CHANGES IN GLUTATHIONE AND GLUTATHIONE REDUCTASE POSITIONING GLUTATHIONE-S-TRANSFERASE AS A FUNCTION OF CELL CONCENTRATION WITH ENZYME ACTIVITIES FOUND TO INFLUENCE BEHAVIOR.

Glutathione reductase (GSR, GR) locus in the chromosomal region 8p21.1, (EC 1.8.1.7)-(§, ‡) is a protein-S-glutathionylation, as a (human) Mitochondrial localization of hGSR and its associated enzymes cellular thiol/disulfides S-Glutathione reductase (GSR) which is the importance of significance in reversible thiol modifications which  regenerates reduced glutathione (GSH) and GSSG to the reduced form found in the obvious structural properties of glutathione reductase. The redox regulating enzymes relationship with TTase (thioltransferase) activity with the ratio of the activities of G3PD, as the mechanism (of cellular repair) 'differs' (gssg-g6pg) according to the type of reducing glutathionylated mixed disulfide, including protein-S-S-glutathione (PSSG), GSR reduces (PSSG) modified by thiolation to a normal level in human lens epithelial (HLE) cells. This may have implications in stress- and aging-related pathologies in astrocytes and granule cells, demonstrated by comparable mitochondria/cytosolic concentrations of its thiol proteins, where a mitochondrial leader sequence (cDNA) is present in the gene structure of human GSR and may be the Cytoplasmic Isoform (derivative or inhibitor formed) of  mitochondrial dysfunction that contains the catalytic cysteine revealing a possible therapeutic strategy/target, also indicating transiently accumulated inhibitor proteins modified by thiolation (cysteine catalytic subunits) compounds that inhibit these (re)activation processes (hGSR) with its structure-based prosthetic group (FAD) cofactor is common because of the levels of cysteine available; are mitochondria/cytosolic concentrations that the Glutathione reductases reversible thiol modifications which catalyzes the reduction of GSSG to GSH the natural GR substrate is dependent on the NADPH:GS-SG ratio.
Cys58 and Cys63 represent the enzyme's results seen as the reductive (GSH) Cys-58 and oxidative (GSSG) Cys-63 is the relationship of these two enzymes, His467' is seen to interact with Cys63 more optimally and Cys-58 produces the second GSH intermediate molecule of the reaction is the reduced glutathione-to-oxidized glutathione ratio (GSH/GS-SG) when compared to the substrate free form correlated with (FAD) the flavin compounds, flow from NADPH to the substrate GSSG via flavin. The reducing equivalents needed for regeneration of GSH are provided by NADPH. The enzyme has affinity for flavin adenine dinucleotide (FAD) the prosthetic group of GR, and maintains high levels of reduced glutathione  (Cytoplasmic Isoform: Produced by alternative initiation of isoform Mitochondrial homodimer, derivative or inhibitor formed from the GSR Pyridine, dimerisation domain.) in the cytosol. Glutathione reductase (GR) plays a key role in maintaining either a thiol group or a nonprotein sulfhydryl group (NPS) form of GSH, and potential for thioredoxin and glutathione systems, as thioredoxin dose not require GSH and GR for catalytic activity. Glutathione reductase (GR) utilizes NADPH produced by G6PDH (glucose-6-phosphate dehydrogenase) enzyme activities, and enzyme glutathione reductase (GR) represents the erythrocyte glutathione-reducing system (GRS), of the GSH pathway to oxidation and inactivation in the activity of GSH peroxidase and GSH reductase. Expression of the regulatory subunit of gamma-glutamylcysteine synthetase/ligase (GCL) catalyzes the first and rate-limiting step in the production of the cellular (GSH) glutathione. Dietary riboflavin (Vitamin B2) intake produces its active essential coenzyme flavin forms, riboflavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) of glutathione reductase (GR), or the GR activity correlated with red-cell flavin compounds.When both GSSG and NADP(+) substrates and products are present, glutathione reductase (GR) is a enzyme required for the conversion in the presence and absence of flavin adenine dinucleotide (FAD), glutathione reductase (GR) is an obligatory FAD-containing homodimer. GSSG via glutathione reductase (GR) regenerates reduced glutathione which is essential for antioxidant defense. The flavoenzyme glutathione reductase (GR) reduces 'oxidized glutathione' (GSSG) back to GSH, also involving glutamate-cysteine ligase and modulatory (GCL)-can be upregulated ∉ as the cellular GSH system, indicating short-term and heritable tolerance of exposure to oxidative stress from/via numerous reporting ∈ mechanisms. NADPH is used by glutathione reductase for the reduction of oxidized glutathione (glutathione disulphide) GSSG to GSH-dependent peroxide metabolism. 4-Hydroxynonenal (HNE) is one of the major end products of lipid peroxidation which may lead to enhanced action of  the (GSR) oxygen radical, glutathione S-transferases (GSTs) are specifically suited to the detoxification and removal of 4-HNE (∋ or ∝) from cells which may provide a basis for selective cellular and/or subcellular distribution of mitochondrial and cytosolic to individual detoxifying gene inducer activities of glutathione reductase (GR), the cellular (GSH) glutathione. It was evident the enzyme glutathione reductase (GR) represents the erythrocyte glutathione-reducing system (GRS), of the GSH pathway to oxidation and the (∉ or ∝) inhibition constant for reversible inactivation in the activity of glutathione related antioxidant enzymes. And GSH reductase may be one of the factors that remained in focus that suggests its effects on the antioxidant system related to glutathione synthesis (GCL), degradation, and functions.

Biological Xenobiotics, Extracts, Applications of note In the presence of Glutathione reductase.:

Schisandrin (Schisandra chinensis), used in traditional Chinese medicine. PMID:21328628

Transketolase (TK) and transaldolase (TA)

Melatonin PMID:15571523, 19475625

Blackberry (Rubus sp.) cultivars, The 'Hull Thornless',  PMID:11087537

Glutathione dehydrogenase (ascorbate)-[dehydroascorbate reductase (DHAR), and glutathione reductase (GR). This enzyme participates in the glutathione metabolism the active metabolite of vitamin D3 increases glutathione levels.] PMID:11087537, 23770363

3H-1,2-dithiole-3-thione nutraceutical D3T potently induces the cellular GSH system, Anethole trithione is a drug used in the treatment of dry mouth, the Anethole trithione isomer is related to anethole (anise camphor) used as a flavoring substance. PMID:17206382*, 19408115,     19176875*, 15896789, 18408143*,

16946404*

Cassia fistula used in herbal medicine. PMID:19088944

Sanguinarine is extracted from some plants, including bloodroot and Mexican prickly poppy (Argemone mexicana) where argimone oil causes Epidemic dropsy. PMID:11260782

Vitamin E, PMID: 15672860

Tocotrienols are natural compounds members of the vitamin E family found in select vegetable oils are an essential nutrient for the body. PMID:21845802

Pyrrolizidine alkaloids are produced by plants as a defense mechanism against insect herbivores consumption of PAs is known as pyrrolizidine alkaloidosis. PMID:20144959

Apple extract (AE) PMID:20401791

Lipoic Acid an organic compound, forming a disulfide bond, available as a dietary supplement PMID:15246746, 21073761

Carnitine PMID:15246746, 10581232

Vitamin D upregulated expression of GCLC and GR. PMID:23770363

Vitamin D3_ PMID:12416023

Vitamin E_ PMID:10459841, 8360018, 18296478, 21845802, 15490422, 16885600, 7062348, 20729758, 21086752

Shidagonglao roots Mahonia fortunei (十大功劳 shi da gong lao) species contains the alkaloid berberine PMID:199382 18

Coenzyme Q10 (CoQ10) PMID:16621054

Trigonella foenum graecum seed powder (TSP) PMID:15026271

Boschniakia rossica, a ̱̱̱Traditional Chinese medicine. PMID:19352025

Aegle marmelos commonly known as bael is a species of tree. PMID:18830880

Scoparia dulcis A medicinal plant, dulcis. PMID:21905284

Fenugreek (Trigonella foenum-graecum)  is used as a herb. PMID:15026271

L-arginine (L-Arg) semiessential supplementation common natural amino acid. PMID:16038634

Hypericum perforatum (St. John's Wort) PMID:18754092

Urtica dioica often called common nettle PMID:12834006

Usnea longissima, a medicinal lichen. PMID:16169175

Capparis decidua, a fruting tree also used in folk medicine and herbalism. PMID:22272107

Indole-3-carbinol found at relatively high levels in cruciferous vegetables such as broccoli

PMID:9512722, 14512388

Ascorbate Vitamin C. PMID:14512388

Sulforaphane It is obtained from cruciferous vegetables such as broccoli. PMID:12628444, 18607771*, 22303412

Andrographis paniculata, may shorten the duration and lessen the symptoms of common cold. PMID:11507728

Vitamin B-1 (thiamine) PMID:1132146, 10450194, 21308351*, 11514662*, 1270885

Vitamin B2 (riboflavin) PMID: 5822598, 5550591, 1201246, 5794396, 237845, 3677785, 3582603, 12194936, 2721660, 1261528, 5721130, 14608016, 4400882, 7883462, 844948, 7337797, 5881,12641409, 4393763, 3497609, 16883966...(№ 1244, OMIM.138300)

Vitamin B-6 (Pyridoxine) PMID:2721660, 3582603, 10450194, 15490422, 1270885, 7417521, 7337797, 7814235

Vitamin B9 (Folic acid)  PMID: 844947, 1270885

Aspartate transaminase (AST) or glutamic oxaloacetic transaminase (GOT) catalyzes the interconversion of aspartate an important enzyme in amino acid metabolism. PMID:1132146, 10450194, 1253408

β-Carotene is a strongly colored red-orange pigment abundant in plants and fruits. PMID:19957244

3-Hydroxykynurenine (3OHKyn) a metabolite of tryptophan. PMID:11273669

Ajoene ((E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), a garlic-derived natural compound. PMID:9986706 PDB: 1BWC

Propolis a product made by bees. PMID:19394397

Resveratrol produced naturally by several plants PMID:12797471
 No CiTO relationships defined:
 http://vixra.org/abs/1506.0104
 http://www.citeulike.org/user/emissrto/article/13645622

Catalase, the antioxidant heme enzyme one of three subgroups related to catalase deficiency in humans modulating the normal catalase reaction dependent on NADPH-binding catalases for function.

Catalase (CAT) is converted by decomposition and intracellular localization relationships of the main cellular antioxidant enzyme system like superoxide dismutase (SOD), peroxiredoxins (Prdx), and glutathione peroxidase (GPX) are peroxisomal matrix enzymes in the cytoplasm, translocated to the peroxisomes to catalyze hydrogen peroxide H2O2 which is decomposed to oxygen and water, locus: 11p13 (§, ‡). Unlike catalase, the objective of this communication, SOD which prevents the formation of Hydroxyl radicals - (HRGT) determined from constant of O2.- dismutation, and generation of reversibly inactive (CAT)-compound II, Panax ginseng could induce both transcription factors. Catalase is  composed of four identical subunits each of the subunits binds one heme-containing active site, and produces two catalase compounds HPI and HPII (PDB: 1p80) is flipped 180 degrees » with respect to the orientation of the heme related to the « root mean square to the structure of catalase, (Mutation Location) from peroxisomal catalases inactive state in compound II NADP+(H) binding pockets inverted remains similar to the structure of the wild type (Val111, PDB:1A4E, KatG) orientation on the heme proximal (PDB: 1GGK) side, inactivate catalase can be prevented by melatonin. Catalase (CAT; EC 1.11.1.6) a  free radical scavenging enzyme (FRSE) is a scavenger of H2O2. Protoporphyrin - (ZnPPIX) (PDB: 1H6N), from a heme group of the 'heme-pathway, which forms catalase,' is a scavenger of antioxidant (HO-1-HMOX1) heme oxygenase, involving ROS. Catalase is part of the enzymatic defense system constituting the primary defense against ROS, zinc protoporphyrin IX (ZnPPIX) is an inhibitor of (HO-1) heme oxygenase. Catalase protects the cell from oxidative damage by the accumulation of cellular reactive oxygen species (ROS) generation systems, those peroxisomal enzymes that breaks down hydrogen peroxide after H(2)O(2) exposure, and thereby mitigates* (some contradictory* results) the toxic effects of hydrogen peroxide. In the process (The typical hydroperoxidases (CAT) known as Compound I) of the substrate of catalase, NADP+ (an inactive state, compound II) is replaced by another molecule of NADP(H) to provide protection of catalase against inactivation by (H2O2) hydrogen peroxide. Erythrocyte  [Human erythrocyte catalase (HEC), The NADPH-binding sites were empty - PDB: 1F4J, 1QQW] and plasma indices (enzymatic-antioxidants) initially implies the thiobarbituric acid-reacting substances (TBARS) based on reaction with hydroxyl radicals (OH) can release thiobarbituric acid, TBAR inhibition measures malondialdehyde (MDA - impact of coenzyme Q10) correlated (with MPO-myeloperoxidase activity -generating ROS) as co-variable, by which mulberry leaf polysaccharide (MLPII) via the decomposition of (certain) MDA, products of lipid peroxidation (LPO) were reduced. Comparisons were to specific activities of catalase (SNP) single nucleotide polymorphisms (CAT-C-262 (rs1001179) the low-risk allele) of genetic variants in both, promoter a common C/T polymorphism (262-C/T), and in nine - exonic - regions and its boundaries, occur frequently associated distally in genomic mutations, similar to those of normal catalase demonstrating changes in catalase protein level targeted to the peroxisomal matrix. The 262-C/T CAT low-risk allele is hypothetically related to the lower risk variant allele CAT Tyr308 G to A point mutation ineducable in the Japanese acatalasemia allele. The common C/T polymorphism can be targeted by dietary and/or pharmacological antioxidants, and the endogenous antioxidant defense enzymes concentration can prevent cellular lipid (LPO) peroxidative reactions occurring. Catalase is a homotetramer complex of 4 identical monofunctional subunits. Catalase is located at the peroxisome of human cells associated with several (PBDs)-peroxisomal biogenesis disorders commonly caused by mutations in the PEX genes, peroxisomal targeting signal 1 (PTS1) protein affecting in peroxisomal biogenesis, the monomeric to homotetrameric transition in the forms of peroxisome biogenesis disorder. PBDs also include Acatalasemia the only disease known to be caused by the (CAT) gene. In human catalase, the antioxidant heme enzyme, is localized in the cytoplasm to the peroxisome, nucleus, or linked with mitochondria which in most cells lack catalase (Peroxisomes do not contain DNA), its mitochondrial fraction (microperoxisome), a secondary phenomena shows physiological decline, aging and age-related reactions in mitochondrial function and disfunction. NADPH is required for the prevention of forming an inactive state of the enzyme. Antioxidative defence mechanisms, capacity and redox cycle enzyme activities increasing with Tc treatment Tinospora cordifolia (Tc), T and B cells and antibody. Both RBCs and plasma were measured on parameters of oxidative stress. Syzygium cumini aqueous leaves extract (ASc) was able to remove oxidant species in a hyperglycemic state generated in red blood cells RBC-CAT levels. Catalase alone is unable to prevent in a hyperglycemic state. Macrophages recruit other types of immune cells such as lymphocytes white blood cells (WBCs).  Catalase is dependent on the family of NADPH-binding catalases for function, the prevention and reversal of inactivation by its toxic substrate (H2O2) hydrogen peroxide. Amyloid-beta binds catalase and inhibits (H2O2) hydrogen peroxide, a reactive oxygen species, breakdown through efficient dismutation, and malonaldelhyde (MDA) determined in plasma, as well as another member of the oxidoreductase family, myeloperoxidase (MPO (EC 1.11.1.7)) converting H(2)O(2), the reducing equivalents produces (HOCl) hypochlorous acid a mechanism of cell-mediated antimicrobial immune defense for monofunctional catalases one of three subgroups related to catalase deficiency in humans, in micro-organisms manganese-containing catalases ('large catalases') determining in part the bifunctional activity of (KatG, PDB:1X7U) represented by bifunctional (heme) catalase-peroxidase based Bacterial-resistance mechanisms. Peroxiredoxins (Prxs, EC 1.11.1.21), bifunctional catalase-peroxidases (KatGs) two organelle systems are antioxidant enzymes of the peroxiredoxin family that oxidize and reduce H(2)O(2) hydrogen peroxide thereby modulating the catalase reaction, KatGs are not found in plants and animals. Trx (thioredoxin) a redox-regulating protein also controls the antioxidant enzyme activity of the main cellular antioxidant enzymes (AOE) superoxide dismutase (SOD) and catalase.

The function of NADPH bound to Catalase.
The cytosine to thymidine transition of nucleotide-262 (-262C>T) Computer analysis indicated that the two variants bound promoter the Ile  (-262 C/T) and (B) Ile-262 in the 5'-flanking region carrying the T allele best captured and characterized the generation of the hydroxyl radical site in (PDB: 1DGB), (CAT) -[GLU] 330C>T transition, is known also as -262C>T. The 'T allele in comparison to the C allele' is a common C/T polymorphism frequency in the promoter region association was observed between genotypes for locus11p13 risk alleles acatalasemia mutation Asp (37C>T in exon 9) was hypothetically related to the lower risk Japanese acatalasemia allele Tyr308 a single G to A (see: rs7947841  to evaluate the link to rs769214) point mutation ineducable or near exon 9 (TC, CC, TT) of the CAT gene to which variant changes in the promoter region C/T-262 polymorphism are more closely related to CAT T/C at codon 389 in exon 9 (rs769217) polymorphism did not differ significantly from those of healthy controls in both promoter (-262 C/T) and in exonic (ASP-389 C/T) regions of the catalase (CAT).  Tyr 370 resolves the 25 A-long (hydrogen peroxide) channel a constriction or narrowing of the channel leading to the heme cavity ('Parameters) situated in the entrance channel to a heme protoporphyrin (ZnPPIX) (PDB: 1H6N) from a heme group, capable of heme biosynthesis' in a wide range of organisms convert it into into heme b, protoporphyrin IX-heme. Two channels lead close to the distal side.  A third channel reaching the heme proximal side Tyr 370, Ile-262 is proposed as a the 'PDB: 1DGB - variant with a substituted residue in the ASP 178 to the (Met) D181E variant PDB 1p80'.  These differences include the structure of the variant protein Val111Ala (Saccharomyces cerevisiae) related supports the existence of the 'Heme and NADP(H) binding pockets'. The omission of a 20-residue  PDB: 1F4J, (1QQW) segment corresponds to the N-terminal (blue) of catalase from human erythrocytes (HEC), or in a C-terminal (red) domain organized with an extra flavodoxin-like fold topology may provide with weak coordination the N- or C-terminal, that allows scrutiny of the origins (topology) in this report of what would otherwise remain speculative or determined with further verification.

 Biological Xenobiotic Extracts Applications of note In the presence of Catalase:

green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG)

Yamamoto T, Lewis J, Wataha J, Dickinson D, Singh B, Bollag WB, Ueta E, OsakiT, Athar M, Schuster G, Hsu S. Roles of catalase and hydrogen peroxide in greentea polyphenol-induced chemopreventive effects. J Pharmacol Exp Ther. 2004Jan;308(1):317-23. Epub 2003 Oct 20. PubMed PMID: 14569057.Furukawa A, Oikawa S, Murata M, Hiraku Y, Kawanishi S. (-)-Epigallocatechingallate causes oxidative damage to isolated and cellular DNA. Biochem Pharmacol.2003 Nov 1;66(9):1769-78. PubMed PMID: 14563487.*

Trigonella (Fenugreek)

Mohammad S, Taha A, Bamezai RN, Basir SF, Baquer NZ. Lower doses of vanadatein combination with trigonella restore altered carbohydrate metabolism andantioxidant status in alloxan-diabetic rats. Clin Chim Acta. 2004Apr;342(1-2):105-14. Erratum in: Clin Chim Acta. 2010 Aug 5;411(15-16):1158.Mohamad, Sameer [corrected to Mohammad, Sameer]. PubMed PMID: 15026271.

Aegle marmelos

Khan TH, Sultana S. Antioxidant and hepatoprotective potential of Aeglemarmelos Correa. against CCl4-induced oxidative stress and early tumor events. JEnzyme Inhib Med Chem. 2009 Apr;24(2):320-7. doi: 10.1080/14756360802167754 .PubMed PMID: 18830880.

Centella asiatica
Flora SJ, Gupta R. Beneficial effects of Centella asiatica aqueous extractagainst arsenic-induced oxidative stress and essential metal status in rats.Phytother Res. 2007 Oct;21(10):980-8. PubMed PMID: 17600859.

Daidzein
Mishra P, Kar A, Kale RK. Prevention of chemically induced mammarytumorigenesis by daidzein in pre-pubertal rats: the role of peroxidative damageand antioxidative enzymes. Mol Cell Biochem. 2009 May;325(1-2):149-57. doi:10.1007/s11010-009-0029-1. Epub 2009 Feb 13. PubMed PMID: 19214712.

Capparis
Yadav P, Sarkar S, Bhatnagar D. Action of capparis decidua againstalloxan-induced oxidative stress and diabetes in rat tissues. Pharmacol Res. 1997Sep;36(3):221-8. PubMed PMID: 9367667.

Retinal
 Kannan R, Jin M, Gamulescu MA, Hinton DR. Ceramide-induced apoptosis: role ofcatalase and hepatocyte growth factor. Free Radic Biol Med. 2004 Jul15;37(2):166-75. PubMed PMID: 15203188.

Retinol
Cemek M, Caksen H, Bayiroğlu F, Cemek F, Dede S. Oxidative stress andenzymic-non-enzymic antioxidant responses in children with acute pneumonia. CellBiochem Funct. 2006 May-Jun;24(3):269-73. PubMed PMID: 16634091.

Diallyl disulfide (Allicin)
Kalayarasan S, Prabhu PN, Sriram N, Manikandan R, Arumugam M, Sudhandiran G.Diallyl sulfide enhances antioxidants and inhibits inflammation through theactivation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar rats. EurJ Pharmacol. 2009 Mar 15;606(1-3):162-71. doi: 10.1016/j.ejphar.2008.12.055. Epub2009 Jan 19. PubMed PMID: 19374873.

Leucas aspera (Catechin, EGCG)
Kripa KG, Chamundeeswari D, Thanka J, Uma Maheswara Reddy C. Modulation ofinflammatory markers by the ethanolic extract of Leucas aspera in adjuvantarthritis. J Ethnopharmacol. 2011 Apr 12;134(3):1024-7. doi:10.1016/j.jep.2011.01.010. Epub 2011 Jan 18. PubMed PMID: 21251972.

Urtica dioica (nettle suppliment)Ozen T, Korkmaz H. Modulatory effect of Urtica dioica L. (Urticaceae) leaf
extract on biotransformation enzyme systems, antioxidant enzymes, lactatedehydrogenase and lipid peroxidation in mice. Phytomedicine. 2003;10(5):405-15.PubMed PMID: 12834006.

Justicia adhatoda
Singh RP, Padmavathi B, Rao AR. Modulatory influence of Adhatoda vesica(Justicia adhatoda) leaf extract on the enzymes of xenobiotic metabolism,antioxidant status and lipid peroxidation in mice. Mol Cell Biochem. 2000Oct;213(1-2):99-109. PubMed PMID: 11129964.

Phyllanthus niruri L. (Euphorbiaceae) (P. niruri)
Bhattacharjee R, Sil PC. Protein isolate from the herb, Phyllanthus niruri L.(Euphorbiaceae), plays hepatoprotective role against carbon tetrachloride inducedliver damage via its antioxidant properties. Food Chem Toxicol. 2007May;45(5):817-26. Epub 2006 Nov 11. PubMed PMID: 17175085.

Tinospora cordifolia
Sharma V, Pandey D. Protective Role of Tinospora cordifolia againstLead-induced Hepatotoxicity. Toxicol Int. 2010 Jan;17(1):12-7. doi:10.4103/0971-6580.68343. PubMed PMID: 21042467; PubMed Central PMCID: PMC2964743.

Aher V, Kumar Wahi A. Biotechnological Approach to Evaluate theImmunomodulatory Activity of Ethanolic Extract of Tinospora cordifolia Stem(Mango Plant Climber). Iran J Pharm Res. 2012 Summer;11(3):863-72. PubMed PMID:24250513; PubMed Central PMCID: PMC3813135.

coenzyme Q10
Lee BJ, Lin YC, Huang YC, Ko YW, Hsia S, Lin PT. The relationship betweencoenzyme Q10, oxidative stress, and antioxidant enzymes activities and coronaryartery disease. ScientificWorldJournal. 2012;2012:792756. doi:10.1100/2012/792756. Epub 2012 May 3. PubMed PMID: 22645453; PubMed CentralPMCID: PMC3356738.

Dietary carotenoid-rich pequi oil
Miranda-Vilela AL, Akimoto AK, Alves PC, Pereira LC, Gonçalves CA,Klautau-Guimarães MN, Grisolia CK. Dietary carotenoid-rich pequi oil reducesplasma lipid peroxidation and DNA damage in runners and evidence for anassociation with MnSOD genetic variant -Val9Ala. Genet Mol Res. 2009 Dec15;8(4):1481-95. doi: 10.4238/vol8-4gmr684. PubMed PMID: 20082261.

Tinospora cordifolia  (Mango Plant Climber) extract from Tinospora known as Tinofend Aher V, Kumar Wahi A. Biotechnological Approach to Evaluate theImmunomodulatory Activity of Ethanolic Extract of Tinospora cordifolia Stem(Mango Plant Climber). Iran J Pharm Res. 2012 Summer;11(3):863-72. PubMed PMID:24250513; PubMed Central PMCID: PMC3813135.

 mulberry leaf polysaccharide (MLPII)
Ren C, Zhang Y, Cui W, Lu G, Wang Y, Gao H, Huang L, Mu Z. A polysaccharideextract of mulberry leaf ameliorates hepatic glucose metabolism and insulinsignaling in rats with type 2 diabetes induced by high fat-diet andstreptozotocin. Int J Biol Macromol. 2014 Oct 11. pii: S0141-8130(14)00674-6.doi: 10.1016/j.ijbiomac.2014.09.060. [Epub ahead of print] PubMed PMID: 25316427.

five widely studied medicinal plants (Protandim)
Nelson SK, Bose SK, Grunwald GK, Myhill P, McCord JM. The induction of humansuperoxide dismutase and catalase in vivo: a fundamentally new approach toantioxidant therapy. Free Radic Biol Med. 2006 Jan 15;40(2):341-7. PubMed PMID:16413416.

melatonin
Mayo JC, Tan DX, Sainz RM, Lopez-Burillo S, Reiter RJ. Oxidative damage tocatalase induced by peroxyl radicals: functional protection by melatonin andother antioxidants. Free Radic Res. 2003 May;37(5):543-53. PubMed PMID: 12797476.

Protective effect of harmaline
Kim DH, Jang YY, Han ES, Lee CS. Protective effect of harmaline and harmalolagainst dopamine- and 6-hydroxydopamine-induced oxidative damage of brainmitochondria and synaptosomes, and viability loss of PC12 cells. Eur J Neurosci.2001 May;13(10):1861-72. PubMed PMID: 11403679.

horseradish peroxidase (HRP)
Shen L, Hu N. Heme protein films with polyamidoamine dendrimer: directelectrochemistry and electrocatalysis. Biochim Biophys Acta. 2004 Jan30;1608(1):23-33. PubMed PMID: 14741582.

Selegiline (--)Deprenyl
Kitani K, Minami C, Isobe K, Maehara K, Kanai S, Ivy GO, Carrillo MC. Why(--)deprenyl prolongs survivals of experimental animals: increase of anti-oxidantenzymes in brain and other body tissues as well as mobilization of varioushumoral factors may lead to systemic anti-aging effects. Mech Ageing Dev. 2002Apr 30;123(8):1087-100. Review. PubMed PMID: 12044958.

Rhodiola rosea
Bayliak MM, Lushchak VI. The golden root, Rhodiola rosea, prolongs lifespanbut decreases oxidative stress resistance in yeast Saccharomyces cerevisiae.Phytomedicine. 2011 Nov 15;18(14):1262-8. doi: 10.1016/j.phymed.2011.06.010. Epub2011 Jul 30. PubMed PMID: 21802922.

Carnitine
Kiziltunc A, Coğalgil S, Cerrahoğlu L. Carnitine and antioxidants levels inpatients with rheumatoid arthritis. Scand J Rheumatol. 1998;27(6):441-5. PubMedPMID: 9855215.

 Syzygium cumini

 De Bona KS, Bellé LP, Sari MH, Thomé G, Schetinger MR, Morsch VM, Boligon A,
Athayde ML, Pigatto AS, Moretto MB. Syzygium cumini extract decrease adenosine
deaminase, 5'nucleotidase activities and oxidative damage in platelets of
diabetic patients. Cell Physiol Biochem. 2010;26(4-5):729-38. doi:
10.1159/000322340. Epub 2010 Oct 29. PubMed PMID: 21063110.

Gluathione peroxidase (GSH-Px1-GPX1) a extracellular selenoenzyme expression modulates xenobiotic metabolising enzymes.

     Glutathione peroxidase (EC 1.11.1.9) protects against oxidative damage via the chemoprotective action of nitric-oxide mediated lipid peroxidation and anti oxidative defense by gluathione (GSH-Px1-GPX1) a extracellular selenoenzyme, extracellular glutathione peroxidase (E-GPx) and cellular (C-GPx) detoxifies hydroperoxides. Other antioxidant genes (AOX) as Gpx1, is located in the cytosol and in (mt) mitochondria. Epithelial antioxidative enzymes (AOEs) are activities of GSH-Px1 (gluathione peroxidase), (SOD) superoxide dismutase, and thioredoxine reductase (TXNRD1) by itself or with thioredoxin (Trx) are antioxidant enzymes. Glutaredoxin (Grx) are reduced by the oxidation of glutathione an antioxidant, (The effect of iridoid  glucosides such as oleuropein an antioxidant, can often be bound to glucose.) phenolic compound isothiocyanate sulforaphane found in olive leaf, increased cell-lysate NAD(P)H:quinone oxidoreductase (NQO1) phase II activities reduction reactions, catalyzed such as by glutathione-S-transferase (GST) can catalyze the conjugation back to the thiol group and other GPx mimics (converted into selenocysteine), to the reaction site of glutathione (GSH) and antioxidants, implying (GR) reduction reactions back to glutathione, are an evolutionary relationship between GST and GPx/glutathione system defense in oxidative stress. "Glutathione" peroxidase (Gpx) content, and glutathione reductase (GR) components compose the glutathione (GSH) system, this contains Selenocysteine (Sec), the 21st amino acid at the active GPX site (Homo sapiens chromosome 3, GRCh37 primary reference: rs644261)- TGA  => UGA (selenocysteine, which occurs at the active site of  glutathione peroxidase GPX1 is coded by UGA, isoform 1 NM_201397.1-variant 1 represents the shorter transcript that  encodes the longer isoform 1, as compared to isoform 2- NM_000581.2 variant 2); (rs1050450) is intronless and has a shorter C-terminus. They represent the cDNA as a molecular mechanism (TGA) for down-regulation of mRNA expression and transcriptional code is a regulatory switch at the translational-step delivered to the ribosome in genes similar to Glutathione peroxidase 1 (GP, Gpx1, GSHPX1): locus 3p13-q12 (§, ‡,). GSH-Px is an essential nutrient selenium dependent GPX, by which mRNA translational repression of selenium-binding protein (SBP1) is accomplished when GPX1 increased in human plasma, if selenium-deficient, while independent of Se values in leukocyte (White blood cells) from correspondingly damaged DNA. In fibroblast activity, GPx1 was effective through the prevention or repair of DNA damage. The reductive detoxification of peroxides in cells modulates xenobiotic metabolising enzymes via anticarcinogen supplementation, e.g. selenium-yeast  in human plasma. GPX in turn, can lead to carcinogenesis. The heterozygote has an intraerythrocytic environment (red blood cell) with the favorable higher peroxidase activities role in malarial resistance. An in-frame GCG trinucleotide repeat was homozygous for the pseudogene GPX1 Pro197Leu-like two alleles associated with 6 GCG repeats coding for a polyalanine tract. CuZn-SOD (copper/zinc-superoxide dismutase) and other oxidoreductases contribute to the cellular defenses, repair of oxidative damage to DNA. Chronic hyperglycemia (excessive blood sugar) causes oxidative stress, 'Extract silymarin and Berberine-'may' overcome insulin resistance. And for diabetes Astragalus membranaceus  can improve the protective effect, an extract from Shidagonglao roots (Mahonia fortunei)  or the effects of Berberine from the main alkaloid of Coptis chinensis  are agents for preventing sepsis and its lipopolysaccharide (LPS) complications in human microvascular endothelial cells. GPX is down-regulated and peroxiredoxin (PRX) is up-regulated. Both use thioredoxin (Gpx and Prx, suppress Trx, a cysteine-based thioredoxin-specific GPx-Txn expression.) to recharge after reducing hydrogen peroxide (H2O2) along with other cellular molecules. Also found in transcripts in ocular tissues from oxidative anterior damaged cells,  GSH-dependent recombinant human lens thioltransferase (RHLT)* being  its repair systems. GPX1 could supress staurosporine-induced late generation of ROS, corresponding to reduction in visual loss.  Its role in pathogenesis of  (inflammatory disorders of blood antioxidant enzyme system) as an autoimmune disease background, appears to be the hydroperoxide metabolism in diverse pathogens*, an enzyme by single administration streptozotocin  (60 mg/kg) of negative implication, oxidative damage or antioxidant status when examined in contrast as metabolic syndrome through the GPX down-regulation are comparable, with reduced-enzyme-activity to the T allele of the GPx-1 genetic leucine/proline polymorphism at codon 198  approximately 70% for pro197 and 30% for leu197 named Pro198Leu (rs1050450). The leucine-containing allele was less responsive to GPx-1 enzyme activity. Thioltransferase (TTase) with GPx the dethiolating enzyme, thiol* catalysis glutaredoxin thioltransferase (Grx) content and activity to the thiol status produced by the oxidation of glutathione: a seleno-organic compound ebselen  (2-phenyl-1,2-benzisoselenazol-3(2H)-one) catalyzed in vitro, has been reported to '« mimic » development of small-molecule selenium compounds' ('synthetic antioxidant' GPX)  required for, a diphenyl diselenide PhSe group 'in the catalytic activities' is introduced by reaction (a monocyte-derived soluble protein (M-DSP/Gpx1) with 5-LO, (5-lipoxygenase ) activity this 'recovered (M-DSP)-GPx inactivation'. In which Serum Malondialdehyde (MDA) a marker (oxidative activity) generated from, reactive oxygen species (ROS) is thought to cause DNA damage with various antioxidants usually homeostatically controlled by endogenous superoxide dismutase (SOD), as a by-product and the oxygen-sensor neuroglobin (Nb), GSHPx reactive neurons or in brief neuronal damage (apoptosis) after ischemia. Antioxidant enzymes such as Cu/Zn-superoxide dismutase (SOD) and a 21-kD protein (involved in neuroprotection) GPx1 both in the free radical chain, protects neurons and Microglial cells. Microglial cells are, sensitive to small changes from Reactive oxygen species (ROS), free radical scavenging enzymes-mediated apoptosis. Neuronal loss and deteriorating CNS function: is linked to the pentose phosphate shunt, the (PPP) pentose phosphate pathway, has a relatively low content of enzymatic antioxidants, in a higher cellular ROS level to oxidative stress. A candidate (SePP1) selenoprotein (P-plasma) or  genetic variations homologous to GPX1 are rapidly degraded at relative low selenium concentrations. Microsomal (reconstituted fraction) glutathione transferase-1 (hGSTP1) decreased cytotoxicity ( cartilage degradation and regeneration [Leucas aspera] to mitochondria damage, directed to citrulline- containing proteins) by effects of hydrogen peroxide 'H(2)O(2), which causes lipid peroxidation (LPO) in the (ER) endoplasmic reticulum. In which LPO product Malondialdehyde and other Thiobarbituric acid reactive substances - TBARS - are formed as a byproduct, when the effects of GPX1 ( glutathione peroxidase 1)' is measured, the effects of Centella asiatica  extract detoxifies. Antioxidants and detoxication agents as antigenotoxic* agents (isoflavones via dietary intake) were also observed as cytogenetic end-points* of carcinogenesis. Over-expression could drain the  reduced glutathione ( hepatic and GSH dependent enzymes), cellular glutathione (GSH) levels, GSH acts as a feedback rate-limiting inhibitor of its synthesizing enzyme GCL (gamma-glutamyl-cysteine synthetase) activity,  Diosgenin  is a useful Marker degradation-compound of Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) against oxidation. The compound buthionine sulfoximine (BSO) inhibits the first step of glutathione synthesis, concerning the mechanism of GSH depletion. Gpx suppresses (thioredoxin) Trx - expression, which augments Anti-clastogenic (mutagenic agents), potential DNA-binding (heritable multigenerational/evolutionary tolerance), in a cDNA open reading frame (ORF) GPx1 is a small inversion (~pericentric), incorporating the co-translational selenocysteine which may be unique to the insertion sequence elements.

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      Biological Assembly GPx-1 tetrameric structure with an altered carcinogen metabolism and reduce oxygen tension to explain the anti-carcinogenic effects, the redox donor (hTXN-oxidoreductase Figure 4) status  (Figure 2) of one oxygen atom limited to only two regions may carry missense variant (rasmol_php_C and _D) a reaction incorporated into the overall tetrameric structures instability potentially in humans through modulation of biosynthetic and genetically modified GSH enzymes binding the selenocysteine insertion sequence elements. The specific activity of the enzyme Sec suggest how the molecular pathway might work, as the glutathione pathway may influence the enzyme Sec reaction site incorporation sequence in the 3'-untranslated region UTR of glutathione (GSH) may further reveal a signaling pathway that is activated. The differing and interacting roles of GPX1 and (Sec.) Selenocysteine Synthase [doi: 10.2210/rcsb_pdb/mom_2008_8] both vectorstogether with glutathione (HUMAN GLUTATHIONE TRANSFERASE (HGST) PDB ID: 1LJR ligand component GSH: C10 H17 N3 O6 S, molecules colored: aquamarine) did; activates two multiple signaling pathways in one of the Gpx1 variants 1 or 2 nucleotide, the nonsense codon, UGA has both, related to the antioxidative pathway vectors together PDB ID: 1gp1 (2-AMINO-3-SELENINO-PROPIONIC ACID: ALANINE  molecule colored: purple), is located near the selenocysteine insertion sequence element PDB ID: 2F8A (rainbow colored: ribbons) mutant of  GPX1. Interrogation of data based on experimentally determined models are limited but revealed network structures that dynamically conveyed information from the antioxidant enzymes that share a common pathway considered most important in the selenocysteine synthesis pathway from the information suggested, and they implicate at least one selenoprotein (GPx-1) in the process.