Abstract
The goal of this review is to explored the therapeutic application of L-Arginine (L-ARG) against various pathological illnesses, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), cardiovascular disorder, mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes (MELAS), sickle cell anemia, tumour, epilepsy, erectile dysfunction therapy (ED), gestational hypertension (GH), and menopause issues. L-ARG is an important semi-essential alpha-amino acid that serves as a natural precursor for the synthesis of nitric oxide (NO). It is generally synthesized from proteinogenic amino acid proline through glutamine and glutamate. The degradation of L-ARG is a complex process due to the expression of multiple enzymes in the form of a substrate. The metabolism of L-ARG takes place in various multiple pathways, such as nitric oxide synthase, Arginine glycine amidinotransferase, and Arginine decarboxylase which results in the production of a diverse range of biochemical compounds, such as nitric oxide, polyamines, proline, glutamate, creanine, agmatine homoarginine, and urea. NO is a highly diffusible free radicle with a regulatory function in the heart and acts as an important vasodilator in intact endothelium. NO serves as an important neurotransmitter in the brain and a mediator of host defense in the immune system. L-ARG is also needed for ammonia detoxification, which is a very toxic chemical to the central nervous system. This review article focuses on the relevance of L-ARG in the prevention and treatment of a variety of illnesses.
Graphical Abstract
[http://dx.doi.org/10.1016/j.jcm.2016.06.002] [PMID: 27660594]
[http://dx.doi.org/10.1155/2018/7569127] [PMID: 29854093]
[http://dx.doi.org/10.1007/s00726-008-0210-y] [PMID: 19030957]
[http://dx.doi.org/10.1038/ki.1992.394] [PMID: 1280702]
[http://dx.doi.org/10.1016/j.ccr.2011.10.011] [PMID: 22523434]
[http://dx.doi.org/10.1111/j.1365-2125.2007.02990.x] [PMID: 17662090]
[http://dx.doi.org/10.1042/bj1850593] [PMID: 6248027]
[http://dx.doi.org/10.1093/jn/134.10.2743S] [PMID: 15465778]
[http://dx.doi.org/10.3389/fphys.2012.00218] [PMID: 22737132]
[http://dx.doi.org/10.1177/0148607112458325] [PMID: 22914893]
[http://dx.doi.org/10.1254/jjp.69.1] [PMID: 8847826]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09742] [PMID: 28760945]
[http://dx.doi.org/10.2174/1570159X15666171017102547] [PMID: 29046155]
[PMID: 19079617]
[http://dx.doi.org/10.1146/annurev-micro-090816-093247] [PMID: 28697669]
[http://dx.doi.org/10.1155/S1110724304402034] [PMID: 15467163]
[http://dx.doi.org/10.1002/cphy.c160011] [PMID: 28333380]
[http://dx.doi.org/10.1186/1742-2094-8-26] [PMID: 21439035]
[http://dx.doi.org/10.1007/s12264-013-1423-y] [PMID: 24664866]
[http://dx.doi.org/10.1016/j.redox.2017.10.014] [PMID: 29080524]
[http://dx.doi.org/10.1016/j.jphs.2016.07.001] [PMID: 27530818]
[http://dx.doi.org/10.1007/s007020050016] [PMID: 10847559]
[http://dx.doi.org/10.26402/jpp.2022.1.01] [PMID: 35639033]
[http://dx.doi.org/10.3390/cells11213520] [PMID: 36359916]
[http://dx.doi.org/10.1007/s12035-013-8517-4] [PMID: 23900742]
[PMID: 21623030]
[PMID: 26885338]
[http://dx.doi.org/10.1177/0960327118788139] [PMID: 30001633]
[http://dx.doi.org/10.1371/journal.pone.0235296]
[http://dx.doi.org/10.1371/journal.pone.0104643] [PMID: 25111602]
[http://dx.doi.org/10.1111/apha.12344] [PMID: 25041756]
[http://dx.doi.org/10.3390/nu8060364] [PMID: 27314383]
[http://dx.doi.org/10.1007/s13105-016-0480-x] [PMID: 27121159]
[http://dx.doi.org/10.1152/ajpheart.01086.2010] [PMID: 22610173]
[http://dx.doi.org/10.1113/jphysiol.2003.049478] [PMID: 14561818]
[http://dx.doi.org/10.1152/ajpheart.00785.2002] [PMID: 12609820]
[http://dx.doi.org/10.1089/152308603770379982] [PMID: 14588141] [http://dx.doi.org/10.3389/fchem.2020.00732] [PMID: 32974285]
[http://dx.doi.org/10.1016/s0891-5849(02)01111-5] [PMID: 12446202] [http://dx.doi.org/10.1152/ajpheart.00785.2002] [PMID: 12609820]
[http://dx.doi.org/10.3389/fphys.2015.00020] [PMID: 25741283]
[http://dx.doi.org/10.1016/j.ejphar.2015.10.046] [PMID: 26522927]
[http://dx.doi.org/10.1002/ana.410160409] [PMID: 6093682]
[http://dx.doi.org/10.1038/348651a0] [PMID: 2102678]
[http://dx.doi.org/10.1016/j.bbagen.2011.04.018] [PMID: 21600268]
[http://dx.doi.org/10.1212/01.WNL.0000151976.60624.01] [PMID: 15728297]
[http://dx.doi.org/10.1016/j.ymgme.2015.06.004] [PMID: 26095523]
[http://dx.doi.org/10.1177/2326409817697399]
[http://dx.doi.org/10.7759/cureus.32709] [PMID: 36686069]
[http://dx.doi.org/10.1002/pbc.22562] [PMID: 20582959]
[http://dx.doi.org/10.1016/j.pathophys.2015.05.001] [PMID: 26051155]
[http://dx.doi.org/10.1182/blood.2019003672] [PMID: 32384147]
[http://dx.doi.org/10.1016/j.cell.2016.09.031] [PMID: 27745970]
[http://dx.doi.org/10.1016/j.advms.2018.08.018] [PMID: 30605863]
[http://dx.doi.org/10.2174/138161210790232121] [PMID: 20236068]
[http://dx.doi.org/10.1111/cas.14490] [PMID: 32426941]
[http://dx.doi.org/10.1007/s13760-020-01467-3] [PMID: 33113107]
[http://dx.doi.org/10.1016/j.ejpn.2014.07.001] [PMID: 25127453]
[http://dx.doi.org/10.1016/j.ymgme.2016.04.015] [PMID: 27324284]
[http://dx.doi.org/10.1007/s11011-016-9933-8] [PMID: 27882480]
[http://dx.doi.org/10.1016/j.pharep.2014.06.013] [PMID: 25443724]
[http://dx.doi.org/10.1016/j.biopha.2018.09.093] [PMID: 30253372]
[http://dx.doi.org/10.5772/intechopen.78288]
[http://dx.doi.org/10.3389/fphar.2020.582155] [PMID: 33542686]
[http://dx.doi.org/10.1111/andr.12293] [PMID: 28178400]
[http://dx.doi.org/10.1016/j.jsxm.2018.12.002] [PMID: 30770070]
[http://dx.doi.org/10.1517/14656566.2.1.95] [PMID: 11336572]
[http://dx.doi.org/10.1111/j.1442-2042.2007.01973.x] [PMID: 18269446]
[http://dx.doi.org/10.1016/j.cca.2017.10.007] [PMID: 29024618]
[http://dx.doi.org/10.3164/jcbn.14-104] [PMID: 26236104]
[http://dx.doi.org/10.1080/10641950601147994] [PMID: 17454224]
[http://dx.doi.org/10.1177/1470320313475910] [PMID: 23435582]
[http://dx.doi.org/10.1113/JP273331] [PMID: 28090634]
[http://dx.doi.org/10.1016/0002-9378(93)90301-X] [PMID: 8238202]
[http://dx.doi.org/10.1016/j.maturitas.2014.10.002] [PMID: 25456263]
[http://dx.doi.org/10.1016/S0735-1097(99)00553-7] [PMID: 10676669]
[http://dx.doi.org/10.14814/phy2.13409] [PMID: 28904082]
[http://dx.doi.org/10.1111/j.1475-097X.2008.00809.x] [PMID: 18510549]
[PMID: 15002538]
[http://dx.doi.org/10.1359/JBMR.041121] [PMID: 15746992]
[http://dx.doi.org/10.1016/j.bbrc.2014.10.029] [PMID: 25445598]
[http://dx.doi.org/10.1161/01.CIR.94.2.130] [PMID: 8674170]
[http://dx.doi.org/10.1086/689289] [PMID: 28680568]
[http://dx.doi.org/10.1007/s00726-016-2245-9] [PMID: 27156062]
[http://dx.doi.org/10.3390/ijms21051865] [PMID: 32182846]
[http://dx.doi.org/10.1159/000499037] [PMID: 30947169]
[http://dx.doi.org/10.1080/13543776.2019.1567711]
[http://dx.doi.org/10.1039/D0TB00498G] [PMID: 32496488]
[http://dx.doi.org/10.1097/01.CCM.0000278600.14265.95] [PMID: 17713411]
[http://dx.doi.org/10.1093/jn/138.10.2021S] [PMID: 18806118]
[http://dx.doi.org/10.1152/physrev.00037.2016] [PMID: 29412048]
[http://dx.doi.org/10.1007/s40268-020-00318-z] [PMID: 32720006]
[http://dx.doi.org/10.1007/s00726-018-02687-x] [PMID: 30604097]
[http://dx.doi.org/10.4103/2277-9175.166138] [PMID: 26601090]
[http://dx.doi.org/10.1371/journal.pone.0094448] [PMID: 24736629]
[http://dx.doi.org/10.5604/20831862.1111436] [PMID: 25177096]
[http://dx.doi.org/10.1038/ajh.2009.57] [PMID: 19300425]
[http://dx.doi.org/10.1159/000030454] [PMID: 10743698]
[http://dx.doi.org/10.1093/jn/134.10.2801S] [PMID: 15465789]
[http://dx.doi.org/10.1007/s13224-016-0853-7] [PMID: 27651617]
[http://dx.doi.org/10.1007/s007260170028] [PMID: 11665817]
[http://dx.doi.org/10.1093/jn/134.10.2807S] [PMID: 15465790]
[http://dx.doi.org/10.1007/s11010-005-1810-4] [PMID: 15786711]
[http://dx.doi.org/10.1016/j.intimp.2023.109853] [PMID: 36827919]
[http://dx.doi.org/10.1080/14767058.2023.2217465] [PMID: 37258415]
[http://dx.doi.org/10.1186/s12933-023-01827-2] [PMID: 36609317]
[http://dx.doi.org/10.3390/nu14050961] [PMID: 35267936]
[http://dx.doi.org/10.2174/1389203717666160627074017] [PMID: 27356939]
[http://dx.doi.org/10.1016/j.bbrc.2019.05.044] [PMID: 31101333]
[http://dx.doi.org/10.1016/j.bbrc.2020.04.158] [PMID: 32423812]
[http://dx.doi.org/10.1007/s00726-012-1341-8] [PMID: 22714012]
[http://dx.doi.org/10.1007/s00394-017-1548-2] [PMID: 29052766]
[http://dx.doi.org/10.1155/2020/4291327] [PMID: 32090093]
[http://dx.doi.org/10.1016/S0300-9084(00)01192-5] [PMID: 11368855]
[http://dx.doi.org/10.1002/cbf.1766] [PMID: 21638297]
[http://dx.doi.org/10.12688/f1000research.5877.1] [PMID: 28751963]
[http://dx.doi.org/10.5812/cardiovascmed.29419] [PMID: 26889456]
[http://dx.doi.org/10.1177/0883073899014001021] [PMID: 10593560]
[http://dx.doi.org/10.1016/S0378-4347(01)00100-1] [PMID: 11482732]
[http://dx.doi.org/10.1007/s00431-003-1177-z] [PMID: 12684898]
[http://dx.doi.org/10.1172/JCI111640] [PMID: 6511918]
[http://dx.doi.org/10.1186/1750-1172-7-32] [PMID: 22642880]