Theoretical analysis of biochemical pathways of nitric oxide release from vascular endothelial cells
Catherine
Lloyd
Bioengineering Institute, University of Auckland
Model Status
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Model Structure
Nitric oxide (NO) plays an essential role in a diverse range of physiological and pathological processes, including acting as a potent vasodilator. NO can be synthesised in a reaction catalysed by the enzyme nitric oxide synthase (NOS), of which there are three isoforms: neuronal NOS (nNOS or NOS1), inducible NOS (iNOS or NOS2), and endothelial NOS (eNOS or NOS3). The substrates required for NO synthesis include: L-arginine (Arg), oxygen (O2), and nicotinamide adenine dinucleotide phosphate (NADPH). Once NO is synthesised in the vasculature, it diffuses into the smooth muscle of the blood vessel walls, resulting in muscle relaxation and vasodilation. As such, NO derived from NOS3 has been considered as the main regulator of vascular tone. However, despite its physiological importance, there is a general lack of data on NO production and how its distribution changes around arterioles under different oxygen conditions, mainly due to experimental limitations.
In the study described here in CellML, Kejing Chen and Aleksander Popel have focused on NO production catalysed by eNOS in particular, and they have developed a mathematical model to capture the characteristics of this biochemical pathway. A schematic diagram of the reactions included in this model is outlined in the figure below.
model diagram
Schematic diagram of the mathematical model. Pathway of nitric oxide (NO) synthesis catalysed by endothelial nitric oxide synthase (eNOS, or eNOS3). The heme iron (Fe) is the main catalysis site and is used to represent the enzyme in this figure and also in the model. The heme ion of eNOS binds L-arginine (Arg), hydroxyl-L-arginine (NOHA), and oxygen (O2), and undergoes a series of oxygenation and reduction reactions.
The complete original paper reference is cited below:
=Theoretical analysis of biochemical pathways of nitric oxide release from vascular endothelial cells, Kejing Chen and Aleksander S. Popel, 2006,
Free Radical Biology and Medicine
, 41, 668-680. PubMed ID: 16864000
Arg
L-arginine
Fe3
neuronal nitric oxide synthase (heme iron 3+)
Fe3_Arg
neuronal nitric oxide synthase (heme iron 3+) bound to L-arginine
Fe2
neuronal nitric oxide synthase (heme iron 2+)
Fe2_Arg
neuronal nitric oxide synthase (heme iron 2+) bound to L-arginine
Fe3_O2_Arg
oxidised neuronal nitric oxide synthase (heme iron 3+) bound to L-arginine
Fe3_NOHA
neuronal nitric oxide synthase (heme iron 3+) bound to hydroxyl-L-arginine
Fe2_NOHA
neuronal nitric oxide synthase (heme iron 2+) bound to hydroxyl-L-arginine
Fe3_O2_NOHA
oxidised neuronal nitric oxide synthase (heme iron 3+) bound to hydroxyl-L-arginine
Fe3_NO
neuronal nitric oxide synthase (heme iron 3+) bound to nitric oxide
Fe2_NO
neuronal nitric oxide synthase (heme iron 2+) bound to nitric oxide
NO
nitric oxide
NO3
nitrate
NOHA
hydroxyl-L-arginine
nitric oxide
nitric oxide synthase
signal transduction
cerebral aneurysm
Catherine Lloyd
Theoretical analysis of biochemical pathways of nitric oxide release from vascular endothelial cells
41
668
680
Free Radical Biology and Medicine
The University of Auckland, Bioengineering Institute
keyword
This is a CellML description of Chen and Popel's 2006 mathematical model of biochemical pathways of nitric oxide release from vascular endothelial cells.
The University of Auckland
The Bioengineering Institute
Catherine
Lloyd
May
2007-08-30T00:00:00+00:00
c.lloyd@auckland.ac.nz
2006-08-15
Kejing
Chen
Aleksander
Popel
S
16864000
Chen and Popel's 2006 mathematical model of biochemical pathways of nitric oxide release from vascular endothelial cells.