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IntEnz - Home
IntEnz (Integrated relational Enzyme database) is a freely available resource
focused on enzyme nomenclature. IntEnz is created in collaboration with the
Swiss Institute of Bioinformatics (SIB).
This collaboration is responsible for the production of the
ENZYME resource.
IntEnz contains the recommendations of the Nomenclature Committee of the
International Union of Biochemistry and
Molecular Biology (NC-IUBMB) on the nomenclature and classification of
enzyme-catalysed reactions.
All data in IntEnz is freely accessible and available for anyone to use.
Enzyme spotlight
Abstract:
Nitrosyl,
commonly referred to as nitric oxide (NO) in the biochemical literature,
is a free radical generated in biological systems. NO functions at low
concentrations as a signal in many diverse physiological processes such
as blood pressure control, neurotransmission, learning and memory, and at high
concentrations as a defensive cytotoxin.
Nitric oxide synthase (NOS) enzymes produce NO by catalysing a five-electron
oxidation of a guanidino nitrogen of
L-arginine.
Oxidation of L-arginine to
L-citrulline
occurs via two successive monooxygenation reactions producing
Nω-hydroxy-L-arginine
as an intermediate. 2 mol of dioxygen (O 2) and 1.5 mol of NADPH are
consumed per mole of NO formed [1]:
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2 × (L-arginine + NADPH + H+ + O2 →
Nω-hydroxy-L-arginine +
H2O + NADP+)
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2 Nω-hydroxy-L-arginine +
NADPH + H+ + 2 O2 → 2
L-citrulline + 2 H2O + NADP+ + 2 NO
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2 L-arginine + 3 NADPH + 3 H+ +
4 O2 → 2 L-citrulline +
4 H2O + 3 NADP+ + 2 NO
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NOS is the only enzyme known to simultaneously require five bound cofactors:
FAD, FMN, heme, tetrahydrobiopterin and Ca 2+-calmodulin (CaM).
In mammals, three distinct genes encode NOS isozymes: neuronal (nNOS or NOS-1),
cytokine-inducible (iNOS or NOS-2) and endothelial (eNOS or NOS-3).
iNOS and nNOS are soluble and found predominantly in the cytosol, while eNOS is
membrane-associated.
The enzymes exist as homodimers, each monomer consisting of two major domains:
N-terminal oxygenase domain, which belongs to the class of heme-thiolate
proteins, and C-terminal reductase domain, which is homologous to
NADPH—P450 reductase.
Classic descriptions of enzyme activity rely on formalisms that explicitly
depend on steady-state assumptions. In contrast to metabolic enzymes
("enzymes of mass conversion"), signal-generating enzymes transfer information,
rather than material, and steady-state descriptions may not be appropriate.
Recently, it was shown that at physiological temperatures nNOS produces sharp
pulses of NO, consistent with its signalling function [2].
References:
Stuehr, D., Pou, S. and Rosen, G.M. (2001)
Oxygen reduction by nitric-oxide synthases.
Salerno, J.C. (2008)
Neuronal nitric oxide synthase: Prototype for pulsed enzymology.
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of previous releases spotlights.
Acknowledgements
The project was supported by the European Commission under FELICS,
contract number 021902 (RII3) within the Research Infrastructure Action
of the FP6 "Structuring the European Research Area" Programme.
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