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Drug Metabolism Letters

Editor-in-Chief

ISSN (Print): 1872-3128
ISSN (Online): 1874-0758

Review Article

Physiological and Pathophysiological Role of Cysteine Metabolism in Human Metabolic Syndrome

Author(s): Arunachalam Muthuraman*, Muthusamy Ramesh*, Sohrab A. Shaikh, Subramanian Aswinprakash and Dhamodharan Jagadeesh

Volume 14, Issue 3, 2021

Page: [177 - 192] Pages: 16

DOI: 10.2174/1872312814666211210111820

Price: $65

Abstract

Abstract: Cysteine is one of the major intermediate products of cellular amino-acid metabolism. It is a semi-essential amino acid for protein synthesis. Besides, it is also employed in the regulation of major endogenous anti-oxidant molecule i.e., reduced glutathione (GSH). Further, it is a precursor of multiple sulfur-containing molecules like hydrogen sulfide, lanthionine, taurine, coenzyme A and biotin. It is also one of the key molecules for post-translational modifications of various cellular proteins. In physiological conditions, it is employed in the sulfhydration process and plays a key role in the physiology modification of the inflammatory process in various organs, including the neurological system. The catabolism of cysteine is regulated by cysteine dioxygenase enzyme activity. The dysregulated conditions of cysteine and cysteine-associated hydrogen sulfide metabolism are widely employed in the acceleration of the neurodegenerative process. Moreover, the upregulation of cysteine and hydrogen sulfide synthesis occurs via the reverse trans-sulfuration process. This process helps to manage the worsening of a pathological condition of a cellular system. Moreover, it is also employed in the accumulation of homocysteine contents. Further, both cysteine and homocysteine molecules are widely accepted as biomarkers for various types of diseases. Therefore, the targets involved in the regulation of cysteine have been considered as valid targets to treat various disorders like cardiac disease, ischemic stroke, diabetes, cancer, and renal dysfunction.

Keywords: Biomarker, homocysteine, hydrogen sulfide, reduced glutathione, stroke, metabolic syndrome.

Graphical Abstract
[1]
Badelin, V.G.; Mezhevoi, I.N.; Tyunina, E.Y. Measuring the enthalpies of interaction between glycine, L-cysteine, glycylglycine, and sodium dodecyl sulfate in aqueous solutions. Russ. J. Phys. Chem. A., 2017, 91(3), 521-524.
[http://dx.doi.org/10.1134/S0036024417030025]
[2]
Paul, B.D. Neuroprotective roles of the reverse transsulfuration pathway in Alzheimer’s disease. Front. Aging Neurosci., 2021, 13, 659402.
[http://dx.doi.org/10.3389/fnagi.2021.659402] [PMID: 33796019]
[3]
Xue, C.; Peng, Y.; Chen, A.; Peng, L.; Luo, S. Drastically inhibited nZVI-Fenton oxidation of organic pollutants by cysteine: Multiple roles in the nZVI/O2/hv system. J. Colloid Interface Sci., 2021, 582(Pt A), 22-29.
[http://dx.doi.org/10.1016/j.jcis.2020.08.036] [PMID: 32810690]
[4]
Pople, J.M.M.; Chalker, J.M. A critical evaluation of probes for cysteine sulfenic acid. Curr. Opin. Chem. Biol., 2021, 60, 55-65.
[http://dx.doi.org/10.1016/j.cbpa.2020.07.011] [PMID: 32866852]
[5]
Abbassi, M.S.; Othman, A.A.; Briki, K.; Lahrech, M.B. Synthesis of diazole-thiols derivatives from L-cysteine: Characterization, complex formation with Ni (II), Cu (II) and evaluation of their antibacterial activity. J. Saudi Chem. Soc., 2021, 25(5), 101230.
[http://dx.doi.org/10.1016/j.jscs.2021.101230]
[6]
Shrivastava, M.; Feng, J.; Coles, M.; Clark, B.; Islam, A.; Dumeaux, V.; Whiteway, M. Modulation of the complex regulatory network for methionine biosynthesis in fungi. Genetics, 2021, 217(2), iyaa049.
[http://dx.doi.org/10.1093/genetics/iyaa049]
[7]
Teodósio, R.; Engrola, S.; Cabano, M.; Colen, R.; Masagounder, K.; Aragão, C. Metabolic and nutritional responses of Nile tilapia juveniles to dietary methionine sources. Br. J. Nutr., 2021, 2021, 1-12.
[http://dx.doi.org/10.1017/S0007114521001008] [PMID: 33749566]
[8]
Chevallier, V.; Zoller, M.; Kochanowski, N.; Andersen, M.R.; Workman, C.T.; Malphettes, L. Use of novel cystine analogs to decrease oxidative stress and control product quality. J. Biotechnol., 2021, 327, 1-8.
[http://dx.doi.org/10.1016/j.jbiotec.2020.12.011] [PMID: 33373629]
[9]
Sreekumar, P.G.; Ferrington, D.A.; Kannan, R. Glutathione metabolism and the novel role of mitochondrial GSH in retinal degeneration. Antioxidants, 2021, 10(5), 661.
[http://dx.doi.org/10.3390/antiox10050661] [PMID: 33923192]
[10]
Yoneda, J.; Nishikawa, S.; Kurihara, S. Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. Res. Square, 2021, [Epub ahead of print].
[http://dx.doi.org/10.21203/rs.3.rs-228405/v1]
[11]
Paul, B.D.; Sbodio, J.I.; Snyder, S.H. Cysteine metabolism in neuronal redox homeostasis. Trends Pharmacol. Sci., 2018, 39(5), 513-524.
[http://dx.doi.org/10.1016/j.tips.2018.02.007] [PMID: 29530337]
[12]
Chung, H.S.; Wang, S.B.; Venkatraman, V.; Murray, C.I.; Van Eyk, J.E. Cysteine oxidative posttranslational modifications: Emerging regulation in the cardiovascular system. Circ. Res., 2013, 112(2), 382-392.
[http://dx.doi.org/10.1161/CIRCRESAHA.112.268680] [PMID: 23329793]
[13]
Joseph, J.; Giczewska, A.; Alhanti, B.; Cheema, A.K.; Handy, D.E.; Mann, D.L.; Loscalzo, J.; Givertz, M.M. Associations of methyl donor and methylation inhibitor levels during anti-oxidant therapy in heart failure. J. Physiol. Biochem., 2021, 77(2), 295-304.
[http://dx.doi.org/10.1007/s13105-021-00797-x] [PMID: 33595776]
[14]
Backos, D.S.; Fritz, K.S.; Roede, J.R.; Petersen, D.R.; Franklin, C.C. Posttranslational modification and regulation of glutamate- cysteine ligase by the α,β-unsaturated aldehyde 4-hydroxy-2-nonenal. Free Radic. Biol. Med., 2011, 50(1), 14-26.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.10.694] [PMID: 20970495]
[15]
Paszewski, A.; Grabski, J. Enzymatic lesions in methionine mutants of Aspergillus nidulans: Role and regulation of an alternative pathway for cysteine and methionine synthesis. J. Bacteriol., 1975, 124(2), 893-904.
[http://dx.doi.org/10.1128/jb.124.2.893-904.1975] [PMID: 1102536]
[16]
Kluijtmans, L.A.; Boers, G.H.; Stevens, E.M.; Renier, W.O.; Kraus, J.P.; Trijbels, F.J.; van den Heuvel, L.P.; Blom, H.J. Defective cystathionine beta-synthase regulation by S-adenosylmethionine in a partially pyridoxine responsive homocystinuria patient. J. Clin. Invest., 1996, 98(2), 285-289.
[http://dx.doi.org/10.1172/JCI118791] [PMID: 8755636]
[17]
Nin, D.S.; Idres, S.B.; Deng, L.W. Cysteine metabolism in cancer progression and therapy resistance. Oxidative Stress: Human Diseases and Medicine, 2021, 155.
[18]
Xiao, Q.; Xiong, L.; Tang, J.; Li, L.; Li, L. Hydrogen sulfide in skin diseases: A novel mediator and therapeutic target. Oxid. Med. Cell. Longev., 2021, 2021, 6652086.
[http://dx.doi.org/10.1155/2021/6652086] [PMID: 33986916]
[19]
Göbbels, L.; Poehlein, A.; Dumnitch, A.; Egelkamp, R.; Kröger, C.; Haerdter, J.; Hackl, T.; Feld, A.; Weller, H.; Daniel, R.; Streit, W.R.; Schoelmerich, M.C. Cysteine: An overlooked energy and carbon source. Sci. Rep., 2021, 11(1), 2139.
[http://dx.doi.org/10.1038/s41598-021-81103-z] [PMID: 33495538]
[20]
Chua, B.H.; Giger, K.E.; Kleinhans, B.J.; Robishaw, J.D.; Morgan, H.E. Differential effects of cysteine on protein and coenzyme A synthesis in rat heart. Am. J. Physiol., 1984, 247(1 Pt 1), C99-C106.
[http://dx.doi.org/10.1152/ajpcell.1984.247.1.C99] [PMID: 6204541]
[21]
Mellis, A.T.; Misko, A.L.; Arjune, S.; Liang, Y.; Erdélyi, K.; Ditrói, T.; Kaczmarek, A.T.; Nagy, P.; Schwarz, G. The role of glutamate oxaloacetate transaminases in sulfite biosynthesis and H2S metabolism. Redox Biol., 2021, 38, 101800.
[http://dx.doi.org/10.1016/j.redox.2020.101800] [PMID: 33271457]
[22]
Wu, B.; Liu, F.; Fang, W.; Yang, T.; Chen, G.H.; He, Z.; Wang, S. Microbial sulfur metabolism and environmental implications. Sci. Total Environ., 2021, 778, 146085.
[http://dx.doi.org/10.1016/j.scitotenv.2021.146085] [PMID: 33714092]
[23]
Poltorack, C.D.; Dixon, S.J. Understanding the role of cysteine in ferroptosis: Progress & paradoxes. FEBS J., 2021, [Epub ahead of print].
[http://dx.doi.org/10.1111/febs.15842] [PMID: 33773039]
[24]
Zhu, Y.; Liu, L.; Tan, D.; Sun, W.; Ke, Q.; Yue, X.; Bai, B. S-desulfurization: A different covalent modification mechanism from persulfidation by GSH. Free Radic. Biol. Med., 2021, 167, 54-65.
[http://dx.doi.org/10.1016/j.freeradbiomed.2021.02.031] [PMID: 33711417]
[25]
Arif, Y.; Hayat, S.; Yusuf, M.; Bajguz, A. Hydrogen sulfide: A versatile gaseous molecule in plants. Plant Physiol. Biochem., 2021, 158, 372-384.
[http://dx.doi.org/10.1016/j.plaphy.2020.11.045] [PMID: 33272793]
[26]
Stipanuk, M.H.; Dominy, J.E.J., Jr; Lee, J.I.; Coloso, R.M. Mammalian cysteine metabolism: New insights into regulation of cysteine metabolism. J. Nutr., 2006, 136(6), 1652S-1659S.
[http://dx.doi.org/10.1093/jn/136.6.1652S] [PMID: 16702335]
[27]
Stipanuk, M.H.; Ueki, I. Dealing with methionine/homocysteine sulfur: Cysteine metabolism to taurine and inorganic sulfur. J. Inherit. Metab. Dis., 2011, 34(1), 17-32.
[http://dx.doi.org/10.1007/s10545-009-9006-9] [PMID: 20162368]
[28]
Stipanuk, M.H.; Ueki, I.; Dominy, J.E., Jr; Simmons, C.R.; Hirschberger, L.L. Cysteine dioxygenase: A robust system for regulation of cellular cysteine levels. Amino Acids, 2009, 37(1), 55-63.
[http://dx.doi.org/10.1007/s00726-008-0202-y] [PMID: 19011731]
[29]
Lee, J.I.; Kang, J.; Stipanuk, M.H. Differential regulation of glutamate-cysteine ligase subunit expression and increased holoenzyme formation in response to cysteine deprivation. Biochem. J., 2006, 393(Pt 1), 181-190.
[http://dx.doi.org/10.1042/BJ20051111] [PMID: 16137247]
[30]
Toroser, D.; Yarian, C.S.; Orr, W.C.; Sohal, R.S. Mechanisms of gamma-glutamylcysteine ligase regulation. Biochim. Biophys. Acta, 2006, 1760(2), 233-244.
[http://dx.doi.org/10.1016/j.bbagen.2005.10.010] [PMID: 16324789]
[31]
Jain, S.K.; Huning, L.; Micinski, D. Hydrogen sulfide upregulates glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit, and glutathione and inhibits interleukin-1β secretion in monocytes exposed to high glucose levels. Metab. Syndr. Relat. Disord., 2014, 12(5), 299-302.
[http://dx.doi.org/10.1089/met.2014.0022] [PMID: 24665821]
[32]
Dominy, J.E., Jr; Hwang, J.; Guo, S.; Hirschberger, L.L.; Zhang, S.; Stipanuk, M.H. Synthesis of amino acid cofactor in cysteine dioxygenase is regulated by substrate and represents a novel post- translational regulation of activity. J. Biol. Chem., 2008, 283(18), 12188-12201.
[http://dx.doi.org/10.1074/jbc.M800044200] [PMID: 18308719]
[33]
Park, T.; Rogers, Q.R.; Morris, J.G. High dietary protein and taurine increase cysteine desulfhydration in kittens. J. Nutr., 1999, 129(12), 2225-2230.
[http://dx.doi.org/10.1093/jn/129.12.2225] [PMID: 10573554]
[34]
Arjune, S.; Schwarz, G.; Belaidi, A.A. Involvement of the Cys- Tyr cofactor on iron binding in the active site of human cysteine dioxygenase. Amino Acids, 2015, 47(1), 55-63.
[http://dx.doi.org/10.1007/s00726-014-1843-7] [PMID: 25261132]
[35]
Lim, J.C.; Choi, H.I.; Park, Y.S.; Nam, H.W.; Woo, H.A.; Kwon, K.S.; Kim, Y.S.; Rhee, S.G.; Kim, K.; Chae, H.Z. Irreversible oxidation of the active-site cysteine of peroxiredoxin to cysteine sulfonic acid for enhanced molecular chaperone activity. J. Biol. Chem., 2008, 283(43), 28873-28880.
[http://dx.doi.org/10.1074/jbc.M804087200] [PMID: 18725414]
[36]
Malatesta, M.; Mori, G.; Acquotti, D.; Campanini, B.; Peracchi, A.; Antin, P.B.; Percudani, R. Birth of a pathway for sulfur metabolism in early amniote evolution. Nat. Ecol. Evol., 2020, 4(9), 1239-1246.
[http://dx.doi.org/10.1038/s41559-020-1232-4] [PMID: 32601391]
[37]
Hensley, K.; Denton, T.T. Alternative functions of the brain transsulfuration pathway represent an underappreciated aspect of brain redox biochemistry with significant potential for therapeutic engagement. Free Radic. Biol. Med., 2015, 78, 123-134.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.10.581] [PMID: 25463282]
[38]
Loginova, I.V.; Rubtsova, S.A.; Kuchin, A.V. Oxidation by chlorine dioxide of methionine and cysteine derivatives to sulfoxides. Chem. Nat. Compd., 2008, 44(6), 752-754.
[http://dx.doi.org/10.1007/s10600-009-9182-8]
[39]
Li, F.; Li, Y.; Yang, X.; Han, X.; Jiao, Y.; Wei, T.; Yang, D.; Xu, H.; Nie, G. Highly fluorescent chiral N-S-doped carbon dots from cysteine: Affecting cellular energy metabolism. Angew. Chem. Int. Ed. Engl., 2018, 57(9), 2377-2382.
[http://dx.doi.org/10.1002/anie.201712453] [PMID: 29359840]
[40]
Tian, H.; Zhou, Y.; Tang, L.; Wu, F.; Deng, Z.; Lin, B.; Huang, P.; Wei, S.; Zhao, D.; Zheng, J.; Zhong, N.; Ran, P. High-dose N-acetylcysteine for long-term, regular treatment of early-stage chronic obstructive pulmonary disease (GOLD I-II): Study protocol for a multicenter, double-blinded, parallel-group, randomized controlled trial in China. Trials, 2020, 21(1), 780.
[http://dx.doi.org/10.1186/s13063-020-04701-8] [PMID: 32917271]
[41]
Ezeriņa, D.; Takano, Y.; Hanaoka, K.; Urano, Y.; Dick, T.P. N-acetyl cysteine functions as a fast-acting antioxidant by triggering intracellular H(2)S and sulfane sulfur production. Cell Chem. Biol., 2018, 25(4), 447-459.e4.
[http://dx.doi.org/10.1016/j.chembiol.2018.01.011] [PMID: 29429900]
[42]
Fox, A.N.; Nation, B.E.; Autry, M.T.; Johnson, P.N. Possible role for acetylcysteine as a treatment for acute liver failure secondary to antitubercular medication use. Am. J. Health Syst. Pharm., 2020, 77(18), 1482-1487.
[http://dx.doi.org/10.1093/ajhp/zxaa202] [PMID: 32885827]
[43]
Romero, L.C.; Aroca, M.Á.; Laureano-Marín, A.M.; Moreno, I.; García, I.; Gotor, C. Cysteine and cysteine-related signaling pathways in Arabidopsis thaliana. Mol. Plant, 2014, 7(2), 264-276.
[http://dx.doi.org/10.1093/mp/sst168] [PMID: 24285094]
[44]
Liew, Y.F.; Shaw, N.S. Mitochondrial cysteine desulfurase iron- sulfur cluster S and aconitase are post-transcriptionally regulated by dietary iron in skeletal muscle of rats. J. Nutr., 2005, 135(9), 2151-2158.
[http://dx.doi.org/10.1093/jn/135.9.2151] [PMID: 16140891]
[45]
Rehman, T.; Shabbir, M.A.; Inam-Ur-Raheem, M.; Manzoor, M.F.; Ahmad, N.; Liu, Z.W.; Ahmad, M.H.; Siddeeg, A.; Abid, M.; Aadil, R.M. Cysteine and homocysteine as biomarker of various diseases. Food Sci. Nutr., 2020, 8(9), 4696-4707.
[http://dx.doi.org/10.1002/fsn3.1818] [PMID: 32994931]
[46]
Bak, D.W.; Bechtel, T.J.; Falco, J.A.; Weerapana, E. Cysteine reactivity across the subcellular universe. Curr. Opin. Chem. Biol., 2019, 48, 96-105.
[http://dx.doi.org/10.1016/j.cbpa.2018.11.002] [PMID: 30508703]
[47]
Spinelli, J.B.; Haigis, M.C. The multifaceted contributions of mitochondria to cellular metabolism. Nat. Cell Biol., 2018, 20(7), 745-754.
[http://dx.doi.org/10.1038/s41556-018-0124-1] [PMID: 29950572]
[48]
Cardenas-Rodriguez, M.; Chatzi, A.; Tokatlidis, K. Iron-sulfur clusters: From metals through mitochondria biogenesis to disease. Eur. J. Biochem., 2018, 23(4), 509-520.
[http://dx.doi.org/10.1007/s00775-018-1548-6] [PMID: 29511832]
[49]
Bragulla, H.H.; Homberger, D.G. Structure and functions of keratin proteins in simple, stratified, keratinized and cornified epithelia. J. Anat., 2009, 214(4), 516-559.
[http://dx.doi.org/10.1111/j.1469-7580.2009.01066.x] [PMID: 19422428]
[50]
Alibardi, L. Presence of a glycine-cysteine-rich beta-protein in the oberhautchen layer of snake epidermis marks the formation of the shedding layer. Protoplasma, 2014, 251(6), 1511-1520.
[http://dx.doi.org/10.1007/s00709-014-0655-7] [PMID: 24817366]
[51]
Elshorbagy, A.K.; Valdivia-Garcia, M.; Mattocks, D.A.L.; Plummer, J.D.; Smith, A.D.; Drevon, C.A.; Refsum, H.; Perrone, C.E. Cysteine supplementation reverses methionine restriction effects on rat adiposity: Significance of stearoyl-coenzyme A desaturase. J. Lipid Res., 2011, 52(1), 104-112.
[http://dx.doi.org/10.1194/jlr.M010215] [PMID: 20871132]
[52]
Sperk, M.; Mikaeloff, F.; Svensson-Akusjärvi, S.; Krishnan, S.; Ponnan, S.M.; Ambikan, A.T.; Nowak, P.; Sönnerborg, A.; Neogi, U. Distinct lipid profile, low-level inflammation, and increased antioxidant defense signature in HIV-1 elite control status. iScience, 2021, 24(2), 102111.
[http://dx.doi.org/10.1016/j.isci.2021.102111] [PMID: 33659876]
[53]
Sampath, W.; Rathnayake, R.; Yang, M.; Zhang, W.; Mai, K. Roles of dietary taurine in fish nutrition. Mar. Life Sci. Technol., 2020, 2, 360-375.
[http://dx.doi.org/10.1007/s42995-020-00051-1]
[54]
Watson, W.H.; Greenwell, J.C.; Zheng, Y.; Furmanek, S.; Torres- Gonzalez, E.; Ritzenthaler, J.D.; Roman, J. Impact of sex, age and diet on the cysteine/cystine and glutathione/glutathione disulfide plasma redox couples in mice. J. Nutr. Biochem., 2020, 84, 108431.
[http://dx.doi.org/10.1016/j.jnutbio.2020.108431] [PMID: 32615368]
[55]
Ali, A.S.; Chen, R.; Raju, R.; Kshirsagar, R.; Gilbert, A.; Zang, L.; Karger, B.L.; Ivanov, A.R. Multi-omics reveals impact of cysteine feed concentration and resulting redox imbalance on cellular energy metabolism and specific productivity in CHO cell bioprocessing. Biotechnol. J., 2020, 15(8), e1900565.
[http://dx.doi.org/10.1002/biot.201900565] [PMID: 32170810]
[56]
Blachier, F.; Andriamihaja, M.; Blais, A. Sulfur-containing amino acids and lipid metabolism. J. Nutr., 2020, 150(Suppl. 1), 2524S-2531S.
[http://dx.doi.org/10.1093/jn/nxaa243] [PMID: 33000164]
[57]
Poerwoatmodjo, A.; Schenk, G.J.; Geurts, J.J.G.; Luchicchi, A. Cysteine proteases and mitochondrial instability: A possible vicious cycle in MS myelin? Front. Cell. Neurosci., 2020, 14, 612383.
[http://dx.doi.org/10.3389/fncel.2020.612383] [PMID: 33335477]
[58]
Kosuge, Y. Neuroprotective mechanisms of S-allyl-L-cysteine in neurological disease. Exp. Ther. Med., 2020, 19(2), 1565-1569.
[PMID: 32010340]
[59]
Parsanathan, R.; Achari, A.E.; Manna, P.; Jain, S.K. L-cysteine and vitamin D co-supplementation alleviates markers of musculoskeletal disorders in vitamin D-deficient high-fat diet-fed mice. Nutrients, 2020, 12(11), 3406.
[http://dx.doi.org/10.3390/nu12113406] [PMID: 33171932]
[60]
Ghanemi, A.; Yoshioka, M.; St-Amand, J. Secreted protein acidic and rich in cysteine as a regeneration factor: Beyond the tissue repair. Life (Basel), 2021, 11(1), 38.
[http://dx.doi.org/10.3390/life11010038] [PMID: 33435573]
[61]
Ferreira, D.M.S.; Cheng, A.J.; Agudelo, L.Z.; Cervenka, I.; Chaillou, T.; Correia, J.C.; Porsmyr-Palmertz, M.; Izadi, M.; Hansson, A.; Martínez-Redondo, V.; Valente-Silva, P.; Pettersson-Klein, A.T.; Estall, J.L.; Robinson, M.M.; Nair, K.S.; Lanner, J.T.; Ruas, J.L. LIM and cysteine-rich domains 1 (LMCD1) regulates skeletal muscle hypertrophy, calcium handling, and force. Skelet. Muscle, 2019, 9(1), 26.
[http://dx.doi.org/10.1186/s13395-019-0214-1] [PMID: 31666122]
[62]
Jain, S. L-cysteine supplementation increases blood levels of hydrogen sulfide and nitrite, and decreases insulin resistance and vascular inflammation in zucker diabetic rats. Curr. Dev. Nutr., 2020, 4, 405.
[http://dx.doi.org/10.1093/cdn/nzaa045_038]
[63]
Li, P.; Yin, Y.L.; Li, D.; Kim, S.W.; Wu, G. Amino acids and immune function. Br. J. Nutr., 2007, 98(2), 237-252.
[http://dx.doi.org/10.1017/S000711450769936X] [PMID: 17403271]
[64]
Kwon, D.H.; Lee, H.; Park, C.; Hong, S.H.; Hong, S.H.; Kim, G.Y.; Cha, H.J.; Kim, S.; Kim, H.S.; Hwang, H.J.; Choi, Y.H. Glutathione induced immune-stimulatory activity by promoting m1- like macrophages polarization via potential ROS scavenging capacity. Antioxidants, 2019, 8(9), 413.
[http://dx.doi.org/10.3390/antiox8090413] [PMID: 31540482]
[65]
Pérez de la Lastra, J.M.; Andrés-Juan, C.; Plou, F.J.; Pérez-Lebeña, E. Impact of zinc, glutathione, and polyphenols as antioxidants in the immune response against SARS-CoV-2. Processes (Basel), 2021, 9(3), 506.
[http://dx.doi.org/10.3390/pr9030506]
[66]
Kennedy, L.; Sandhu, J.K.; Harper, M.E.; Cuperlovic-Culf, M. Role of glutathione in cancer: From mechanisms to therapies. Biomolecules, 2020, 10(10), 1429.
[http://dx.doi.org/10.3390/biom10101429] [PMID: 33050144]
[67]
Eroglu, N.; Erduran, E.; Reis, G.P.; Bahadır, A. Therapeutic effect of N-acetylcysteine on chemotherapy-induced liver injury. Ir. J. Med. Sci., 2020, 189(4), 1189-1194.
[http://dx.doi.org/10.1007/s11845-020-02219-1] [PMID: 32239424]
[68]
Clemente Plaza, N.; Reig García-Galbis, M.; Martínez-Espinosa, R.M. Effects of the usage of L-cysteine (L-cys) on human health. Molecules, 2018, 23(3), 575.
[http://dx.doi.org/10.3390/molecules23030575] [PMID: 29510494]
[69]
Li, T.; Wang, L.; Hu, Q.; Liu, S.; Bai, X.; Xie, Y.; Zhang, T.; Bo, S.; Gao, X.; Wu, S.; Li, G.; Wang, Z. Neuroprotective roles of L- cysteine in attenuating early brain injury and improving synaptic density via the cbs/h(2)s pathway following subarachnoid hemorrhage in rats. Front. Neurol., 2017, 8, 176.
[http://dx.doi.org/10.3389/fneur.2017.00176] [PMID: 28512446]
[70]
Kostić, S.; Mićovic, Ž.; Andrejević, L.; Cvetković, S.; Stamenković, A.; Stanković, S.; Obrenović, R.; Labudović-Borović, M.; Hrnčić, D.; Jakovljević, V.; Djurić, D. The effects of L-cysteine and N-acetyl-L-cysteine on homocysteine metabolism and haemostatic markers, and on cardiac and aortic histology in subchronically methionine-treated Wistar male rats. Mol. Cell. Biochem., 2019, 451(1-2), 43-54.
[http://dx.doi.org/10.1007/s11010-018-3391-z] [PMID: 29936684]
[71]
Ghafarizadeh, A.; Malmir, M.; Naderi Noreini, S.; Faraji, T. Antioxidant effects of N-acetylcysteine on the male reproductive system: A systematic review. Andrologia, 2021, 53(1), e13898.
[http://dx.doi.org/10.1111/and.13898] [PMID: 33167060]
[72]
Tariq, S.; Tariq, S.; Khaliq, S.; Lone, K.P. Serum resistin levels as predictor of low bone mineral density in postmenopausal women. Health Care Women Int., 2020, 1-10.
[PMID: 32744891]
[73]
Blachier, F.; Beaumont, M.; Kim, E. Cysteine-derived hydrogen sulfide and gut health: A matter of endogenous or bacterial origin. Curr. Opin. Clin. Nutr. Metab. Care, 2019, 22(1), 68-75.
[http://dx.doi.org/10.1097/MCO.0000000000000526] [PMID: 30461448]
[74]
Tardiolo, G.; Bramanti, P.; Mazzon, E. Overview on the effects of N-acetylcysteine in neurodegenerative diseases. Molecules, 2018, 23(12), 3305.
[http://dx.doi.org/10.3390/molecules23123305] [PMID: 30551603]
[75]
Ågren, L.; Elfsmark, L.; Akfur, C.; Hägglund, L.; Ekstrand-Hammarström, B.; Jonasson, S. N-acetyl cysteine protects against chlorine-induced tissue damage in an ex vivo model. Toxicol. Lett., 2020, 322, 58-65.
[http://dx.doi.org/10.1016/j.toxlet.2020.01.006] [PMID: 31962155]
[76]
Satpute, R.M.; Bhutia, Y.D.; Lomash, V.; Bhattacharya, R. Efficacy assessment of co-treated alpha-ketoglutarate and N-acetyl cysteine against the subchronic toxicity of cyanide in rats. Toxicol. Ind. Health, 2019, 35(6), 410-423.
[http://dx.doi.org/10.1177/0748233719851902] [PMID: 31244408]
[77]
Calzetta, L.; Matera, M.G.; Rogliani, P.; Cazzola, M. Multifaceted activity of N-acetyl-l-cysteine in chronic obstructive pulmonary disease. Expert Rev. Respir. Med., 2018, 12(8), 693-708.
[http://dx.doi.org/10.1080/17476348.2018.1495562] [PMID: 29972340]
[78]
Vasdev, S.; Mian, T.; Longerich, L.; Prabhakaran, V.; Parai, S. N-acetyl cysteine attenuates ethanol induced hypertension in rats. Artery, 1995, 21(6), 312-316.
[PMID: 8833231]
[79]
Zalewska, A.; Szarmach, I.; Żendzian-Piotrowska, M.; Maciejczyk, M. The effect of N-acetylcysteine on respiratory enzymes, ADP/ATP ratio, glutathione metabolism, and nitrosative stress in the salivary gland mitochondria of insulin resistant rats. Nutrients, 2020, 12(2), 458.
[http://dx.doi.org/10.3390/nu12020458] [PMID: 32059375]
[80]
Charron, M.J.; Williams, L.; Seki, Y.; Du, X.Q.; Chaurasia, B.; Saghatelian, A.; Summers, S.A.; Katz, E.B.; Vuguin, P.M.; Reznik, S.E. Antioxidant effects of N-acetylcysteine prevent programmed metabolic disease in mice. Diabetes, 2020, 69(8), 1650-1661.
[http://dx.doi.org/10.2337/db19-1129] [PMID: 32444367]
[81]
Tabassum, R.; Jeong, N.Y.; Jung, J. Therapeutic importance of hydrogen sulfide in age-associated neurodegenerative diseases. Neural Regen. Res., 2020, 15(4), 653-662.
[http://dx.doi.org/10.4103/1673-5374.266911] [PMID: 31638087]
[82]
Sbodio, J.I.; Snyder, S.H.; Paul, B.D. Regulators of the transsulfuration pathway. Br. J. Pharmacol., 2019, 176(4), 583-593.
[http://dx.doi.org/10.1111/bph.14446] [PMID: 30007014]
[83]
Smith, A.D.; Refsum, H. Homocysteine - from disease biomarker to disease prevention. J. Intern. Med., 2021, 290(4), 826-854.
[http://dx.doi.org/10.1111/joim.13279] [PMID: 33660358]
[84]
Liampas, I.; Siokas, V.; Mentis, A.A.; Aloizou, A.M.; Dastamani, M.; Tsouris, Z.; Aslanidou, P.; Brotis, A.; Dardiotis, E. Serum homocysteine, pyridoxine, folate, and vitamin b12 levels in migraine: systematic review and meta-analysis. Headache, 2020, 60(8), 1508-1534.
[http://dx.doi.org/10.1111/head.13892] [PMID: 32615014]
[85]
Kamat, P.K.; Mallonee, C.J.; George, A.K.; Tyagi, S.C.; Tyagi, N. Homocysteine, alcoholism, and its potential epigenetic mechanism. Alcohol. Clin. Exp. Res., 2016, 40(12), 2474-2481.
[http://dx.doi.org/10.1111/acer.13234] [PMID: 27805256]
[86]
Schurr, A.; West, C.A.; Heine, M.F.; Rigor, B.M. The neurotoxicity of sulfur-containing amino acids in energy-deprived rat hippocampal slices. Brain Res., 1993, 601(1-2), 317-320.
[http://dx.doi.org/10.1016/0006-8993(93)91728-B] [PMID: 8431779]
[87]
Piubelli, L.; Murtas, G.; Rabattoni, V.; Pollegioni, L. The role of D-amino acids in Alzheimer’s disease. J. Alzheimers Dis., 2021, 80(2), 475-492.
[http://dx.doi.org/10.3233/JAD-201217] [PMID: 33554911]
[88]
Janáky, R.; Varga, V.; Hermann, A.; Saransaari, P.; Oja, S.S. Mechanisms of L-cysteine neurotoxicity. Neurochem. Res., 2000, 25(9-10), 1397-1405.
[http://dx.doi.org/10.1023/A:1007616817499] [PMID: 11059810]
[89]
Puka-Sundvall, M.; Eriksson, P.; Nilsson, M.; Sandberg, M.; Lehmann, A. Neurotoxicity of cysteine: Interaction with glutamate. Brain Res., 1995, 705(1-2), 65-70.
[http://dx.doi.org/10.1016/0006-8993(95)01139-0] [PMID: 8821734]
[90]
Rishitha, N.; Muthuraman, A.; Saravanababu, C. Therapeutic evaluation of thymoquinone in the intracerebroventricular injection of l-cysteine induced vascular dementia in rats. Int. J. Nutr. Pharmacol. Neurol. Dis., 2020, 10(3), 120.
[91]
Emrani, S.; Lamar, M.; Price, C.C.; Wasserman, V.; Matusz, E.; Au, R.; Swenson, R.; Nagele, R.; Heilman, K.M.; Libon, D.J. Alzheimer’s/vascular spectrum dementia: Classification in addition to diagnosis. J. Alzheimers Dis., 2020, 73(1), 63-71.
[http://dx.doi.org/10.3233/JAD-190654] [PMID: 31815693]
[92]
Hansen, K.B.; Yi, F.; Perszyk, R.E.; Furukawa, H.; Wollmuth, L.P.; Gibb, A.J.; Traynelis, S.F. Structure, function, and allosteric modulation of NMDA receptors. J. Gen. Physiol., 2018, 150(8), 1081-1105.
[http://dx.doi.org/10.1085/jgp.201812032] [PMID: 30037851]
[93]
Elshorbagy, A.K.; Church, C.; Valdivia-Garcia, M.; Smith, A.D.; Refsum, H.; Cox, R. Dietary cystine level affects metabolic rate and glycaemic control in adult mice. J. Nutr. Biochem., 2012, 23(4), 332-340.
[http://dx.doi.org/10.1016/j.jnutbio.2010.12.009] [PMID: 21543215]
[94]
Hughes, C.E.; Coody, T.K.; Jeong, M.Y.; Berg, J.A.; Winge, D.R.; Hughes, A.L. Cysteine toxicity drives age-related mitochondrial decline by altering iron homeostasis. Cell, 2020, 180(2), 296-310.e18.
[http://dx.doi.org/10.1016/j.cell.2019.12.035] [PMID: 31978346]
[95]
Safieh, M.; Korczyn, A.D.; Michaelson, D.M. ApoE4: an emerging therapeutic target for Alzheimer’s disease. BMC Med., 2019, 17(1), 64.
[http://dx.doi.org/10.1186/s12916-019-1299-4] [PMID: 30890171]
[96]
Todkar, K.; Ilamathi, H.S.; Germain, M. Mitochondria and lysosomes: Discovering bonds. Front. Cell Dev. Biol., 2017, 5, 106.
[http://dx.doi.org/10.3389/fcell.2017.00106] [PMID: 29270406]
[97]
Lawrence, R.E.; Zoncu, R. The lysosome as a cellular centre for signalling, metabolism and quality control. Nat. Cell Biol., 2019, 21(2), 133-142.
[http://dx.doi.org/10.1038/s41556-018-0244-7] [PMID: 30602725]
[98]
Liang, L.P.; Patel, M. Plasma cysteine/cystine redox couple disruption in animal models of temporal lobe epilepsy. Redox Biol., 2016, 9, 45-49.
[http://dx.doi.org/10.1016/j.redox.2016.05.004] [PMID: 27285054]
[99]
Patsoukis, N.; Zervoudakis, G.; Georgiou, C.D.; Angelatou, F.; Matsokis, N.A.; Panagopoulos, N.T. Thiol redox state and lipid and protein oxidation in the mouse striatum after pentylenetetrazol-induced epileptic seizure. Epilepsia, 2005, 46(8), 1205-1211.
[http://dx.doi.org/10.1111/j.1528-1167.2005.63704.x] [PMID: 16060929]
[100]
Liang, L.P.; Patel, M. Seizure-induced changes in mitochondrial redox status. Free Radic. Biol. Med., 2006, 40(2), 316-322.
[http://dx.doi.org/10.1016/j.freeradbiomed.2005.08.026] [PMID: 16413413]
[101]
Zhu, J.W.; Yuan, J.F.; Yang, H.M.; Wang, S.T.; Zhang, C.G.; Sun, L.L.; Yang, H.; Zhang, H. Extracellular cysteine (Cys)/cystine (CySS) redox regulates metabotropic glutamate receptor 5 activity. Biochimie, 2012, 94(3), 617-627.
[http://dx.doi.org/10.1016/j.biochi.2011.09.013] [PMID: 21964032]
[102]
Marković, A.R.; Hrnčić, D.; Macut, D.; Stanojlović, O.; Djuric, D. Anticonvulsive effect of folic acid in homocysteine thiolactone-induced seizures. Cell. Mol. Neurobiol., 2011, 31(8), 1221-1228.
[http://dx.doi.org/10.1007/s10571-011-9724-z] [PMID: 21695479]
[103]
Lehotský, J.; Tothová, B.; Kovalská, M.; Dobrota, D.; Beňová, A.; Kalenská, D.; Kaplán, P. Role of homocysteine in the ischemic stroke and development of ischemic tolerance. Front. Neurosci., 2016, 10, 538.
[http://dx.doi.org/10.3389/fnins.2016.00538] [PMID: 27932944]
[104]
Sabetghadam, M.; Mazdeh, M.; Abolfathi, P.; Mohammadi, Y.; Mehrpooya, M. Evidence for a beneficial effect of oral N-acetylcysteine on functional outcomes and inflammatory biomarkers in patients with acute ischemic stroke. Neuropsychiatr. Dis. Treat., 2020, 16, 1265-1278.
[http://dx.doi.org/10.2147/NDT.S241497] [PMID: 32547030]
[105]
Coutts, S.B. Diagnosis and management of transient ischemic attack. Continuum (Minneap. Minn.), 2017, 23(1), 82-92.
[http://dx.doi.org/10.1212/CON.0000000000000424] [PMID: 28157745]
[106]
Slivka, A.; Cohen, G. Brain ischemia markedly elevates levels of the neurotoxic amino acid, cysteine. Brain Res., 1993, 608(1), 33-37.
[http://dx.doi.org/10.1016/0006-8993(93)90770-N] [PMID: 8495346]
[107]
Moretti, R.; Caruso, P. The controversial role of homocysteine in neurology: From labs to clinical practice. Int. J. Mol. Sci., 2019, 20(1), 231.
[http://dx.doi.org/10.3390/ijms20010231] [PMID: 30626145]
[108]
Hipólito, A.; Nunes, S.C.; Vicente, J.B.; Serpa, J. Cysteine aminotransferase (CAT): A pivotal sponsor in metabolic remodeling and an ally of 3-mercaptopyruvate sulfurtransferase (MST) in cancer. Molecules, 2020, 25(17), 3984.
[http://dx.doi.org/10.3390/molecules25173984] [PMID: 32882966]
[109]
Szabo, C.; Papapetropoulos, A. International union of basic and clinical pharmacology. CII: pharmacological modulation of H2S levels: H2S donors and H2S biosynthesis inhibitors. Pharmacol. Rev., 2017, 69(4), 497-564.
[http://dx.doi.org/10.1124/pr.117.014050] [PMID: 28978633]
[110]
Cui, T.; Liu, W.; Chen, S.; Yu, C.; Li, Y.; Zhang, J.Y. Antihypertensive effects of allicin on spontaneously hypertensive rats via vasorelaxation and hydrogen sulfide mechanisms. Biomed. Pharmacother., 2020, 128, 110240.
[http://dx.doi.org/10.1016/j.biopha.2020.110240] [PMID: 32480217]
[111]
Wang, Y.; Zhao, Z.; Shi, S.; Gao, F.; Wu, J.; Dong, S.; Zhang, W.; Liu, Y.; Zhong, X. Calcium sensing receptor initiating cystathionine-gamma-lyase/hydrogen sulfide pathway to inhibit platelet activation in hyperhomocysteinemia rat. Exp. Cell Res., 2017, 358(2), 171-181.
[http://dx.doi.org/10.1016/j.yexcr.2017.06.013] [PMID: 28633902]
[112]
Majumder, A.; Singh, M.; Behera, J.; Theilen, N.T.; George, A.K.; Tyagi, N.; Metreveli, N.; Tyagi, S.C. Hydrogen sulfide alleviates hyperhomocysteinemia-mediated skeletal muscle atrophy via mitigation of oxidative and endoplasmic reticulum stress injury. Am. J. Physiol. Cell Physiol., 2018, 315(5), C609-C622.
[http://dx.doi.org/10.1152/ajpcell.00147.2018] [PMID: 30110564]
[113]
Xin, D.; Chu, X.; Bai, X.; Ma, W.; Yuan, H.; Qiu, J.; Liu, C.; Li, T.; Zhou, X.; Chen, W.; Liu, D.; Wang, Z. l-Cysteine suppresses hypoxia-ischemia injury in neonatal mice by reducing glial activation, promoting autophagic flux and mediating synaptic modification via H2S formation. Brain Behav. Immun., 2018, 73, 222-234.
[http://dx.doi.org/10.1016/j.bbi.2018.05.007] [PMID: 29751053]
[114]
Grajeda-Iglesias, C.; Aviram, M. Specific amino acids affect cardiovascular diseases and atherogenesis via protection against macrophage foam cell formation: Review article. Rambam Maimonides Med. J., 2018, 9(3), e0022.
[http://dx.doi.org/10.5041/RMMJ.10337] [PMID: 29944113]
[115]
Koike, S.; Ogasawara, Y. Sulfur atom in its bound state is a unique element involved in physiological functions in mammals. Molecules, 2016, 21(12), 1753.
[http://dx.doi.org/10.3390/molecules21121753] [PMID: 28009842]
[116]
Kan, J.; Guo, W.; Huang, C.; Bao, G.; Zhu, Y.; Zhu, Y.Z. S-propargyl-cysteine, a novel water-soluble modulator of endogenous hydrogen sulfide, promotes angiogenesis through activation of signal transducer and activator of transcription 3. Antioxid. Redox Signal., 20l4, 20(15), 2303-2316.
[117]
Lin, J.; Lee, I.M.; Song, Y.; Cook, N.R.; Selhub, J.; Manson, J.E.; Buring, J.E.; Zhang, S.M. Plasma homocysteine and cysteine and risk of breast cancer in women. Cancer Res., 2010, 70(6), 2397-2405.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-3648] [PMID: 20197471]
[118]
Carnagarin, R.; Nolde, J.M.; Ward, N.C.; Lugo-Gavidia, L.M.; Chan, J.; Robinson, S.; Jose, A.; Joyson, A.; Azzam, O.; Galindo Kiuchi, M.; Mwipatayi, B.P.; Schlaich, M.P. Homocysteine predicts vascular target organ damage in hypertension and may serve as guidance for first-line antihypertensive therapy. J. Clin. Hypertens. (Greenwich), 2021, 23(7), 1380-1389.
[http://dx.doi.org/10.1111/jch.14265] [PMID: 34137162]
[119]
Lai, W.K.C.; Kan, M.Y. Homocysteine-induced endothelial dysfunction. Ann. Nutr. Metab., 2015, 67(1), 1-12.
[http://dx.doi.org/10.1159/000437098] [PMID: 26201664]
[120]
Khaledifar, A.; Mobasheri, M.; Kheiri, S.; Zamani, Z. Comparison of N-acetylcysteine and angiotensin converting enzyme inhibitors in blood pressure regulation in hypertensive patients. ARYA Atheroscler., 2015, 11(1), 5-13.
[PMID: 26089925]
[121]
Go, Y.M.; Jones, D.P. Cysteine/cystine redox signaling in cardiovascular disease. Free Radic. Biol. Med., 2011, 50(4), 495-509.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.11.029] [PMID: 21130865]
[122]
Altıparmak, I.H.; Erkuş, M.E.; Sezen, H.; Demirbag, R.; Gunebakmaz, O.; Kaya, Z.; Sezen, Y.; Asoglu, R.; Dedeoglu, I.H.; Neselioglu, S.; Erel, O. The relation of serum thiol levels and thiol/disulphide homeostasis with the severity of coronary artery disease. Kardiol. Pol., 2016, 74(11), 1346-1353.
[http://dx.doi.org/10.5603/KP.a2016.0085] [PMID: 27221962]
[123]
Kar, S.; Shahshahan, H.R.; Kambis, T.N.; Yadav, S.K.; Li, Z.; Lefer, D.J.; Mishra, P.K. Hydrogen sulfide ameliorates homocysteine-induced cardiac remodeling and dysfunction. Front. Physiol., 2019, 10, 598.
[http://dx.doi.org/10.3389/fphys.2019.00598] [PMID: 31178749]
[124]
Sun, H.J.; Wu, Z.Y.; Nie, X.W.; Bian, J.S. Role of endothelial dysfunction in cardiovascular diseases: The link between inflammation and hydrogen sulfide. Front. Pharmacol., 2020, 10, 1568.
[http://dx.doi.org/10.3389/fphar.2019.01568] [PMID: 32038245]
[125]
Elshorbagy, A.K.; Smith, A.D.; Kozich, V.; Refsum, H. Cysteine and obesity. Obesity (Silver Spring), 2012, 20(3), 473-481.
[http://dx.doi.org/10.1038/oby.2011.93] [PMID: 21546934]
[126]
Elshorbagy, A.K.; Valdivia-Garcia, M.; Refsum, H.; Butte, N. The association of cysteine with obesity, inflammatory cytokines and insulin resistance in Hispanic children and adolescents. PLoS One, 2012, 7(9), e44166.
[http://dx.doi.org/10.1371/journal.pone.0044166] [PMID: 22984471]
[127]
Stipanuk, M.H. Sulfur amino acid metabolism: Pathways for production and removal of homocysteine and cysteine. Annu. Rev. Nutr., 2004, 24, 539-577.
[http://dx.doi.org/10.1146/annurev.nutr.24.012003.132418] [PMID: 15189131]
[128]
Baker, D.H. Comparative species utilization and toxicity of sulfur amino acids. J. Nutr., 2006, 136(6), 1670S-1675S.
[http://dx.doi.org/10.1093/jn/136.6.1670S] [PMID: 16702338]
[129]
Bełtowski, J. Endogenous hydrogen sulfide in perivascular adipose tissue: Role in the regulation of vascular tone in physiology and pathology. Can. J. Physiol. Pharmacol., 2013, 91(11), 889-898.
[http://dx.doi.org/10.1139/cjpp-2013-0001] [PMID: 24117256]
[130]
Boden, G. Obesity, insulin resistance and free fatty acids. Curr. Opin. Endocrinol. Diabetes Obes., 2011, 18(2), 139-143.
[http://dx.doi.org/10.1097/MED.0b013e3283444b09] [PMID: 21297467]
[131]
Lee, P.D.K.; Conover, C.A.; Powell, D.R. Regulation and function of insulin-like growth factor-binding protein-1. Proc. Soc. Exp. Biol. Med., 1993, 204(1), 4-29.
[http://dx.doi.org/10.3181/00379727-204-43630] [PMID: 7690486]
[132]
Ruan, W.; Lai, M. Insulin-like growth factor binding protein: A possible marker for the metabolic syndrome? Acta Diabetol., 2010, 47(1), 5-14.
[http://dx.doi.org/10.1007/s00592-009-0142-3] [PMID: 19771387]
[133]
Takemoto, Y. Pressor response to L-cysteine injected into the cisterna magna of conscious rats involves recruitment of hypothalamic vasopressinergic neurons. Amino Acids, 2013, 44(3), 1053-1060.
[http://dx.doi.org/10.1007/s00726-012-1440-6] [PMID: 23239012]
[134]
McGavigan, A.K.; O’Hara, H.C.; Amin, A.; Kinsey-Jones, J.; Spreckley, E.; Alamshah, A.; Agahi, A.; Banks, K.; France, R.; Hyberg, G.; Wong, C.; Bewick, G.A.; Gardiner, J.V.; Lehmann, A.; Martin, N.M.; Ghatei, M.A.; Bloom, S.R.; Murphy, K.G. L- cysteine suppresses ghrelin and reduces appetite in rodents and humans. Int. J. Obes., 2015, 39(3), 447-455.
[http://dx.doi.org/10.1038/ijo.2014.172] [PMID: 25219528]
[135]
Glanville, N.T.; Anderson, G.H. Altered methionine metabolism in streptozotocin-diabetic rats. Diabetologia, 1984, 27(4), 468-471.
[http://dx.doi.org/10.1007/BF00273913] [PMID: 6391990]
[136]
Brosnan, J.T.; Man, K.C.; Hall, D.E.; Colbourne, S.A.; Brosnan, M.E. Interorgan metabolism of amino acids in streptozotocin-diabetic ketoacidotic rat. Am. J. Physiol., 1983, 244(2), E151-E158.
[PMID: 6401931]
[137]
Nakatsu, D.; Horiuchi, Y.; Kano, F.; Noguchi, Y.; Sugawara, T.; Takamoto, I.; Kubota, N.; Kadowaki, T.; Murata, M. L-cysteine reversibly inhibits glucose-induced biphasic insulin secretion and ATP production by inactivating PKM2. Proc. Natl. Acad. Sci. USA, 2015, 112(10), E1067-E1076.
[http://dx.doi.org/10.1073/pnas.1417197112] [PMID: 25713368]
[138]
Pan, Y.; Wang, W.; Huang, S.; Ni, W.; Wei, Z.; Cao, Y.; Yu, S.; Jia, Q.; Wu, Y.; Chai, C.; Zheng, Q.; Zhang, L.; Wang, A.; Sun, Z.; Huang, S.; Wang, S.; Chen, W.; Lu, Y. Beta-elemene inhibits breast cancer metastasis through blocking pyruvate kinase M2 dimerization and nuclear translocation. J. Cell. Mol. Med., 2019, 23(10), 6846-6858.
[http://dx.doi.org/10.1111/jcmm.14568] [PMID: 31343107]
[139]
Carter, R.N.; Morton, N.M. Cysteine and hydrogen sulphide in the regulation of metabolism: Insights from genetics and pharmacology. J. Pathol., 2016, 238(2), 321-332.
[http://dx.doi.org/10.1002/path.4659] [PMID: 26467985]
[140]
Zhang, Z.; Deng, X.; Liu, Y.; Liu, Y.; Sun, L.; Chen, F. PKM2, function and expression and regulation. Cell. Biosci., 2019, 9(1), 52.8.
[http://dx.doi.org/10.1186/s13578-019-0317-8]
[141]
Puckett, D.L.; Alquraishi, M.; Chowanadisai, W.; Bettaieb, A. The role of PKM2 in metabolic reprogramming: Insights into the regulatory roles of non-coding RNAs. Int. J. Mol. Sci., 2021, 22(3), 1171.
[http://dx.doi.org/10.3390/ijms22031171] [PMID: 33503959]
[142]
Kaneko, Y.; Kimura, Y.; Kimura, H.; Niki, I. L-cysteine inhibits insulin release from the pancreatic beta-cell: Possible involvement of metabolic production of hydrogen sulfide, a novel gasotransmitter. Diabetes, 2006, 55(5), 1391-1397.
[http://dx.doi.org/10.2337/db05-1082] [PMID: 16644696]
[143]
Yusuf, M.; Kwong Huat, B.T.; Hsu, A.; Whiteman, M.; Bhatia, M.; Moore, P.K. Streptozotocin-induced diabetes in the rat is associated with enhanced tissue hydrogen sulfide biosynthesis. Biochem. Biophys. Res. Commun., 2005, 333(4), 1146-1152.
[http://dx.doi.org/10.1016/j.bbrc.2005.06.021] [PMID: 15967410]
[144]
Kamboj, S.S.; Vasishta, R.K.; Sandhir, R. N-acetylcysteine inhibits hyperglycemia-induced oxidative stress and apoptosis markers in diabetic neuropathy. J. Neurochem., 2010, 112(1), 77-91.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06435.x] [PMID: 19840221]
[145]
Juster-Switlyk, K.; Smith, A.G. Updates in diabetic peripheral neuropathy. F1000 Res., 2016, 5, 738.
[http://dx.doi.org/10.12688/f1000research.7898.1] [PMID: 27158461]
[146]
Brings, S.; Fleming, T.; Freichel, M.; Muckenthaler, M.U.; Herzig, S.; Nawroth, P.P. Dicarbonyls and advanced glycation end-products in the development of diabetic complications and targets for intervention. Int. J. Mol. Sci., 2017, 18(5), 984.
[http://dx.doi.org/10.3390/ijms18050984] [PMID: 28475116]
[147]
Gibbons, C.H.; Goebel-Fabbri, A. Microvascular complications associated with rapid improvements in glycemic control in diabetes. Curr. Diab. Rep., 2017, 17(7), 48.
[http://dx.doi.org/10.1007/s11892-017-0880-5] [PMID: 28526993]
[148]
Watts, M.E.; Pocock, R.; Claudianos, C. Brain energy and oxygen metabolism: Emerging role in normal function and disease. Front. Mol. Neurosci., 2018, 11, 216.
[http://dx.doi.org/10.3389/fnmol.2018.00216] [PMID: 29988368]
[149]
Paramasivan, S.; Adav, S.S.; Ngan, S.C.; Dalan, R.; Leow, M.K.S.; Ho, H.H.; Sze, S.K. Serum albumin cysteine trioxidation is a potential oxidative stress biomarker of type 2 diabetes mellitus. Sci. Rep., 2020, 10(1), 6475.
[http://dx.doi.org/10.1038/s41598-020-62341-z] [PMID: 32296090]
[150]
Heidari, N.; Sajedi, F.; Mohammadi, Y.; Mirjalili, M.; Mehrpooya, M. Ameliorative effects of N-acetylcysteine as adjunct therapy on symptoms of painful diabetic neuropathy. J. Pain Res., 2019, 12, 3147-3159.
[http://dx.doi.org/10.2147/JPR.S228255] [PMID: 31819599]
[151]
Pugliese, N.R.; Fabiani, I.; Conte, L.; Nesti, L.; Masi, S.; Natali, A.; Colombo, P.C.; Pedrinelli, R.; Dini, F.L. Persistent congestion, renal dysfunction and inflammatory cytokines in acute heart failure: A prognosis study. J. Cardiovasc. Med. (Hagerstown), 2020, 21(7), 494-502.
[http://dx.doi.org/10.2459/JCM.0000000000000974] [PMID: 32487865]
[152]
Skogestad, J.; Aronsen, J.M. Hypokalemia-induced arrhythmias and heart failure: New insights and implications for therapy. Front. Physiol., 2018, 9, 1500.
[http://dx.doi.org/10.3389/fphys.2018.01500] [PMID: 30464746]
[153]
Burke, A.P.; Fonseca, V.; Kolodgie, F.; Zieske, A.; Fink, L.; Virmani, R. Increased serum homocysteine and sudden death resulting from coronary atherosclerosis with fibrous plaques. Arterioscler. Thromb. Vasc. Biol., 2002, 22(11), 1936-1941.
[http://dx.doi.org/10.1161/01.ATV.0000035405.16217.86] [PMID: 12426228]
[154]
Xu, R.; Tao, A.; Bai, Y.; Deng, Y.; Chen, G. Effectiveness of N-acetylcysteine for the prevention of contrast-induced nephropathy: A systematic review and meta-analysis of randomized controlled trials. J. Am. Heart Assoc., 2016, 5(9), e003968.
[http://dx.doi.org/10.1161/JAHA.116.003968] [PMID: 27663415]
[155]
Efrati, S.; Averbukh, M.; Berman, S.; Feldman, L.; Dishy, V.; Kachko, L.; Weissgarten, J.; Golik, A.; Averbukh, Z. N-Acetylcysteine ameliorates lithium-induced renal failure in rats. Nephrol. Dial. Transplant., 2005, 20(1), 65-70.
[http://dx.doi.org/10.1093/ndt/gfh573] [PMID: 15546888]
[156]
Romão, C.M.; Pereira, R.C.; Shimizu, M.H.M.; Furukawa, L.N.S. N-acetyl-l-cysteine exacerbates kidney dysfunction caused by a chronic high-sodium diet in renal ischemia and reperfusion rats. Life Sci., 2019, 231, 116544.
[http://dx.doi.org/10.1016/j.lfs.2019.116544] [PMID: 31181229]
[157]
Azzini, E.; Ruggeri, S.; Polito, A. Homocysteine: Its possible emerging role in at-risk population groups. Int. J. Mol. Sci., 2020, 21(4), 1421.
[http://dx.doi.org/10.3390/ijms21041421] [PMID: 32093165]
[158]
Wollesen, F.; Brattström, L.; Refsum, H.; Ueland, P.M.; Berglund, L.; Berne, C. Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus. Kidney Int., 1999, 55(3), 1028-1035.
[http://dx.doi.org/10.1046/j.1523-1755.1999.0550031028.x] [PMID: 10027940]
[159]
Larsson, S.C.; Håkansson, N.; Wolk, A. Dietary cysteine and other amino acids and stroke incidence in women. Stroke, 2015, 46(4), 922-926.
[http://dx.doi.org/10.1161/STROKEAHA.114.008022] [PMID: 25669310]
[160]
Hasanbasic, S.; Jahic, A.; Karahmet, E.; Sejranic, A.; Prnjavorac, B. The role of cysteine protease in Alzheimer disease. Mater. Sociomed., 2016, 28(3), 235-238.
[http://dx.doi.org/10.5455/msm.2016.28.235-238] [PMID: 27482169]
[161]
Bonifácio, V.D.B.; Pereira, S.A.; Serpa, J.; Vicente, J.B. Cysteine metabolic circuitries: druggable targets in cancer. Br. J. Cancer, 2021, 124(5), 862-879.
[http://dx.doi.org/10.1038/s41416-020-01156-1] [PMID: 33223534]
[162]
Siklos, M.; BenAissa, M.; Thatcher, G.R.J. Cysteine proteases as therapeutic targets: Does selectivity matter? A systematic review of calpain and cathepsin inhibitors. Acta Pharm. Sin. B, 2015, 5(6), 506-519.
[http://dx.doi.org/10.1016/j.apsb.2015.08.001] [PMID: 26713267]
[163]
Montine, T.J.; Picklo, M.J.; Amarnath, V.; Whetsell, W.O.J., Jr.; Graham, D.G. Neurotoxicity of endogenous cysteinylcatechols. Exp. Neurol., 1997, 148(1), 26-33.
[http://dx.doi.org/10.1006/exnr.1997.6662] [PMID: 9398447]
[164]
Sullivan, J.M.; Traynelis, S.F.; Chen, H.S.; Escobar, W.; Heinemann, S.F.; Lipton, S.A. Identification of two cysteine residues that are required for redox modulation of the NMDA subtype of glutamate receptor. Neuron, 1994, 13(4), 929-936.
[http://dx.doi.org/10.1016/0896-6273(94)90258-5] [PMID: 7524561]
[165]
Jain, S.K. L-cysteine supplementation as an adjuvant therapy for type-2 diabetes. Can. J. Physiol. Pharmacol., 2012, 90(8), 1061-1064.
[http://dx.doi.org/10.1139/y2012-087] [PMID: 22783875]
[166]
Haddad, M.; Hervé, V.; Ben Khedher, M.R.; Rabanel, J.M.; Ramassamy, C. Glutathione: An old and small molecule with great functions and new applications in the brain and in Alzheimer’s disease. Antioxid. Redox Signal., 2021, 35(4), 270-292.
[http://dx.doi.org/10.1089/ars.2020.8129] [PMID: 33637005]

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