Citric acid cycle (TCA cycle)

Kang W, Suzuki M, Saito T, Miyado K. Emerging Role of TCA Cycle-Related Enzymes in Human Diseases. Int J Mol Sci. 2021 Dec 02;22(23). PMID: 34884868; PMCID: PMC8657694.; Zhang GF, Jensen MV, Gray SM, El K, Wang Y, Lu D, Becker TC, Campbell JE, Newgard CB. Reductive TCA cycle metabolism fuels glutamine- and glucose-stimulated insulin secretion. Cell Metab. 2021 Apr 06;33(4):804–817.e5. PMID: 33321098; PMCID: PMC8115731.; Hayashi Y, Yokota A, Harada H, Huang G. Hypoxia/pseudohypoxia-mediated activation of hypoxia-inducible factor-1a in cancer. Cancer Sci. 2019 May;110(5):1510–7. PMID: 30844107; PMCID: PMC6501028.; Jiang L, Shestov AA, Swain P, Yang C, Parker SJ, Wang QA, Terada LS, Adams ND, McCabe MT, Pietrak B, Schmidt S, Metallo CM, Dranka BP, Schwartz B, DeBerardinis RJ. Reductive carboxylation supports redox homeostasis during anchorage-independent growth. Nature. 2016 Apr 14;532(7598):255–8. PMID: 27049945; PMCID: PMC4860952.; Pollard PJ, Brière JJ, Alam NA, Barwell J, Barclay E, Wortham NC, Hunt T, Mitchell M, Olpin S, Moat SJ, Hargreaves IP, Heales SJ, Chung YL, Griffiths JR, Dalgleish A, McGrath JA, Gleeson MJ, Hodgson SV, Poulsom R, Rustin P, Tomlinson IP. Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations. Hum Mol Genet. 2005 Aug 01;14(15):2231–9. doi: 10.1093/hmg/ddi227. PMID: 15987702.; Ochoa S. The pursuit of a hobby. Annu Rev Biochem. 1980;49():1–30. doi: 10.1146/annurev.bi.49.070180.000245. PMID: 6773467.; Krebs HA, Eggleston LV. The oxidation of pyruvate in pigeon breast muscle. Biochem J. 1940 Mar;34(3):442–59. PMID: 16747180; PMCID: PMC1265297.; Krebs HA, Salvin E, Johnson WA. The formation of citric and alpha-ketoglutaric acids in the mammalian body. Biochem J. 1938 Jan;32(1):113–7. PMID: 16746585; PMCID: PMC1264001.

Metabolites

Calcium cation

Formula: Ca (39.962591)

CAS ID: 14127-61-8

CO2

Formula: CO2 (43.98983)

CAS ID: 124-38-9

Fe2+

Formula: Fe (55.934939)

CAS ID: 15438-31-0

H+

Formula: H (1.0078246)

CAS ID: 12408-02-5

H2O

Formula: H2O (18.0105642)

CAS ID: 7732-18-5

Magnesium cation

Formula: Mg (23.98505)

CAS ID: 22537-22-0

Manganese(2+)

Formula: Mn (54.938046)

CAS ID: 7439-96-5

Ubiquinone-10

Formula: C59H90O4 (862.683874)

CAS ID: 303-98-0

Ubiquinol-10

Formula: C59H92O4 (864.6995231999999)

CAS ID: 5677-55-4

oxaloacetate(2-)

Formula: C4H2O5 (129.9902242)

CAS ID: 149-63-3

2-oxoglutarate(2-)

Formula: C5H4O5 (144.00587339999998)

CAS ID: 64-15-3

succinate(2-)

Formula: C4H4O4 (116.01095839999999)

CAS ID: 56-14-4

butenedioate

Formula: C4H2O4 (113.99530920000001)

CAS ID: 17013-01-3

4-hydroxybutyrate

Formula: C4H7O3 (103.0395172)

CAS ID: 1320-61-2

citrate(3-)

Formula: C6H5O7 (189.00352800000002)

CAS ID: 126-44-3

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

NAD(1-)

Formula: C21H26N7O14P2 (662.1012936000001)

CAS ID: 53-84-9

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
1.1.1.37 malate dehydrogenase (S)-malate:NAD+ oxidoreductase
1.1.1.41 isocitrate dehydrogenase (NAD+) isocitrate:NAD+ oxidoreductase (decarboxylating)
1.16.3.1 ferroxidase Fe(II):oxygen oxidoreductase
1.3.5.1 succinate dehydrogenase succinate:quinone oxidoreductase
1.8.1.4 dihydrolipoyl dehydrogenase protein-N6-(dihydrolipoyl)lysine:NAD+ oxidoreductase
2.3.1.61 dihydrolipoyllysine-residue succinyltransferase succinyl-CoA:enzyme-N6-(dihydrolipoyl)lysine S-succinyltransferase
2.3.3.16 citrate synthase (unknown stereospecificity) acetyl-CoA:oxaloacetate C-acetyltransferase (thioester-hydrolysing)
4.2.1.2 fumarate hydratase (S)-malate hydro-lyase (fumarate-forming)
4.2.1.3 aconitate hydratase citrate(isocitrate) hydro-lyase (cis-aconitate-forming)
6.2.1.5 succinate-CoA ligase (ADP-forming) succinate:CoA ligase (ADP-forming)


Proteins

Protein ID name full name
O00087 dld1 Dihydrolipoyl dehydrogenase, mitochondrial
O13696 idh1 Isocitrate dehydrogenase [NAD] subunit 1, mitochondrial
O13750 SUCA_SCHPO Succinate--CoA ligase [ADP-forming] subunit alpha, mitochondrial
O13966 ACON_SCHPO Aconitate hydratase, mitochondrial
O74831 FRDA_SCHPO Frataxin homolog, mitochondrial
O94415 SUCB_SCHPO Succinate--CoA ligase [ADP-forming] subunit beta, mitochondrial
O94552 fum1 Fumarate hydratase, mitochondrial
O94681 kgd2 Probable dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial
P21911 sdh2 Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial
Q10306 cit1 Probable citrate synthase, mitochondrial
Q9USP8 idh2 Isocitrate dehydrogenase [NAD] subunit 2, mitochondrial
Q9UTJ7 sdh1 Probable succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
Q9Y7R8 MDH1 Malate dehydrogenase, mitochondrial