KEAP1-NFE2L2 pathway

Hayes JD, Dinkova-Kostova AT, Tew KD. Oxidative Stress in Cancer. Cancer Cell. 2020 Aug 10;38(2):167–97. PMID: 32649885; PMCID: PMC7439808.; He F, Ru X, Wen T. NRF2, a Transcription Factor for Stress Response and Beyond. Int J Mol Sci. 2020 Jul 06;21(13). PMID: 32640524; PMCID: PMC7369905.; Baird L, Yamamoto M. The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway. Molecular and Cellular Biology. 2020 Jun 15;40(13). doi: 10.1128/mcb.00099-20.; Ge T, Yang J, Zhou S, Wang Y, Li Y, Tong X. The Role of the Pentose Phosphate Pathway in Diabetes and Cancer. Front Endocrinol (Lausanne). 2020;11():365. PMID: 32582032; PMCID: PMC7296058.; Cuadrado A, Rojo AI, Wells G, Hayes JD, Cousin SP, Rumsey WL, Attucks OC, Franklin S, Levonen AL, Kensler TW, Dinkova-Kostova AT. Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat Rev Drug Discov. 2019 Apr;18(4):295–317. doi: 10.1038/s41573-018-0008-x. PMID: 30610225.; Cuadrado A, Manda G, Hassan A, Alcaraz MJ, Barbas C, Daiber A, Ghezzi P, León R, López MG, Oliva B, Pajares M, Rojo AI, Robledinos-Antón N, Valverde AM, Guney E, Schmidt HHHW. Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach. Pharmacol Rev. 2018 Apr;70(2):348–83. doi: 10.1124/pr.117.014753. PMID: 29507103.; Kitamura H, Motohashi H. NRF2 addiction in cancer cells. Cancer Sci. 2018 Apr;109(4):900–11. PMID: 29450944; PMCID: PMC5891176.

Metabolites

H+

Formula: H (1.0078246)

CAS ID: 12408-02-5

H2O

Formula: H2O (18.0105642)

CAS ID: 7732-18-5

Hydrogen peroxide

Formula: H2O2 (34.0054792)

CAS ID: 7722-84-1

Magnesium cation

Formula: Mg (23.98505)

CAS ID: 22537-22-0

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

thiamine(1+) diphosphate(3-)

Formula: C12H16N4O7P2S (422.0214926)

CAS ID:

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:

NADP(3-)

Formula: C21H25N7O17P3 (740.051977)

CAS ID: 53-59-8



Enzyme

EC Number name full name note
1.-.-.-
1.1.1.42 isocitrate dehydrogenase (NADP+) isocitrate:NADP+ oxidoreductase (decarboxylating)
1.1.1.44 phosphogluconate dehydrogenase (NADP+-dependent, decarboxylating) 6-phospho-D-gluconate:NADP+ 2-oxidoreductase (decarboxylating)
1.1.1.49 glucose-6-phosphate dehydrogenase (NADP+) D-glucose-6-phosphate:NADP+ 1-oxidoreductase
1.11.1.2 NADPH peroxidase NADPH:hydrogen-peroxide oxidoreductase
1.11.1.24 thioredoxin-dependent peroxiredoxin thioredoxin:hydroperoxide oxidoreductase
1.14.14.18 heme oxygenase (biliverdin-producing) protoheme,NADPH-hemoprotein reductase:oxygen oxidoreductase (alpha-methene-oxidizing, hydroxylating)
1.15.1.1 superoxide dismutase superoxide:superoxide oxidoreductase
1.6.5.2 NAD(P)H dehydrogenase (quinone) NAD(P)H:quinone oxidoreductase
1.8.1.9 thioredoxin-disulfide reductase thioredoxin:NADP+ oxidoreductase
1.8.98.2 sulfiredoxin peroxiredoxin-(S-hydroxy-S-oxocysteine):thiol oxidoreductase [ATP-hydrolysing; peroxiredoxin-(S-hydroxycysteine)-forming]
2.2.1.1 transketolase sedoheptulose-7-phosphate:D-glyceraldehyde-3-phosphate glycolaldehydetransferase
2.2.1.2 transaldolase sedoheptulose-7-phosphate:D-glyceraldehyde-3-phosphate glyceronetransferase
2.3.2.27 RING-type E3 ubiquitin transferase [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (isopeptide bond-forming; RING-type)
2.3.2.32 cullin-RING-type E3 NEDD8 transferase [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine:[cullin] [NEDD8-protein] transferase (isopeptide bond-forming; RING-type)
2.5.1.18 glutathione transferase RX:glutathione R-transferase
2.7.10.2 non-specific protein-tyrosine kinase ATP:[protein]-L-tyrosine O-phosphotransferase (non-specific)
2.7.11.1 non-specific serine/threonine protein kinase ATP:protein phosphotransferase (non-specific)
2.7.11.13 protein kinase C ATP:protein phosphotransferase (diacylglycerol-dependent)
2.7.11.26 tau-protein kinase ATP:[tau-protein] O-phosphotransferase
2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase ATP:[hydroxymethylglutaryl-CoA reductase (NADPH)] phosphotransferase
3.4.14.4 dipeptidyl-peptidase III
3.6.4.6 vesicle-fusing ATPase ATP phosphohydrolase (vesicle-fusing)
6.3.2.2 glutamate-cysteine ligase L-glutamate:L-cysteine gamma-ligase (ADP-forming)
7.6.2.2 ABC-type xenobiotic transporter ATP phosphohydrolase (ABC-type, xenobiotic-exporting)
7.6.2.3 ABC-type glutathione-S-conjugate transporter ATP + H2O + glutathione-S-conjugate[side 1] = ADP + phosphate + glutathione-S-conjugate[side 2]


Proteins

Protein ID name full name