Tag Archives: TRXR

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.
PDB Id: 3DK9 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*, Glutathione reductase
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:


Brenneman, M. R.
Changes in glutathione and glutathione reductase
positioning glutathione-s-transferase as a function of cell concentration
with enzyme activities found to influence behavior. (2015).
URL http://vixra.org/abs/1506.0104.

http://www.citeulike.org/user/emissrto/article/13645622

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Thioredoxin reductase: Selenotetrapeptide sequences with specificity for thioredoxin and glutathione systems

  Thioredoxin reductase (EC 1.6.4.5) TXNRD1 (Alternate Symbols: GRIM-12, TR, TRXR) chromosomal position 12q23.3-q24.1 (§, ) is a homodimeric selenocysteine-containing enzyme. Secys a selenocysteine residue is an essential TR isozyme component, located near the C-terminus region [cysteine (Cys)-497,Secys-498] of the intracellular, redox cellular environments center in the catalytically active enzyme site, Gly-499 is the actual C-terminal amino acid. In their N-terminal sequences Cys-59, Cys-64 links the thiol/disulfide oxidoreductase dependent pathway reductases from there to the flexible C-terminal part (Secys) of the other sub cellular subunit by which Selenocystine is efficiently reduced and induce RNR (Ribonucleotide reductase) for replication and repair, where Trx reductase (TR) or oxidized GSH (GSSG) reductase further supply electrons for RNR. The protein reversibly modulates specific signal transduction cascades, to regulate multiple downstream intracellular redox-sensitive proteins that links NADPH and thiol-dependent processes which catalyzes NADPH-dependent reduction in the presence of the redox protein-Trx and thioredoxin reductase (TR) maintain cysteine residues in numerous proteins in the reduced state. There are three TXNRD selenoproteins  5-prime end variants essential for mammals, one V3 (TXNRD1) encodes an N-terminal glutaredoxin (GRX) these variants code for thioredoxin glutathione reductases (TGR). V3 associates with and triggers formation of Filopodia (cytoplasmic filaments) can guide actin in migrating cells, the emerging protrusions of cell membrane restructuring involved is in ‘deglutathionylation values” for mitochondrial and cytosolic thioredoxin reductase (TR) domains. Characterization of the TR native Thioredoxin and glutathione systems (TGR) suggests that the lifecycle of E. granulosus and Schistosoma mansoni a phylum of Platyhelmintha, involves the TXNRD1_v3 isoform containing a fused (Grx) glutaredoxin domain which is abolished by deglutathionylation’ targeted to either mitochondria or the nucleus in the reduction of glutathionylated substrates, in leishmaniasis (disease) glutathione reductase system (TGR) is replaced by the trypanothione reductase (TcTR) system in mammalian cells, essential as these TR3 are significant as a recognized drug target of these (TcTR) human protozoan parasites. Cytosolic TR1, mitochondrialTR3 and TrxR2 (locus 22q11.21) where TrxR1 and TrxR2 are consdered as the respective cytosolic 1w1e MITOCHONDRIAL cytoplasmicand mitochondrial thioredoxin reductases, plus the thioredoxin glutathione reductases-TGR systems most likely can reduce (Trx) by fusion of the TR and an N-terminal glutaredoxin domains. As a pyridine nucleotide disulfide oxidoreductase of the oxidized GSH and GSSG (selenodiglutathione) reductase TGR structures enzyme stability, are linked to the previously characterized two thioredoxin reductases cytosolic TR1 and TR3, and one mitochondrial variant. Selenols are key metabolites at mammalian TXNRD1’s active (SeCys 498) site. Thioredoxin undergoes NADPH-dependent reduction (NTRs) and reduce oxidized cysteine groups on mitochondrial TXNRD1 proteins similar to the cytosolic enzyme, from the FAD binding domain where the active cystines and the NADPH binding domain are contained, plus an interface domain (ID) of the C-terminal interface homologous to glutathione reductase identifies a mechanism of p53 mediated cell death regulation involving (TrxR) enzymes of redox homeostasis reactions to overcome the oxidative stress generating reactive oxygen species (ROS) on a complex combination of decreased apoptosis to prevent permanent cell damage and cell death that tumor cells use to evade the redox-sensitive signaling factors, or resistance to therapy. End products of lipid-peroxidation, 4-HNE-(4-Hydroxynonenal) can induce oxidative stress, other isoforms are more water-soluble adducts detoxifying such a buildup,  peroxidation might be limiting their (selenoproteins) proper expression. Thioredoxin reductase (TrxR) is the homodimeric flavoenzyme that catalyzes reduction of thioredoxin disulfide (Trx) one of the major redox control systems, involving a second interaction between NAD(P)H and/or (quinone reductase) NQO1 via the FAD-containing enzyme (TR), thioredoxin reductase forms an oxidoreductase system. TrxRs are able to reduce a number of substrate proteins other than Trx.


3qfbThe 3′ UTR of selenocysteine-containing genes have a common stem-loop structure, the sec insertion sequence (selenocystine-SECIS, PDB: 2ZZ0), that is necessary for the recognition of a catalytically active Sec codon rather in the values for mitochondrial and cytosolic thioredoxins reductase (TR) domains. The Sec residue is protonated at a different pka than in comparison to that of Cysteine. Cys59-Cys64 two cysteines pair also was oxidized in the N-terminal FAD domain essential for thioredoxin-reducing activity, and the need for Sec-498 (PDB: 2J3N) to be in complex with the FAD and NADP(+) during catalysis to the N-terminal active site cysteine residues Cys59-Cys64 and from there to the C-terminal part of the other subunit which have selenotetrapeptide sequences from the other module (PDB: 2J3N). Secys498 forms, (Human PDB 3QFB,) can both be identified at active site of the enzyme Gly-499 of the subunits active Cys-497-TRXR1 (the TR1 structure PDB: 3QFB) are the mechanism(s) for the incorporation of Se into TrxRs as the amino acid selenocysteine (Sec), as well as for delivery to a variety of secondary substrates or TRX (PDB: 3QFB) in nuclei provide means to quantify glutathione (GSH) (PDB: 3H8Q) conditions of the active GRX functonally and structurally analogus to TGR (selenodiglutathione) reductase. These two were modeled parts of TGR were linked to V3 (_TXNRD1) encodes an N-terminal inter-specific glutaredoxin (PDB: 1JHB).3qfb-3h8q From the FAD binding domain-(PDB: 1ZKQ ) active cystines and the NADPH binding domain where they are contained, plus an interface domain (ID) of the C-terminal ID in complex with its substrate thioredoxin (Trx-PDB: 1TRX, TXNRD1-3QFB) bringing Cys32 in Trx1 close to Cys497 in 3H8Q to quantify glutathione (GSH) that helped in characterizing  what was separately modeled as the Thioredoxin reductase (TXNRD1) domain which are consdered as the respective cytosolic and mitochondrial thioredoxin reductases units with a model obeying standard geometry that is conceivable of human thioredoxin reductase 1-2 and 3’s structures glutaredoxin domain 3H8Q  in complex with the FAD and NADP(H) when replaced by the TcTR (PDB: 2W0H) trypanothione/trypanothione reductase system involves a phylum of Platyhelmintha, where a glutathione (GSH) isoform containing a fused (Grx) glutaredoxin domain  (PDB: 1JHB) is essential for the parasite survival.  The intricate substrate specificities for the thioredoxin (Trx) system which consists of native Trx and the respective cytosolic  mitochondrial thioredoxin reductase (TrxR) enzymes are likely to be of central importance to these observations as a determinant of TrxR function in general, each (the thioredoxin reductase/thioredoxin pathway) can reduce a number of different types of substrates or cross-reactive-bound enzyme fractions as active with thioredoxin.
[1.] Selenium yeast: seleno yeast PMID: 16857846
[2.] Sulforaphane From Broccoli PMID: 16377050, 12742546, 20204301, 12949356, 19595745, 17150329, 15740016, 12663510, 15998110, 17300148
[3.] Chlorella vulgaris: corresponding to a chloroplast NADPH-dependent thioredoxin reductase gene (NTR-C), in Chlorella PMID: 18029787
[4.] Scutellarin:  It can be found in Scutellaria barbata and S. lateriflora. PMID: 15131321
[5.] Curcumin (TURMERIC plant of the ginger family): PMID: 21782934, 20160040, ~15879598
[6.] Experiments in E. huxleyi genus phytoplankton PMID: 20032866
[7.] Gambogic Acid pigment of gambooge resin from tree species Garcinia gummi-gutta. PMID: 24407164
[8.] Shikonin an antioxidant (no longer approved for use,: targets the Sec residue [13.] in TrxR1 to inhibit its physiological function. see: (Methane-) methylseleninic acid (MSA)) obtained from the extracts of  plant [9.] Lithospermum erythrorhizon. PMID: 24583460
[10.] Black tea extract (BTE) theaflavin (TF) PMID: 19059456
[11.] Green tea extract-epigallocatechin-3-gallate (EGCG) PMID: 19020731
[12.] Eicosatetraenoic acid, (Mortierella Alpina Oil) Arachidonic acid (AA) all-cis-5,8,11,14-eicosatetraenoic acid, 5-Hydroxyicosatetraenoic_acid_and_5-oxo-eicosatetraenoic_acid PMID: 15123685
[13.] Juglone: In the food industry known as C.I. Natural Brown 7 and C.I. 75500. (DTNB assay, a synthetic approach for Cys and Sec residues.) PMID: 21172426, 11170645, 18382651 … a 5,5′-[dithiobis Pyritinol: analogue, Sulbutiamine]
[14.] The antioxidant ubiquinol-10 (Q10) PMID: 12435734
[15.] Rottlerin, conductance potassium channel (BKCa++) opener, source the Kamala tree. PMID: 17581112
[16.] Ajoene a chemical compound available from garlic. PMID: 9986706
No CiTO relationships defined