersdobler, H.F. Homoarginine labeling is suitable for determination of protein absorption in miniature pigs. J. Nutr., 1991, 121(10), 1575-1580.
[21]
Monne, M.; Miniero, D.V.; Daddabbo, L.; Palmieri, L.; Porcelli, V.; Palmieri, F. Mitochondrial transporters for ornithine and related amino acids: A review. Amino Acids, 2015, 47(9), 1763-1777.
[22]
May, M.; Kayacelebi, A.A.; Batkai, S.; Jordan, J.; Tsikas, D.; Engeli, S. Plasma and tissue homoarginine concentrations in healthy and obese humans. Amino Acids, 2015, 47(9), 1847-1852.
[23]
Hara, H.; Nishi, T.; Kasai, T. A protein less sensitive to trypsin, guanidinated casein, is a potent stimulator of exocrine pancreas in rats. Proc. Soc. Exp. Biol. Med., 1995, 210(3), 278-284.
[24]
Hira, T.; Ohyama, S.; Hara, H. L-homoarginine suppresses exocrine pancreas in rats. Amino Acids, 2003, 24(4), 389-396.
[25]
Frenay, A.R.; Kayacelebi, A.A.; Beckmann, B.; Soedamah-Muhtu, S.S.; de Borst, M.H.; van den Berg, E.; van Goor, H.; Bakker, S.J.; Tsikas, D. High urinary homoarginine excretion is associated with low rates of all-cause mortality and graft failure in renal transplant recipients. Amino Acids, 2015, 47(9), 1827-1836.
[26]
Hou, Y.; Jia, S.; Nawaratna, G.; Hu, S.; Dahanayaka, S.; Bazer, F.W.; Wu, G. Analysis of l-homoarginine in biological samples by HPLC involving precolumn derivatization with o-phthalaldehyde and N-acetyl-l-cysteine. Amino Acids, 2015, 47(9), 2005-2014.
[27]
Pilz, S.; Meinitzer, A.; Gaksch, M.; Grubler, M.; Verheyen, N.; Drechsler, C.; Hartaigh, B.O.; Lang, F.; Alesutan, I.; Voelkl, J.; Marz, W.; Tomaschitz, A. Homoarginine in the renal and cardiovascular systems. Amino Acids, 2015, 47(9), 1703-1713.
[28]
Bernstein, H.G.; Jager, K.; Dobrowolny, H.; Steiner, J.; Keilhoff, G.; Bogerts, B.; Laube, G. Possible sources and functions of l-homoarginine in the brain: Review of the literature and own findings. Amino Acids, 2015, 47(9), 1729-1740.
[29]
Ryan, W.L.; Barak, A.J.; Johnson, R.J. Lysine, homocitrulline, and homoarginine metabolism by the isolated perfused rat liver. Arch. Biochem. Biophys., 1968, 123(2), 294-297.
[30]
Ryan, W.L.; Johnson, R.J.; Dimari, S. Homoarginine synthesis by rat kidney. Arch. Biochem. Biophys., 1969, 131(2), 521-526.
[31]
Wyss, M.; Kaddurah-Daouk, R. Creatine and creatinine metabolism. Physiol. Rev., 2000, 80(3), 1107-1213.
[32]
Choe, C.U.; Nabuurs, C.; Stockebrand, M.C.; Neu, A.; Nunes, P.; Morellini, F.; Sauter, K.; Schillemeit, S.; Hermans-Borgmeyer, I.; Marescau, B.; Heerschap, A.; Isbrandt, D. L-arginine: Glycine amidinotransferase deficiency protects from metabolic syndrome. Hum. Mol. Genet., 2013, 22(1), 110-123.
[33]
Cathelineau, L.; Saudubray, J.M.; Charpentier, C.; Polonovski, C. Letter: The presence of the homoanalogues of substrates of the urea cycle in the presence of argininosuccinate synthetase deficiency. Pediatr. Res., 1974, 8, 857.
[34]
Levin, B.; Oberholzer, V.G.; Palmer, T. Letter: The high levels of lysine, homocitrulline, and homoarginine found in argininosuccinate synthetase deficiency. Pediatr. Res., 1974, 8, 857-858.
[35]
Hunter, A.; Downs, C.E. The inhibition of arginase by amino acids. J. Biol. Chem., 1945, 157, 427-446.
[36]
Reczkowski, R.S.; Ash, D.E. Rat liver arginase: kinetic mechanism, alternate substrates, and inhibitors. Arch. Biochem. Biophys., 1994, 312(1), 31-37.
[37]
Cullen, M.E.; Yuen, A.H.Y.; Felkin, L.E.; Smolenski, R.T.; Hall, J.L.; Grindle, S.; Miller, L.W.; Birks, E.J.; Yacoub, M.H.; Barton, P.J.R. Myocardial expression of the arginine: Glycine amidinotransferase gene is elevated in heart failure and normalized after recovery: Potential implications for local creatine synthesis. Circulation, 2006, 114(1), 16-20.
[38]
Hernandez, G.G.; Alvarez, M.A. Isolation and characterization of the gene coding for the amidinotransferase involved in the biosynthesis of phaseolotoxin in Pseudomonas syringae pv. phaseolicola. Inter. Soc. Mol. Plant Microbe Interact., 2001, 14(4), 545-554.
[39]
Kato, T.; Sano, M.; Mizutani, N.; Hayakawa, C. Homocitrullinuria and homoargininuria in hyperargininaemia. J. Inherit. Metab. Dis., 1988, 11(3), 261-265.
[40]
Maestri, N.E.; Brusilow, S.W.; Clissold, D.B.; Bassett, S.S. Long-term treatment of girls with ornithine transcarbamylase deficiency. N. Engl. J. Med., 1996, 335(12), 855-860.
[41]
Davids, M.; Ndika, J.D.; Salomons, G.S.; Blom, H.J.; Teerlink, T. Promiscuous activity of arginine: Glycine amidinotransferase is responsible for the synthesis of the novel cardiovascular risk factor homoarginine. FEBS Lett., 2012, 586(20), 3653-3657.
[42]
Choe, C.U.; Atzler, D.; Wild, P.S.; Carter, A.M.; Boger, R.H.; Ojeda, F.; Simova, O.; Stockebrand, M.; Lackner, K.; Nabuurs, C.; Marescau, B.; Streichert, T.; Muller, C.; Luneburg, N.; De Deyn, P.P.; Benndorf, R.A.; Baldus, S.; Gerloff, C.; Blankenberg, S.; Heerschap, A.; Grant, P.J.; Magnus, T.; Zeller, T.; Isbrandt, D.; Schwedhelm, E. Homoarginine levels are regulated by l-arginine: Glycine amidinotransferase and affect stroke outcome: Results from human and murine studies. Circulation, 2013, 128(13), 1451-1461.
[43]
Kayacelebi, A.A.; Langen, J.; Weigt-Usinger, K.; Chobanyan-Jurgens, K.; Mariotti, F.; Schneider, J.Y.; Rothmann, S.; Frolich, J.C.; Atzler, D.; Choe, C.U.; Schwedhelm, E.; Huneau, J.F.; Lucke, T.; Tsikas, D. Biosynthesis of homoarginine (hArg) and asymmetric dimethylarginine (ADMA) from acutely and chronically administered free L-arginine in humans. Amino Acids, 2015, 47(9), 1893-1908.
[44]
Gunes, D.N.; Kayacelebi, A.A.; Hanff, E.; Lundgren, J.; Redfors, B.; Tsikas, D. Metabolism and distribution of pharmacological homoarginine in plasma and main organs of the anesthetized rat. Amino Acids, 2017, 49(12), 2033-2044.
[45]
Atzler, D.; Gore, M.O.; Ayers, C.R.; Choe, C.U.; Boger, R.H.; de Lemos, J.A.; McGuire, D.K.; Schwedhelm, E. Homoarginine and cardiovascular outcome in the population-based Dallas heart study. Arter. Thromb. Vasc. Biol, 2014, 37(9), 2501-2507.
[46]
Hou, Y.; Hu, S.; Jia, S.; Nawaratna, G.; Che, D.; Wang, F.; Bazer, F.W.; Wu, G. Whole-body synthesis of l-homoarginine in pigs and rats supplemented with L-arginine. Amino Acids, 2016, 48(4), 993-1001.
[47]
Marescau, B.; Deshmukh, D.R.; Kockx, M.; Possemiers, I.; Qureshi, I.A.; Wiechert, P.; De Deyn, P.P. Guanidino compounds in serum, urine, liver, kidney, and brain of man and some ureotelic animals. Metabolism, 1992, 41(5), 526-532.
[48]
Sobczak, A.; Prokopowicz, A.; Szula, M.; Zaciera, M.; Kurek, J.; Radek, M.; Goniewicz, M.L. Do homoarginine and asymmetric dimethylarginine act antagonistically in the cardiovascular system? Circulation, 2014, 78(8), 2096.
[49]
Schlune, A.; Vom Dahl, S.; Haussinger, D.; Ensenauer, R.; Mayatepek, E. Hyperargininemia due to arginase I deficiency: The original patients and their natural history, and a review of the literature. Amino Acids, 2015, 47(9), 1751-1762.
[50]
Meinitzer, A.; Drechsler, C.; Tomaschitz, A.; Pilz, S.; Krane, V.; Wanner, C.; März, W. Homoarginine: A new cardiovascular risk marker in hemodialysis patients. Lab. Med., 2011, 35(3), 153-159.
[51]
Marz, W.; Meinitzer, A.; Drechsler, C.; Pilz, S.; Krane, V.; Kleber, M.E.; Fischer, J.; Winkelmann, B.R.; Bohm, B.O.; Ritz, E.; Wanner, C. Homoarginine, cardiovascular risk, and mortality. Circulation, 2010, 122(10), 967-975.
[52]
Pilz, S.; Meinitzer, A.; Tomaschitz, A.; Drechsler, C.; Ritz, E.; Krane, V.; Wanner, C.; Boehm, B.O.; Marz, W. Low homoarginine concentration is a novel risk factor for heart disease. Heart, 2011, 97(15), 1222-1227.
[53]
Pilz, S.; Tomaschitz, A.; Meinitzer, A.; Drechsler, C.; Ritz, E.; Krane, V.; Wanner, C.; Bohm, B.O.; Marz, W. Low serum homoarginine is a novel risk factor for fatal strokes in patients undergoing coronary angiography. Stroke, 2011, 42(4), 1132-1134.
[54]
Closs, E.; Boissel, J.P.; Habermeier, A.; Rotmann, A. Structure and function of cationic amino acid transporters (CATs). J. Membr. Biol., 2006, 213(2), 67-77.
[55]
Kakoki, M.; Wang, W.; Mattson, D.L. Cationic amino acid transport in the renal medulla and blood pressure regulation. Hypertension, 2002, 39(2), 287-292.
[56]
Haghikia, A.; Kayacelebi, A.A.; Beckmann, B.; Hanff, E.; Gold, R.; Haghikia, A.; Tsikas, D. Serum and cerebrospinal fluid concentrations of homoarginine, arginine, asymmetric and symmetric dimethylarginine, nitrite and nitrate in patients with multiple sclerosis and neuromyelitis optica. Amino Acids, 2015, 47(9), 1837-1845.
[57]
Horster, I.; Weigt-Usinger, K.; Carmann, C.; Chobanyan-Jurgens, K.; Kohler, C.; Schara, U.; Kayacelebi, A.A.; Beckmann, B.; Tsikas, D.; Lucke, T. The l-arginine/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids. Amino Acids, 2015, 47(9), 1853-1863.
[58]
Parolini, C.; Ganzetti, G.S.; Dellera, F.; Froio, A.; Manzini, S.; Busnelli, M.; Meinitzer, A.; Chiesa, G. Effect of homoarginine administration on neointimal thickening in balloon-injured rat carotid arteries. Atherosclerosis, 2015, 241(1), 193-194.
[59]
Davids, M.; Swieringa, E.; Palm, F.; Smith, D.E.C.; Smulders, Y.M.; Scheffer, P.G.; Blom, H.J.; Teerlink, T. Simultaneous determination of asymmetric and symmetric dimethylarginine, l-monomethylarginine, l-arginine, and l-homoarginine in biological samples using stable isotope dilution liquid chromatography tandem mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2012, 9(1), 38-47.
[60]
Kayacelebi, A.A.; Pham, V.V.; Willers, J.; Hahn, A.; Stichtenoth, D.O.; Jordan, J.; Tsikas, D. Plasma homoarginine (hArg) and asymmetric dimethylarginine (ADMA) in patients with rheumatoid arthritis: is homoarginine a cardiovascular corrective in rheumatoid arthritis, an anti-ADMA. Int. J. Cardiol., 2014, 176, 1129-1131.
[61]
Atzler, D.; Appelbaum, S.; Cordts, K.; Ojeda, F.M.; Wild, P.S.; Munzel, T.; Blankenberg, S.; Boger, R.H.; Blettner, M.; Beutel, M.E.; Pfeiffer, N.; Zeller, T.; Lackner, K.J.; Schwedhelm, E. Reference intervals of plasma homoarginine from the German Gutenberg health study. Clin. Chem. Lab. Med., 2016, 54(7), 1231-1237.
[62]
Kozlenkov, A.; Le Du, M.H.; Cuniasse, P.; Ny, T.; Hoylaerts, M.F.; Millan, J.L. Residues determining the binding specificity of uncompetitive inhibitors to tissue-nonspecific alkaline phosphatase. J. Bone Miner. Res., 2004, 19(11), 1862-1872.
[63]
Atzler, D.; Schwedhelm, E.; Choe, C.U. L-homoarginine and cardiovascular disease. Curr. Opin. Clin. Nutr. Metab. Care, 2015, 18(1), 83-88.
[64]
Khalil, A.A.; Tsikas, D.; Akolekar, R.; Jordan, J.; Nicolaides, K.H. Asymmetric dimethylarginine, arginine and homoarginine at 11–13 weeks’ gestation and preeclampsia: A case–control study. J. Hum. Hypertens., 2013, 27(1), 38-43.
[65]
Michel, T. R is for arginine: Metabolism of arginine takes off again, in new directions. Circulation, 2013, 136(11), 1400-1404.
[66]
Alesutan, I.; Feger, M.; Tuffaha, R.; Castor, T.; Musculus, K.; Buehling, S.S.; Heine, C.L.; Kuro, O.M.; Pieske, B.; Schmidt, K.; Tomaschitz, A.; Maerz, W.; Pilz, S.; Meinitzer, A.; Voelkl, J.; Lang, F. Augmentation of phosphate-induced osteo-/chondrogenic transformation of vascular smooth muscle cells by homoarginine. Cardiovasc. Res., 2016, 110(3), 408-418.
[67]
Gambaryan, S.; Tsikas, D. A review and discussion of platelet nitric oxide and nitric oxide synthase: Do blood platelets produce nitric oxide from L-arginine or nitrite. Amino Acids, 2015, 47(9), 1779-1793.
[68]
Moali, C.; Boucher, J.L.; Sari, M.A.; Stuehr, D.J.; Mansuy, D. Substrate specificity of NO synthases: detailed comparison of l-arginine, homo-l-arginine, their N omegahydroxy derivatives, and N omega-hydroxynor-L-arginine. J. Biochem., 1998, 37(29), 10453-10460.
[69]
Pentyala, J.R.S. Sustained nitric oxide generation with l-homoarginine. Res. Commun. Biochem. Cell Mol. Biol., 1999, 3(3/4), 223-232.
[70]
Magnusson, P.; Farley, J.R. Differences in sialic acid residues among bone alkaline phosphatase isoforms: A physical, biochemical, and immunological characterization. Calcif. Tissue Int., 2002, 71(6), 508-518.
[71]
Pilz, S.; Meinitzer, A.; Tomaschitz, A.; Kienreich, K.; Dobnig, H.; Schwarz, M.; Wagner, D.; Drechsler, C.; Piswanger-Solkner, C.; Marz, W.; Fahrleitner-Pammer, A. Associations of homoarginine with bone metabolism and density, muscle strength and mortality: Cross-sectional and prospective data from 506 female nursing home patients. Osteoporos. Int., 2013, 24(1), 377-381.
[72]
Halling, L.C. Biochemical and functional properties of mammalian bone alkaline phosphatase isoforms during osteogenesis; Linköping University Electronic Press, 2016, p. 66.
[73]
Saura, M.; Tarin, C.; Zaragoza, C. Recent insights into the implication of nitric oxide in osteoblast differentiation and proliferation during bone development. Sci. World J., 2010, 10, 624-632.
[74]
Drechsler, C.; Meinitzer, A.; Pilz, S.; Krane, V.; Tomaschitz, A.; Ritz, E.; März, W.; Wanner, C. Homoarginine, heart failure, and sudden cardiac death in haemodialysis patients. Eur. J. Heart Fail., 2011, 13(8), 852-859.
[75]
Köttgen, A.; Glazer, N.L.; Dehghan, A.; Hwang, S.J.; Katz, R.; Li, M.; Yang, Q.; Gudnason, V.; Launer, L.J.; Harris, T.B. Multiple loci associated with indices of renal function and chronic kidney disease. Nat. Genet., 2009, 41(6), 712-717.
[76]
Da Silva, R.P.; Nissim, I.; Brosnan, M.E.; Brosnan, J.T. Creatine synthesis: Hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. Am. J. Physiol. Endocrinol. Metab., 2009, 296(2), 256-261.
[77]
Stöckler-Ipsiroglu, S.; Stromberger, C.; Mühl, A.; Alessandrì, M.G.; Bianchi, M.C.; Tosetti, M.; Cioni, G. Arginine: Glycine amidinotransferase deficiency: The third inborn error of creatine metabolism in humans. Am. J. Hum. Genet., 2001, 65(5), 1127-1133.
[78]
Katz, L.A.; Swain, J.A.; Portman, M.A.; Balaban, R.S. Relation between phosphate metabolites and oxygen consumption of heart in vivo. Am. J. Physiol. Heart Circ. Physiol., 1989, 256(1), 265-274.
[79]
Wallimann, T.; Tokarska-Schlattner, M.; Schlattner, U. The creatine kinase system and pleiotropic effects of creatine. Amino Acids, 2011, 40(5), 1271-1296.
[80]
Collin, P.; Nefussi, J.R.; Wetterwald, A.; Nicolas, V.; Boy-Lefevre, M.L.; Fleisch, H.; Forest, N. Expression of collagen, osteocalcin, and bone alkaline phosphatase in a mineralizing rat osteoblastic cell culture. Calcif. Tissue Int., 1992, 50(2), 175-183.
[81]
Suzuki, K.; Yoshimura, Y.; Hisada, Y.; Matsumoto, A. Sensitivity of intestinal alkaline phosphatase to L-homoarginine and its regulation by subunit-subunit interaction. Jpn. J. Pharmacol., 1994, 64(2), 97-102.
[82]
Tomaschitz, A.; Meinitzer, A.; Pilz, S.; Rus-Machan, J.; Genser, B.; Drechsler, C.; Grammer, T.; Krane, V.; Ritz, E.; Kleber, M.E.; Pieske, B.; Kraigher-Krainer, E.; Fahrleitner-Pammer, A.; Wanner, C.; Boehm, B.O.; Marz, W. Homoarginine, kidney function and cardiovascular mortality risk. Nephrol. Dial. Transplant., 2014, 29(3), 663-671.
[83]
Moncada, S.; Higgs, E.A. The discovery of nitric oxide and its role in vascular biology. Br. J. Pharmacol., 2006, 147(1), 193-201.
[84]
März, W.; Meinitzer, A.; Pilz, S.; Drechsler, C.; Krane, V.; Kleber, M.; Fischer, J.; Winkelmann, B.; Böhm, B.; Ritz, E.; Wanner, C. Ms535 homoarginine independently predicts total and cardiovascular mortality in individuals with angiographic coronary artery disease. Atheroscler. Suppl., 2010, 11(2), 217.
[85]
Pilz, S.; Meinitzer, A.; Tomaschitz, A.; Kienreich, K.; Dobnig, H.; Schwarz, M.; Wagner, D.; Drechsler, C.; Piswanger-Solkner, C.; Marz, W.; Fahrleitner-Pammer, A. Associations of methylarginines and homoarginine with diastolic dysfunction and cardiovascular risk factors in patients with preserved left ventricular ejection fraction. J. Card. Fail., 2014, 20(12), 923-930.
[86]
Deignan, J.L.; Marescau, B.; Livesay, J.C.; Iyer, R.K.; De Deyn, P.P.; Cederbaum, S.D.; Grody, W.W. Increased plasma and tissue guanidino compounds in a mouse model of hyperargininemia. Mol. Genet. Metab., 2008, 93, 172-178.
[87]
Lee, E.K.; Hu, C.; Bhargava, R.; Ponnusamy, R.; Park, H.; Novicoff, S.; Rozengurt, N.; Marescau, B.; De Deyn, P.P.; Stout, D. AAV-based gene therapy prevents neuropathology and results in normal cognitive development in the hyperargininemic mouse. Gene Ther., 2013, 20(8), 785-796.
[88]
Athanasiadou, S.; Russell, K.M.; Kaiser, P.; Kanellos, T.; Burgess, S.T.; Mitchell, M.; Clutton, E.; Naylor, S.W.; Low, C.J.; Hutchings, M.R.; Sparks, N. Genome wide transcriptomic analysis identifies pathways affected by the infusion of Clostridium perfringens culture supernatant in the duodenum of broilers in situ. J. Anim. Sci., 2015, 93(6), 3152-3163.
[89]
Deignan, J.L.; De Deyn, P.P.; Cederbaum, S.D.; Fuchshuber, A.; Roth, B.; Gsell, W.; Marescau, B. Guanidino compound levels in blood, cerebrospinal fluid, and post-mortem brain material of petients with argininemia. Mol. Genet. Metab., 2010, 100, 531-536.
[90]
Hiramatsu, M. A role for guanidino compounds in the brain.Guanidino Compounds in Biology and Medicine; Clark, J.F., Ed.; Springer US: Boston, MA, 2003, pp. 57-62.
[91]
Shiraga, H.; Watanabe, Y.; Mori, A. Guanidino compound levels in the serum of healthy adults and epileptic patients. Epilepsy Res., 1991, 8(2), 142-148.
[92]
Vodopiutz, J.; Item, C.B.; Häusler, M.; Korall, H.; Bodamer, O.A. Severe speech delay as the presenting symptom of guanidinoacetate methyltransferase deficiency. J. Child Neurol., 2007, 22(6), 773-774.
[93]
Gordon, N. Guanidinoacetate methyltransferase deficiency (GAMT). Brain Dev., 2010, 32(2), 79-81.
[94]
Yokoi, I.; Toma, J.; Mori, A. The effect of homoarginine on the EEG of rats. Neurochem. Pathol., 1984-1985, 2, 295-300.
[95]
Lambert, L.E.; French, J.F.; Whitten, J.P.; Baron, B.M.; McDonald, I.A. Characterization of cell selectivity of two novel inhibitors of nitric oxide synthesis. Eur. J. Pharmacol., 1992, 216(1), 131-134.
[96]
Sase, A.; Nawaratna, G.; Hu, S.; Wu, G.; Lubec, G. Decreased hippocampal homoarginine and increased nitric oxide and nitric oxide synthase levels in rats’ parallel training in a radial arm maze. Amino Acids, 2016, 48(9), 2197-2204.
[97]
Aldridge, C.R.; Collard, K.J. The characteristics of arginine transport by rat cerebellar and cortical synaptosomes. Neurochem. Res., 1996, 21(12), 1539-1546.
[98]
De Deyn, P.P.; Marescau, B.; MacDonald, R.L. Epilepsy and the GABA-hypothesis a brief review and some examples. Acta Neurol. Belg., 1990, 90(2), 65-81.
[99]
Delwing-de Lima, D.; Wollinger, L.F.; Casagrande, A.C.M.; Delwing, F.; da Cruz, J.G.P.; Wyse, A.T.S.; Delwing-Dal Magro, D. Guanidino compounds inhibit acetylcholinesterase and butyrylcholinesterase activities: effect neuroprotector of vitamins E plus C. Int. J. Dev. Neurosci., 2010, 28(6), 465-473.
[100]
Sato, T.K.; Sakurada, S.; Sakurada, T.; Kisara, K.; Sasaki, Y.; Akutsu, Y.; Suzuki, K. Comparison of the antinociceptive effect between the cyclic dipeptide cyclo [Tyr (Et)-homoarginine] and the linear dipeptide Boc-Tyr (Et)-homoarginine-OMe in rats. Jpn. J. Pharmacol., 1984, 34(1), 1-8.
[101]
White, M.F.; Christensen, H.N. The two-way flux of cationic amino acids across the plasma membrane of mammalian cells is largely explained by a single transport system. J. Biol. Chem., 1982, 257(17), 10069-10080.
[102]
Porcelli, V.; Fiermonte, G.; Longo, A.; Palmieri, F. The human gene SLC25A29, of solute carrier family 25, encodes a mitochondrial transporter of basic amino acids. J. Biol. Chem., 2014, 289(19), 13374-13384.
[103]
Kerwin, J.F.J.; Lancaster, J.R.J.; Feldman, P.L. Nitric oxide: A new paradigm for second messengers. J. Med. Chem., 1995, 38(22), 4343-4362.
[104]
Bernstein, H.G.; Hölzl, G.; Dobrowolny, H.; Hildebrandt, J.; Trübner, K.; Krohn, M.; Bogerts, B.; Pahnke, J. Vascular and extravascular distribution of the ATP-binding cassette transporters ABCB1 and ABCC1 in aged human brain and pituitary. Mech. Ageing Dev., 2014, 141, 12-21.
[105]
Stockebrand, M.; Hornig, S.; Neu, A.; Atzler, D.; Cordts, K.; Boger, R.H.; Isbrandt, D.; Schwedhelm, E.; Choe, C.U. Homoarginine supplementation improves blood glucose in diet-induced obese mice. Amino Acids, 2015, 47(9), 1921-1929.
[106]
Jager, G.J.; Severens, J.L.; Thornbury, J.R.; de La Rosette, J.J.; Ruijs, S.H.; Barentsz, J.O. Prostate cancer staging: Should MR imaging be used? A decision analytic approach. Radiology, 2000, 215(2), 445-451.
[107]
Cockell, A.P.; Poston, L. Flow-mediated vasodilatation is enhanced in normal pregnancy but reduced in preeclampsia. Hypertension, 1997, 30(2), 247-251.
[108]
Ndika, J.D.; Johnston, K.; Barkovich, J.A.; Wirt, M.D.; O’Neill, P.; Betsalel, O.T.; Jakobs, C.; Salomons, G.S. Developmental progress and creatine restoration upon long-term creatine supplementation of a patient with arginine: Glycine amidinotransferase deficiency. Mol. Genet. Metab., 2012, 106(1), 48-54.
[109]
Wu, X.; Pittman, H.E.; Prior, R.L. Pelargonidin is absorbed and metabolized differently than cyanidin after marionberry consumption in pigs. J. Nutr., 2004, 134(10), 2603-2610.
[110]
Harding, J.E. The nutritional basis of the fetal origins of adult disease. Int. J. Epidemiol., 2001, 30(1), 15-23.
[111]
Belkacemi, L.; Jelks, A.; Chen, C.H.; Ross, M.G.; Desai, M. Altered placental development in undernourished rats: Role of maternal glucocorticoids. Reprod. Biol. Endocrinol., 2011, 9(1), 105.
[112]
Grazul-Bilska, A.T.; Borowicz, P.P.; Johnson, M.L.; Minten, M.A.; Bilski, J.J.; Wroblewski, R.; Redmer, D.A.; Reynolds, L.P. Placental development during early pregnancy in sheep: vascular growth and expression of angiogenic factors in maternal placenta. Reproduction, 2010, 140(1), 165-174.
[113]
Wu, W.H.; Meijer, O.G.; Uegaki, K.; Mens, J.M.A.; van Dieen, J.H.; Wuisman, P.I.J.M.; Östgaard, H.C. Pregnancy-related pelvic girdle pain (PPP), I: Terminology, clinical presentation, and prevalence. Eur. Spine J., 2004, 13(7), 575-589.
[114]
Alan, W.B.; Richard, A.E. Regulation of placental nutrient transport and implications for fetal growth. Nutr. Res. Rev., 2002, 15, 211-230.
[115]
Coan, P.M.; Vaughan, O.R.; Sekita, Y.; Finn, S.L.; Burton, G.J.; Constancia, M.; Fowden, A.L. Adaptations in placental phenotype support fetal growth during undernutrition of pregnant mice. J. Physiol., 2010, 588(3), 527-538.
[116]
Wu, G.; Bazer, F.W.; Davis, T.A.; Kim, S.W.; Li, P.; Marc Rhoads, J.; Carey Satterfield, M.; Smith, S.B.; Spencer, T.E.; Yin, Y. Arginine metabolism and nutrition in growth, health and disease. Amino Acids, 2009, 37(1), 153-168.
[117]
Lassala, A.; Bazer, F.W.; Cudd, T.A.; Datta, S.; Keisler, D.H.; Satterfield, M.C.; Spencer, T.E.; Wu, G. Parenteral administration of L-arginine prevents fetal growth restriction in undernourished ewes. J. Nutr., 2010, 140(7), 1242-1248.
[118]
Mateo, R.D.; Wu, G.; Bazer, F.W.; Park, J.C.; Shinzato, I.; Kim, S.W. Dietary L-arginine supplementation enhances the reproductive performance of gilts. J. Nutr., 2007, 137(3), 652-652.
[119]
Vosatka, R.J.; Hassoun, P.M.; Harvey-Wilkes, K.B. Dietary l-arginine prevents fetal growth restriction in rats. Am. J. Obstet. Gynecol., 1998, 178(2), 242-246.
[120]
Xiao, X.M.; Li, L.P. L-arginine treatment for asymmetric fetal growth restriction. Int. J. Gynaecol. Obstet., 2005, 88(1), 15-18.
[121]
Zeng, X.; Wang, F.; Fan, X.; Yang, W.; Zhou, B.; Li, P.; Yin, Y.; Wu, G.; Wang, J. Dietary arginine supplementation during early pregnancy enhances embryonic survival in rats. Am. Soc. Nutr, 2008, 138(8), 1421-1425.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 2
Year: 2019
Page: [184 - 193]
Pages: 10
DOI: 10.2174/1389203719666181026170049
Price: $65

Article Metrics

PDF: 21
HTML: 6