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• • Molecular Structure
  • Sum Formula
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  • InChIKey
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• Roles as Enzyme Ligand
• • In Vivo Substrate
  • In Vivo Product
  • Substrate
  • Product
  • Cofactor
  • Activator
  • Inhibitor
  • Metals and Ions
  • 3D Structure (PDB)
• Enzyme Kinetic Parameters
• • k_cat Value (Turnover Number)
  • K_M Value
  • K_i Value
  • IC₅₀ Value
• References & Links
• • References
  • Links

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Ligand 1,8-cineole

Basic Ligand Information

Molecular Structure

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Roles as Enzyme Ligand

In Vivo Substrate in Enzyme-catalyzed Reactions (2 results)

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Show Natural Substrate (2 entries)

EC NUMBER

PROVEN IN VIVO REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

1.14.13.156

1,8-cineole + NADPH + H+ + O2 = 2-endo-hydroxy-1,8-cineole + NADP+ + H2O

744316, 746358

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1.14.14.133

1,8-cineole + [reduced NADPH-hemoprotein reductase] + O2 = 2-endo-hydroxy-1,8-cineole + [oxidized NADPH-hemoprotein reductase] + H2O

744316, 746360

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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

4.2.3.108

geranyl diphosphate + H2O = 1,8-cineole + diphosphate

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Substrate in Enzyme-catalyzed Reactions (8 results)

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Show Substrate (8 entries)

EC NUMBER

REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

1.14.13.156

1,8-cineole + NADPH + H+ + O2 = 2-endo-hydroxy-1,8-cineole + NADP+ + H2O

744316, 746358

-

1.14.14.108

1,3,3-trimethyl-2-oxabicyclo-(2,2,2)octane + NADH + O2 = 1,6,6-trimethyl-2,7-dioxa(3,2,2)bicyclononan-3-one + NAD+ + H2O

286367

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1.14.14.133

1,8-cineole + [reduced flavodoxin] + O2 = (1R)-6beta-hydroxycineole + [oxidized flavodoxin] + H2O

717774, 717156, 717765

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1.14.14.133

1,8-cineole + [reduced flavodoxin] + O2 = 6beta-hydroxycineole + [oxidized flavodoxin] + H2O

717775

-

1.14.14.133

1,8-cineole + [reduced NADPH-hemoprotein reductase] + O2 = 2-endo-hydroxy-1,8-cineole + [oxidized NADPH-hemoprotein reductase] + H2O

744316, 746360

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1.14.14.56

1,8-cineole + [reduced NADPH-hemoprotein reductase] + H+ + O2 = 2-exo-hydroxy-1,8-cineole + [oxidized NADPH-hemoprotein reductase] + H2O

718453, 717531

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1.14.14.56

1,8-cineole + [reduced NADPH-hemoprotein reductase] + H+ + O2 = 2alpha-hydroxy-1,8-cineole + [oxidized NADPH-hemoprotein reductase] + H2O

717270

-

1.14.14.56

1,8-cineole + [reduced NADPH-hemoprotein reductase] + H+ + O2 = 3alpha-hydroxy-1,8-cineole + [oxidized NADPH-hemoprotein reductase] + H2O

717270

-

1.14.14.133

3 entries

1.14.14.56

3 entries

Product in Enzyme-catalyzed Reactions (3 results)

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Show Product (3 entries)

EC NUMBER

REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

4.2.3.108

geranyl diphosphate + H2O = 1,8-cineole + diphosphate

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4.2.3.108

geranyl diphosphate = 1,8-cineole + diphosphate

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-

4.2.3.108

neryl diphosphate + H2O = 1,8-cineole + diphosphate

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-

4.2.3.108

3 entries

Inhibitor in Enzyme-catalyzed Reactions (4 results)

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Show Inhibitors (4 entries)

EC NUMBER

COMMENTARY

LITERATURE

ENZYME 3D STRUCTURE

3.1.1.7

isolated from Melaleuca atlernifolia

691944

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3.1.1.7

IC50 is 0.015 mg/ml

708829

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3.1.1.8

isolated from Melaleuca atlernifolia

691944

-

3.1.1.8

48.2% inhibition at 1 mM

695287

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3.1.1.7

2 entries

3.1.1.8

2 entries

Enzyme Kinetic Parameters

K_M Value (6 results)

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Show KM Value (6 entries)

EC NUMBER

KM VALUE [MM]

KM VALUE MAXIMUM [MM]

COMMENTARY

LITERATURE

1.14.14.56

0.012

-

pH 7.4, 37°C, formation of 2-hydroxy-1,8-cineole by isoform CYP3A4

717270

1.14.14.56

0.019

-

pH 7.4, 37°C, formation of 3-hydroxy-1,8-cineole by isoform CYP3A4

717270

1.14.14.56

0.02

-

pH 7.4, 37°C, after treatment of animals with pregenolone-16alpha-carbonitrile

717531

1.14.14.56

0.05

-

pH 7.4, 37°C

717531

1.14.14.56

0.141

-

pH 7.4, 37°C, formation of 3-hydroxy-1,8-cineole by isoform CYP3A5

717270

1.14.14.56

0.599

-

pH 7.4, 37°C, formation of 2-hydroxy-1,8-cineole by isoform CYP3A5

717270

1.14.14.56

6 entries

References & Links

Literature References (14)

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Show Reference (14 entries)

BRENDA REFERENCE ID

PUBMED ID

TITLE

YEAR

AUTHORS

JOURNAL

VOLUME

PAGES

286367

-

Metabolism of 1,8-cineole by a Rhodococcus species: Ring cleavage reactions

1989

Williams, D.R.; Trudgill, P.W.; Taylor, D.G.

J. Gen. Microbiol.

135

1957-1967

691944

18473814

Natural products and their derivatives as cholinesterase inhibitors in the treatment of neurodegenerative disorders: an update

2008

Loizzo, M.R.; Tundis, R.; Menichini, F.; Menichini, F.

Curr. Med. Chem.

15

1209-1228

695287

18810999

Activity of essential oils and individual components against acetyl- and butyrylcholinesterase

2008

Orhan, I.; Kartal, M.; Kan, Y.; Sener, B.

Z. Naturforsch. C

63

547-553

708829

19358605

Acetylcholinesterase inhibitory activity and chemical composition of commercial essential oils

2009

Dohi, S.; Terasaki, M.; Makino, M.

J. Agric. Food Chem.

57

4313-4318

717156

20851096

Oxygen activation by P450(cin): Protein and substrate mutagenesis

2011

Slessor, K.E.; Farlow, A.J.; Cavaignac, S.M.; Stok, J.E.; De Voss, J.J.

Arch. Biochem. Biophys.

507

154-162

717270

15715982

Metabolism of 1,8-cineole by human cytochrome P450 enzymes: identification of a new hydroxylated metabolite

2005

Duisken, M.; Sandner, F.; Bloemeke, B.; Hollender, J.

Biochim. Biophys. Acta

1722

304-311

717531

11159812

Oxidation of 1,8-cineole, the monoterpene cyclic ether originated from Eucalyptus polybractea, by cytochrome P450 3A enzymes in rat and human liver microsomes

2001

Miyazawa, M.; Shindo, M.; Shimada, T.

Drug Metab. Dispos.

29

200-205

717765

12016226

Cytochrome P450(cin) (CYP176A), isolation, expression, and characterization

2002

Hawkes, D.B.; Adams, G.W.; Burlingame, A.L.; Ortiz de Montellano, P.R.; De Voss, J.J.

J. Biol. Chem.

277

27725-27732

717774

17606612

Electron transfer between cytochrome P450cin and its FMN-containing redox partner, cindoxin

2007

Kimmich, N.; Das, A.; Sevrioukova, I.; Meharenna, Y.; Sligar, S.G.; Poulos, T.L.

J. Biol. Chem.

282

27006-27011

717775

18270198

The critical role of substrate-protein hydrogen bonding in the control of regioselective hydroxylation in p450cin

2008

Meharenna, Y.T.; Slessor, K.E.; Cavaignac, S.M.; Poulos, T.L.; De Voss, J.J.

J. Biol. Chem.

283

10804-10812

718453

11695850

Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes

2001

Miyazawa, M.; Shindo, M.; Shimada, T.

Xenobiotica

31

713-723

744316

24533927

Crystal structure of cindoxin, the P450cin redox partner

2014

Madrona, Y.; Hollingsworth, S.; Tripathi, S.; Fields, J.; Rwigema, J.; Tobias, D.; Poulos, T.

Biochemistry

53

1435-1446

746358

28007937

Directed evolution of P450cin for mediated electron transfer

2017

Belsare, K.; Horn, T.; Ruff, A.; Martinez, R.; Magnusson, A.; Holtmann, D.; Schrader, J.; Schwaneberg, U.

Protein Eng.

Des. Sel.

119-127

746360

28007937

Directed evolution of P450cin for mediated electron transfer

2017

Belsare, K.; Horn, T.; Ruff, A.; Martinez, R.; Magnusson, A.; Holtmann, D.; Schrader, J.; Schwaneberg, U.

Protein Eng. Des. Sel.

30

119-127

Links to other databases for 1,8-cineole

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Show Links (1 entry)

ChEBI

PubChem

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