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Ligand leucovorin

Basic Ligand Information

Molecular Structure

Related pathways

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Roles as Enzyme Ligand

In Vivo Substrate in Enzyme-catalyzed Reactions (1 result)

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Show Natural Substrate (1 entry)

EC NUMBER

PROVEN IN VIVO REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

7.6.2.2

ATP + H2O + leucovorin/in = ADP + phosphate + leucovorin/out

701356

-

In Vivo Product in Enzyme-catalyzed Reactions (1 result)

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Show Natural Product (1 entry)

EC NUMBER

PROVEN IN VIVO REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

7.6.2.2

ATP + H2O + leucovorin/in = ADP + phosphate + leucovorin/out

-

-

Substrate in Enzyme-catalyzed Reactions (5 results)

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Show Substrate (5 entries)

EC NUMBER

REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

3.5.2.13

formyltetrahydrofolate + H2O = methylenetetrahydrofolate + ?

688323

-

6.3.3.2

ATP + (6R,S)-5-formyltetrahydrofolate = ADP + phosphate + 5,10-methenyltetrahydrofolate

1319

-

6.3.3.2

ATP + (6R,S)-5-formyltetrahydropteroyl-Glu = ?

1330, 1329

-

7.6.2.2

ATP + H2O + leucovorin/in = ADP + phosphate + leucovorin/out

701356

-

7.6.2.2

ATP + H2O + leucovorin[side 1] = ADP + phosphate + leucovorin[side 2]

747619

-

6.3.3.2

2 entries

7.6.2.2

2 entries

Product in Enzyme-catalyzed Reactions (2 results)

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Show Product (2 entries)

EC NUMBER

REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

7.6.2.2

ATP + H2O + leucovorin/in = ADP + phosphate + leucovorin/out

-

-

7.6.2.2

ATP + H2O + leucovorin[side 1] = ADP + phosphate + leucovorin[side 2]

-

-

7.6.2.2

2 entries

Activator in Enzyme-catalyzed Reactions (1 result)

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Show Activating Compound (1 entry)

EC NUMBER

COMMENTARY

LITERATURE

ENZYME 3D STRUCTURE

1.3.1.1

-

686495

-

Inhibitor in Enzyme-catalyzed Reactions (3 results)

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Show Inhibitors (3 entries)

EC NUMBER

COMMENTARY

LITERATURE

ENZYME 3D STRUCTURE

2.1.2.1

leucovorin (N5-CHO-THF) exhibits a differential inhibition pattern: it significantly inhibits the aldol cleavage of serine catalyzed by zebrafish cytosolic SHMT but it inhibits to a lesser extent the reaction catalyzed by the mitochondrial isozyme. Approximately 70% and 30% inhibition are observed for zebrafish cytosolic- and zebrafish mitochondrial SHMT activities, respectively, in the presence of 70 mM leucovorin. An even larger difference between both isoenzymes is observed when the inhibition is assayed in the presence of 50 mM serine; leucovorin (N5-CHO-THF) exhibits a differential inhibition pattern: it significantly inhibits the aldol cleavage of serine catalyzed by zebrafish cytosolic SHMT but it inhibits to a lesser extent the reaction catalyzed by the mitochondrial isozyme. Approximately 70% and 30% inhibition are observed for zebrafish cytosolic- and zebrafish mitochondrial SHMT activities, respectively, in the presence of 70 mM leucovorin. An even larger difference between both isoenzymes is observed when the inhibition is assayed in the presence of 50 mM serine

686353

-

2.1.2.13

-

757485

-

6.3.4.3

-

1506

-

Enzyme Kinetic Parameters

K_M Value (4 results)

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Show KM Value (4 entries)

EC NUMBER

KM VALUE [MM]

KM VALUE MAXIMUM [MM]

COMMENTARY

LITERATURE

6.3.3.2

0.004

-

-

1319

6.3.3.2

0.0044

-

cytosolic enzyme

1329

6.3.3.2

0.0047

-

-

1330

6.3.3.2

0.0047

-

mitochondrial enzyme

1329

6.3.3.2

4 entries

IC₅₀ Value (2 results)

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Show IC50 Value (2 entries)

EC NUMBER

IC50 VALUE

IC50 VALUE MAXIMUM

COMMENTARY

LITERATURE

2.1.2.1

30

-

-

686353

2.1.2.1

70

-

-

686353

2.1.2.1

2 entries

References & Links

Literature References (10)

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Show Reference (10 entries)

BRENDA REFERENCE ID

PUBMED ID

TITLE

YEAR

AUTHORS

JOURNAL

VOLUME

PAGES

1319

3801490

Human liver methenyltetrahydrofolate synthetase: improved purification and increased affinity for folate polyglutamate substrates

1987

Bertrand, R.; MacKenzie, R.E.; Jolivot, J.

Biochim. Biophys. Acta

911

154-161

1329

9250980

Human 5,10-methenyltetrahydrofolate synthetase

1997

Jolivet, J.

Methods Enzymol.

281

162-170

1330

7766710

Identification and characterization of human mitochondrial methenyltetrahydrofolate synthetase activity

1995

Bertrand, R.; Beauchemin, M.; Dayan, A.; Ouimet, M.; Jolivet, J.

Biochim. Biophys. Acta

1266

245-2549

1506

7374504

Purification and properties of formyltetrahydrofolate synthetase

1980

Buttlaire, D.H.

Methods Enzymol.

66

585-599

686353

17664250

Serine hydroxymethyltransferase isoforms are differentially inhibited by leucovorin: characterization and comparison of recombinant zebrafish serine hydroxymethyltransferases

2007

Chang, W.N.; Tsai, J.N.; Chen, B.H.; Huang, H.S.; Fu, T.F.

Drug Metab. Dispos.

35

2127-2137

686495

17097873

Increased dihydropyrimidine dehydrogenase activity associated with mild toxicity in patients treated with 5-fluorouracil and leucovorin

2007

van Kuilenburg, A.B.; Klumpen, H.; Westermann, A.M.; Zoetekouw, L.; Van Lenthe, H.; Bakker, P.J.; Richel, D.J.; Guchelaar, H.

Eur. J. Cancer

43

459-465

688323

18309272

Crystallization and preliminary X-ray diffraction analysis of 5,10-methylenetetrahydrofolate dehydrogenase/cyclohydrolase from Thermoplasma acidophilum DSM 1728

2008

Kim, J.H.; Sung, M.W.; Lee, E.H.; Nam, K.H.; Hwang, K.Y.

J. Microbiol. Biotechnol.

18

283-286

701356

18353444

Multidrug resistance protein 4 (MRP4/ABCC4): a versatile efflux transporter for drugs and signalling molecules

2008

Russel, F.G.; Koenderink, J.B.; Masereeuw, R.

Trends Pharmacol. Sci.

29

200-207

747619

29022498

ATP-binding cassette exporters structure and mechanism with a focus on P-glycoprotein and MRP1

2017

Arana, M.R.; Altenberg, G.

Curr. Med. Chem.

25

1-17

757485

-

Homology modeling and molecular docking studies of ArnA protein from Erwinia amylovora role in polymyxin antibiotic resistance

2015

Sonawane, K.; Parulekar, R.; Malkar, R.; Nimbalkar, P.; Barage, S.; Jadhav, D.

J. Plant Biochem. Biotechnol.

24

425-432

Links to other databases for leucovorin

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Show Links (1 entry)