Glutathione

Glutathione[1]
Names
Preferred IUPAC name
(2S)-2-Amino-5-({(2R)-1-[(carboxymethyl)amino]-1-oxo-3-sulfanylpropan-2-yl}amino)-5-oxopentanoic acid
Other names
γ-L-Glutamyl-L-cysteinylglycine
(2S)-2-Amino-4-({(1R)-1-[(carboxymethyl)carbamoyl]-2-sulfanylethyl}carbamoyl)butanoic acid
Identifiers
3D model (JSmol)
Abbreviations GSH
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.660
IUPHAR/BPS
KEGG
MeSH Glutathione
UNII
CompTox Dashboard (EPA)
  • InChI=1S/C10H17N3O6S/c11-5(10(18)19)1-2-7(14)13-6(4-20)9(17)12-3-8(15)16/h5-6,20H,1-4,11H2,(H,12,17)(H,13,14)(H,15,16)(H,18,19)/t5-,6-/m0/s1 Y
    Key: RWSXRVCMGQZWBV-WDSKDSINSA-N Y
  • C(CC(=O)N[C@@H](CS)C(=O)NCC(=O)O)[C@@H](C(=O)O)N
Properties
C10H17N3O6S
Molar mass 307.32 g·mol−1
Melting point 195 °C (383 °F; 468 K)[1]
Freely soluble[1]
Solubility in methanol, diethyl ether Insoluble[1]
Pharmacology
V03AB32 (WHO)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Y verify (what is YN ?)
Infobox references

Glutathione (GSH, /ˌɡluːtəˈθaɪoʊn/) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides, and heavy metals.[2] It is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side chain and cysteine. The carboxyl group of the cysteine residue is attached by normal peptide linkage to glycine.

Biosynthesis and occurrence

Glutathione biosynthesis involves two adenosine triphosphate-dependent steps:

  • First, γ-glutamylcysteine is synthesized from L-glutamate and cysteine. This conversion requires the enzyme glutamate–cysteine ligase (GCL, glutamate cysteine synthase). This reaction is the rate-limiting step in glutathione synthesis.[3]
  • Second, glycine is added to the C-terminal of γ-glutamylcysteine. This condensation is catalyzed by glutathione synthetase.

While all animal cells are capable of synthesizing glutathione, glutathione synthesis in the liver has been shown to be essential. GCLC knockout mice die within a month of birth due to the absence of hepatic GSH synthesis.[4][5]

The unusual gamma amide linkage in glutathione protects it from hydrolysis by peptidases.[6]

Occurrence

Glutathione is the most abundant thiol in animal cells, ranging from 0.5 to 10 mmol/L. It is present in the cytosol and the organelles.[6]

Human beings synthesize glutathione, but a few eukaryotes do not, including some members of Fabaceae, Entamoeba, and Giardia. The only known archaea that make glutathione are halobacteria. Some bacteria, such as "Cyanobacteria" and Pseudomonadota, can biosynthesize glutathione.[7][8]

Biochemical function

Glutathione exists in reduced (GSH) and oxidized (GSSG) states. The ratio of reduced glutathione to oxidized glutathione within cells is a measure of cellular oxidative stress[9][10] where increased GSSG-to-GSH ratio is indicative of greater oxidative stress. In healthy cells and tissue, more than 90% of the total glutathione pool is in the reduced form (GSH), with the remainder in the disulfide form (GSSG).[11]

In the reduced state, the thiol group of cysteinyl residue is a source of one reducing equivalent. Glutathione disulfide (GSSG) is thereby generated. The oxidized state is converted to the reduced state by NADPH.[12] This conversion is catalyzed by glutathione reductase:

NADPH + GSSG + H2O → 2 GSH + NADP+ + OH−

Roles

Antioxidant

GSH protects cells by neutralising (reducing) reactive oxygen species.[13][6] This conversion is illustrated by the reduction of peroxides:

2 GSH + R2O2 → GSSG + 2 ROH  (R = H, alkyl)

and with free radicals:

GSH + R• → 1⁄2 GSSG + RH

Regulation

Aside from deactivating radicals and reactive oxidants, glutathione participates in thiol protection and redox regulation of cellular thiol proteins under oxidative stress by protein S-glutathionylation, a redox-regulated post-translational thiol modification. The general reaction involves formation of an unsymmetrical disulfide from the protectable protein (RSH) and GSH:[14]

RSH + GSH + [O] → GSSR + H2O

Glutathione is also employed for the detoxification of methylglyoxal and formaldehyde, toxic metabolites produced under oxidative stress. This detoxification reaction is carried out by the glyoxalase system. Glyoxalase I (EC 4.4.1.5) catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-lactoylglutathione. Glyoxalase II (EC 3.1.2.6) catalyzes the hydrolysis of S-D-lactoylglutathione to glutathione and D-lactic acid.

It maintains exogenous antioxidants such as vitamins C and E in their reduced (active) states.[15][16][17]

Metabolism

Among the many metabolic processes in which it participates, glutathione is required for the biosynthesis of leukotrienes and prostaglandins. It plays a role in the storage of cysteine. Glutathione enhances the function of citrulline as part of the nitric oxide cycle.[18] It is a cofactor and acts on glutathione peroxidase.[19]

Conjugation

Glutathione facilitates metabolism of xenobiotics. Glutathione S-transferase enzymes catalyze its conjugation to lipophilic xenobiotics, facilitating their excretion or further metabolism.[20] The conjugation process is illustrated by the metabolism of N-acetyl-p-benzoquinone imine (NAPQI). NAPQI is a reactive metabolite formed by the action of cytochrome P450 on paracetamol (acetaminophen). Glutathione conjugates to NAPQI, and the resulting ensemble is excreted.

Potential neurotransmitters

Glutathione, along with oxidized glutathione (GSSG) and S-nitrosoglutathione (GSNO), bind to the glutamate recognition site of the NMDA and AMPA receptors (via their γ-glutamyl moieties). GSH and GSSG may be neuromodulators.[21][22][23] At millimolar concentrations, GSH and GSSG may also modulate the redox state of the NMDA receptor complex.[22] Glutathione binds and activates ionotropic receptors, potentially making it a neurotransmitter.[24]

GSH activates the purinergic P2X7 receptor from Müller glia, inducing acute calcium transient signals and GABA release from both retinal neurons and glial cells.[25][26]

In plants

In plants, glutathione is involved in stress management. It is a component of the glutathione-ascorbate cycle, a system that reduces poisonous hydrogen peroxide.[27] It is the precursor of phytochelatins, glutathione oligomers that chelate heavy metals such as cadmium.[28] Glutathione is required for efficient defence against plant pathogens such as Pseudomonas syringae and Phytophthora brassicae.[29] Adenylyl-sulfate reductase, an enzyme of the sulfur assimilation pathway, uses glutathione as an electron donor. Other enzymes using glutathione as a substrate are glutaredoxins. These small oxidoreductases are involved in flower development, salicylic acid, and plant defence signalling.[30]

Bioavailability

Systemic bioavailability of orally consumed glutathione is poor because the tripeptide is the substrate of proteases (peptidases) of the alimentary canal, and due to the absence of a specific carrier of glutathione at the level of cell membrane.[31][32]

Determination of glutathione

Ellman's reagent and monobromobimane

Reduced glutathione may be visualized using Ellman's reagent or bimane derivatives such as monobromobimane. The monobromobimane method is more sensitive. In this procedure, cells are lysed and thiols extracted using a HCl buffer. The thiols are then reduced with dithiothreitol and labelled by monobromobimane. Monobromobimane becomes fluorescent after binding to GSH. The thiols are then separated by HPLC and the fluorescence quantified with a fluorescence detector.

Monochlorobimane

Using monochlorobimane, the quantification is done by confocal laser scanning microscopy after application of the dye to living cells.[33] This quantification process relies on measuring the rates of fluorescence changes and is limited to plant cells.

CMFDA has also been mistakenly used as a glutathione probe. Unlike monochlorobimane, whose fluorescence increases upon reacting with glutathione, the fluorescence increase of CMFDA is due to the hydrolysis of the acetate groups inside cells. Although CMFDA may react with glutathione in cells, the fluorescence increase does not reflect the reaction. Therefore, studies using CMFDA as a glutathione probe should be revisited and reinterpreted.[34][35]

ThiolQuant Green

The major limitation of these bimane-based probes and many other reported probes is that these probes are based on irreversible chemical reactions with glutathione, which renders these probes incapable of monitoring the real-time glutathione dynamics. Recently, the first reversible reaction based fluorescent probe-ThiolQuant Green (TQG)-for glutathione was reported.[36] ThiolQuant Green can not only perform high resolution measurements of glutathione levels in single cells using a confocal microscope, but also be applied in flow cytometry to perform bulk measurements.

RealThiol

The RealThiol (RT) probe is a second-generation reversible reaction-based GSH probe. A few key features of RealThiol:

  • it has a much faster forward and backward reaction kinetics compared to ThiolQuant Green, which enables real-time monitoring of GSH dynamics in live cells;
  • only micromolar to sub-micromolar RealThiol is needed for staining in cell-based experiments, which induces minimal perturbation to GSH level in cells;
  • a high-quantum-yield coumarin fluorophore was implemented so that background noise can be minimized; and
  • equilibrium constant of the reaction between RealThiol and GSH has been fine-tuned to respond to physiologically relevant concentration of GSH.[37]

RealThiol can be used to perform measurements of glutathione levels in single cells using a high-resolution confocal microscope, as well as be applied in flow cytometry to perform bulk measurements in high throughput manner.

Organelle-targeted RT probe has also been developed. A mitochondria targeted version, MitoRT, was reported and demonstrated in monitoring the dynamic of mitochondrial glutathione both on confocoal microscope and FACS based analysis.[38]

Protein-based glutathione probes

Another approach, which allows measurement of the glutathione redox potential at a high spatial and temporal resolution in living cells, is based on redox imaging using the redox-sensitive green fluorescent protein (roGFP)[39] or redox-sensitive yellow fluorescent protein (rxYFP).[40] Because of its very low physiological concentration, GSSG is difficult to measure accurately. GSSG concentration ranges from 10 to 50 μM in all solid tissues, and from 2 to 5 μM in blood (13–33 nmol/g Hb). GSH-to-GSSG ratio of whole cell extracts is estimated from 100 to 700.[41] Those ratios represent a mixture from the glutathione pools of different redox states from different subcellular compartments (e.g. more oxidized in the ER, more reduced in the mitochondrial matrix), however. In vivo GSH-to-GSSG ratios can be measured with subcellular accuracy using fluorescent protein-based redox sensors, which have revealed ratios from 50,000 to 500,000 in the cytosol, which implies that GSSG concentration is maintained in the pM range.[42]

Uses

Winemaking

The content of glutathione in must, the first raw form of wine, determines the browning, or caramelizing effect, during the production of white wine by trapping the caffeoyltartaric acid quinones generated by enzymic oxidation as grape reaction product.[43] Its concentration in wine can be determined by UPLC-MRM mass spectrometry.[44]

See also
  • Reductive stress
  • Glutathione synthetase deficiency
  • Ophthalmic acid
  • roGFP, a tool to measure the cellular glutathione redox potential
  • Glutathione-ascorbate cycle
  • Bacterial glutathione transferase
  • Thioredoxin, a cysteine-containing small proteins with very similar functions as reducing agents
  • Glutaredoxin, an antioxidant protein that uses reduced glutathione as a cofactor and is reduced nonenzymatically by it
  • Bacillithiol
  • Mycothiol
  • γ-L-Glutamyl-L-cysteine

References
  1. Haynes, William M., ed. (2016). CRC Handbook of Chemistry and Physics (97th ed.). CRC Press. p. 3.284. ISBN 9781498754293.
  2. Pompella A, Visvikis A, Paolicchi A, De Tata V, Casini AF (October 2003). "The changing faces of glutathione, a cellular protagonist". Biochemical Pharmacology. 66 (8): 1499–1503. doi:10.1016/S0006-2952(03)00504-5. PMID 14555227.
  3. White CC, Viernes H, Krejsa CM, Botta D, Kavanagh TJ (July 2003). "Fluorescence-based microtiter plate assay for glutamate-cysteine ligase activity". Analytical Biochemistry. 318 (2): 175–180. doi:10.1016/S0003-2697(03)00143-X. PMID 12814619.
  4. Chen Y, Yang Y, Miller ML, Shen D, Shertzer HG, Stringer KF, Wang B, Schneider SN, Nebert DW, Dalton TP (May 2007). "Hepatocyte-specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failure". Hepatology. 45 (5): 1118–1128. doi:10.1002/hep.21635. PMID 17464988. S2CID 25000753.
  5. Sies H (1999). "Glutathione and its role in cellular functions". Free Radical Biology & Medicine. 27 (9–10): 916–921. doi:10.1016/S0891-5849(99)00177-X. PMID 10569624.
  6. Guoyao Wu; Yun-Zhong Fang; Sheng Yang; Joanne R. Lupton; Nancy D. Turner (2004). "Glutathione Metabolism and its Implications for Health". Journal of Nutrition. 134 (3): 489–492. doi:10.1093/jn/134.3.489. PMID 14988435.
  7. Copley SD, Dhillon JK (29 April 2002). "Lateral gene transfer and parallel evolution in the history of glutathione biosynthesis genes". Genome Biology. 3 (5): research0025. doi:10.1186/gb-2002-3-5-research0025. PMC 115227. PMID 12049666.
  8. Wonisch W, Schaur RJ (2001). "Chapter 2: Chemistry of Glutathione". In Grill D, Tausz T, De Kok L (eds.). Significance of glutathione in plant adaptation to the environment. Springer. ISBN 978-1-4020-0178-9 – via Google Books.
  9. Pastore A, Piemonte F, Locatelli M, Lo Russo A, Gaeta LM, Tozzi G, Federici G (August 2001). "Determination of blood total, reduced, and oxidized glutathione in pediatric subjects". Clinical Chemistry. 47 (8): 1467–1469. doi:10.1093/clinchem/47.8.1467. PMID 11468240.
  10. Lu SC (May 2013). "Glutathione synthesis". Biochimica et Biophysica Acta (BBA) – General Subjects. 1830 (5): 3143–3153. doi:10.1016/j.bbagen.2012.09.008. PMC 3549305. PMID 22995213.
  11. Halprin KM, Ohkawara A (1967). "The measurement of glutathione in human epidermis using glutathione reductase". The Journal of Investigative Dermatology. 48 (2): 149–152. doi:10.1038/jid.1967.24. PMID 6020678.
  12. Couto N, Malys N, Gaskell SJ, Barber J (June 2013). "Partition and turnover of glutathione reductase from Saccharomyces cerevisiae: a proteomic approach". Journal of Proteome Research. 12 (6): 2885–2894. doi:10.1021/pr4001948. PMID 23631642.
  13. Michael Brownlee (2005). "The pathobiology of diabetic complications: A unifying mechanism". Diabetes. 54 (6): 1615–1625. doi:10.2337/diabetes.54.6.1615. PMID 15919781.
  14. Dalle-Donne, Isabella; Rossi, Ranieri; Colombo, Graziano; Giustarini, Daniela; Milzani, Aldo (2009). "Protein S-glutathionylation: a regulatory device from bacteria to humans". Trends in Biochemical Sciences. 34 (2): 85–96. doi:10.1016/j.tibs.2008.11.002. PMID 19135374.
  15. Dringen R (December 2000). "Metabolism and functions of glutathione in brain". Progress in Neurobiology. 62 (6): 649–671. doi:10.1016/s0301-0082(99)00060-x. PMID 10880854. S2CID 452394.
  16. Scholz RW, Graham KS, Gumpricht E, Reddy CC (1989). "Mechanism of interaction of vitamin E and glutathione in the protection against membrane lipid peroxidation". Annals of the New York Academy of Sciences. 570 (1): 514–517. Bibcode:1989NYASA.570..514S. doi:10.1111/j.1749-6632.1989.tb14973.x. S2CID 85414084.
  17. Hughes RE (1964). "Reduction of dehydroascorbic acid by animal tissues". Nature. 203 (4949): 1068–1069. Bibcode:1964Natur.203.1068H. doi:10.1038/2031068a0. PMID 14223080. S2CID 4273230.
  18. Ha SB, Smith AP, Howden R, Dietrich WM, Bugg S, O'Connell MJ, Goldsbrough PB, Cobbett CS (June 1999). "Phytochelatin synthase genes from Arabidopsis and the yeast Schizosaccharomyces pombe". The Plant Cell. 11 (6): 1153–1164. doi:10.1105/tpc.11.6.1153. JSTOR 3870806. PMC 144235. PMID 10368185.
  19. Grant CM (2001). "Role of the glutathione/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions". Molecular Microbiology. 39 (3): 533–541. doi:10.1046/j.1365-2958.2001.02283.x. PMID 11169096. S2CID 6467802.
  20. Hayes, John D.; Flanagan, Jack U.; Jowsey, Ian R. (2005). "Glutathione transferases". Annual Review of Pharmacology and Toxicology. 45: 51–88. doi:10.1146/annurev.pharmtox.45.120403.095857. PMID 15822171.
  21. Steullet P, Neijt HC, Cuénod M, Do KQ (February 2006). "Synaptic plasticity impairment and hypofunction of NMDA receptors induced by glutathione deficit: relevance to schizophrenia". Neuroscience. 137 (3): 807–819. doi:10.1016/j.neuroscience.2005.10.014. PMID 16330153. S2CID 1417873.
  22. Varga V, Jenei Z, Janáky R, Saransaari P, Oja SS (September 1997). "Glutathione is an endogenous ligand of rat brain N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors". Neurochemical Research. 22 (9): 1165–1171. doi:10.1023/A:1027377605054. PMID 9251108. S2CID 24024090.
  23. Janáky R, Ogita K, Pasqualotto BA, Bains JS, Oja SS, Yoneda Y, Shaw CA (September 1999). "Glutathione and signal transduction in the mammalian CNS". Journal of Neurochemistry. 73 (3): 889–902. doi:10.1046/j.1471-4159.1999.0730889.x. PMID 10461878.
  24. Oja SS, Janáky R, Varga V, Saransaari P (2000). "Modulation of glutamate receptor functions by glutathione". Neurochemistry International. 37 (2–3): 299–306. doi:10.1016/S0197-0186(00)00031-0. PMID 10812215. S2CID 44380765.
  25. Freitas HR, Ferraz G, Ferreira GC, Ribeiro-Resende VT, Chiarini LB, do Nascimento JL, Matos Oliveira KR, Pereira Tde L, Ferreira LG, Kubrusly RC, Faria RX, Herculano AM, Reis RA (14 April 2016). "Glutathione-Induced Calcium Shifts in Chick Retinal Glial Cells". PLOS ONE. 11 (4): e0153677. Bibcode:2016PLoSO..1153677F. doi:10.1371/journal.pone.0153677. PMC 4831842. PMID 27078878.
  26. Freitas HR, Reis RA (1 January 2017). "Glutathione induces GABA release through P2X7R activation on Müller glia". Neurogenesis. 4 (1): e1283188. doi:10.1080/23262133.2017.1283188. PMC 5305167. PMID 28229088.
  27. Noctor G, Foyer CH (June 1998). "Ascorbate and Glutathione: Keeping Active Oxygen Under Control". Annual Review of Plant Physiology and Plant Molecular Biology. 49 (1): 249–279. doi:10.1146/annurev.arplant.49.1.249. PMID 15012235.
  28. Ha SB, Smith AP, Howden R, Dietrich WM, Bugg S, O'Connell MJ, Goldsbrough PB, Cobbett CS (June 1999). "Phytochelatin synthase genes from Arabidopsis and the yeast Schizosaccharomyces pombe". The Plant Cell. 11 (6): 1153–1164. doi:10.1105/tpc.11.6.1153. PMC 144235. PMID 10368185.
  29. Parisy V, Poinssot B, Owsianowski L, Buchala A, Glazebrook J, Mauch F (January 2007). "Identification of PAD2 as a gamma-glutamylcysteine synthetase highlights the importance of glutathione in disease resistance of Arabidopsis" (PDF). The Plant Journal. 49 (1): 159–172. doi:10.1111/j.1365-313X.2006.02938.x. PMID 17144898.
  30. Rouhier N, Lemaire SD, Jacquot JP (2008). "The role of glutathione in photosynthetic organisms: emerging functions for glutaredoxins and glutathionylation". Annual Review of Plant Biology. 59 (1): 143–166. doi:10.1146/annurev.arplant.59.032607.092811. PMID 18444899.
  31. Witschi A, Reddy S, Stofer B, Lauterburg BH (1992). "The systemic availability of oral glutathione". European Journal of Clinical Pharmacology. 43 (6): 667–669. doi:10.1007/bf02284971. PMID 1362956. S2CID 27606314.
  32. "Acetylcysteine Monograph for Professionals". Drugs.com.
  33. Meyer AJ, May MJ, Fricker M (July 2001). "Quantitative 'in vivo measurement of glutathione in Arabidopsis cells". The Plant Journal. 27 (1): 67–78. doi:10.1046/j.1365-313x.2001.01071.x. PMID 11489184. S2CID 21015139.
  34. Sebastià J, Cristòfol R, Martín M, Rodríguez-Farré E, Sanfeliu C (January 2003). "Evaluation of fluorescent dyes for measuring intracellular glutathione content in primary cultures of human neurons and neuroblastoma SH-SY5Y". Cytometry Part A. 51 (1): 16–25. doi:10.1002/cyto.a.10003. PMID 12500301. S2CID 24681280.
  35. Lantz RC, Lemus R, Lange RW, Karol MH (April 2001). "Rapid reduction of intracellular glutathione in human bronchial epithelial cells exposed to occupational levels of toluene diisocyanate". Toxicological Sciences. 60 (2): 348–355. doi:10.1093/toxsci/60.2.348. PMID 11248147.
  36. Jiang X, Yu Y, Chen J, Zhao M, Chen H, Song X, Matzuk AJ, Carroll SL, Tan X, Sizovs A, Cheng N, Wang MC, Wang J (March 2015). "Quantitative imaging of glutathione in live cells using a reversible reaction-based ratiometric fluorescent probe". ACS Chemical Biology. 10 (3): 864–874. doi:10.1021/cb500986w. PMC 4371605. PMID 25531746.
  37. Jiang X, Chen J, Bajić A, Zhang C, Song X, Carroll SL, Cai ZL, Tang M, Xue M, Cheng N, Schaaf CP, Li F, MacKenzie KR, Ferreon AC, Xia F, Wang MC, Maletić-Savatić M, Wang J (July 2017). "Quantitative imaging of glutathione". Nature Communications. 8: 16087. doi:10.1038/ncomms16087. PMC 5511354. PMID 28703127.
  38. Chen J, Jiang X, Zhang C, MacKenzie KR, Stossi F, Palzkill T, Wang MC, Wang J (2017). "Reversible Reaction-Based Fluorescent Probe for Real-Time Imaging of Glutathione Dynamics in Mitochondria". ACS Sensors. 2 (9): 1257–1261. doi:10.1021/acssensors.7b00425. PMC 5771714. PMID 28809477.
  39. Meyer AJ, Brach T, Marty L, Kreye S, Rouhier N, Jacquot JP, Hell R (December 2007). "Redox-sensitive GFP in Arabidopsis thaliana is a quantitative biosensor for the redox potential of the cellular glutathione redox buffer". The Plant Journal. 52 (5): 973–986. doi:10.1111/j.1365-313X.2007.03280.x. PMID 17892447.
  40. Maulucci G, Labate V, Mele M, Panieri E, Arcovito G, Galeotti T, Østergaard H, Winther JR, De Spirito M, Pani G (October 2008). "High-resolution imaging of redox signaling in live cells through an oxidation-sensitive yellow fluorescent protein". Science Signaling. 1 (43): pl3. doi:10.1126/scisignal.143pl3. PMID 18957692. S2CID 206670068.
  41. Giustarini D, Dalle-Donne I, Milzani A, Fanti P, Rossi R (September 2013). "Analysis of GSH and GSSG after derivatization with N-ethylmaleimide". Nature Protocols. 8 (9): 1660–1669. doi:10.1038/nprot.2013.095. PMID 23928499. S2CID 22645510.
  42. Schwarzländer M, Dick T, Meyer AJ, Morgan B (April 2016). "Dissecting Redox Biology Using Fluorescent Protein Sensors". Antioxidants & Redox Signaling. 24 (13): 680–712. doi:10.1089/ars.2015.6266. PMID 25867539.
  43. Rigaud J, Cheynier V, Souquet JM, Moutounet M (1991). "Influence of must composition on phenolic oxidation kinetics". Journal of the Science of Food and Agriculture. 57 (1): 55–63. doi:10.1002/jsfa.2740570107.
  44. Vallverdú-Queralt A, Verbaere A, Meudec E, Cheynier V, Sommerer N (January 2015). "Straightforward method to quantify GSH, GSSG, GRP, and hydroxycinnamic acids in wines by UPLC-MRM-MS". Journal of Agricultural and Food Chemistry. 63 (1): 142–149. doi:10.1021/jf504383g. PMID 25457918.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.