Vascular and perivascular nitric oxide release and transport: biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3)

Vascular and perivascular nitric oxide release and transport: biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3)

Model Status

This model is known to run in PCEnv and COR and is known to be mathematically consistent with the publication it was based on. This model has had an equation added to allow it to reproduce Figure 2 of the publication. The three different graphs of this figure can be produced by altering the variable 'Fe3' in the 'Fe3' component (this variable represents the concentration of NOS-1 in its Fe3+ bound state) to 0.6 or 0.9 micromolar.

ValidateCellML verifies this model as valid CellML with consistent units.

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 (NOS1), inducible NOS (NOS2), and endothelial NOS (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 produced a mathematical model to capture the characteristics of the biochemical pathway of neuronal nitric oxide synthase (NOS1). A schematic diagram of the reactions included in this model is outlined in the figure below.

Schematic diagram of the mathematical model. Pathway of NO release and transport catalysed by neuronal nitric oxide synthase ((NOS1), here represented by the heme iron (Fe)). The heme ion of NOS1 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:

Vascular and perivascular nitric oxide release and transport: biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3), Kejing Chen and Aleksander S. Popel, 2007, Free Radical Biology and Medicine , 42, 811-822. (Full text and PDF versions of the article are available to journal subscribers on the Free Radical Biology and Medicine website.) PubMed ID: 17320763