Chen2006 - Nitric Oxide Release from Endothelial Cells
This model is described in the article:
Abstract:
Vascular endothelium expressing endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO), which has a number of important physiological functions in the microvasculature. The rate of NO production by the endothelium is a critical determinant of NO distribution in the vascular wall. We have analyzed the biochemical pathways of NO synthesis and formulated a model to estimate NO production by the microvascular endothelium under physiological conditions. The model quantifies the NO produced by eNOS based on the kinetics of NO synthesis and the availability of eNOS and its intracellular substrates. The predicted NO production from microvessels was in the range of 0.005-0.1 microM/s. This range of predicted values is in agreement with some experimental values but is much lower than other rates previously measured or estimated from experimental data with the help of mathematical modeling. Paradoxical discrepancies between the model predictions and previously reported results based on experimental measurements of NO concentration in the vicinity of the arteriolar wall suggest that NO can also be released through eNOS-independent mechanisms, such as catalysis by neuronal NOS (nNOS). We also used our model to test the sensitivity of NO production to substrate availability, eNOS concentration, and potential rate-limiting factors. The results indicated that the predicted low level of NO production can be attributed primarily to a low expression of eNOS in the microvascular endothelial cells.
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Theoretical analysis of biochemical pathways of nitric oxide release from vascular endothelial cells.
- Chen K, Popel AS
- Free radical biology & medicine , 8/ 2006 , Volume 41 , Issue 4 , pages: 668-680 , PubMed ID: 16864000
- Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, 720 Rutland Avenue, 613 Traylor Building, Baltimore, MD 21205, USA. kchen21@jhu.edu
- Vascular endothelium expressing endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO), which has a number of important physiological functions in the microvasculature. The rate of NO production by the endothelium is a critical determinant of NO distribution in the vascular wall. We have analyzed the biochemical pathways of NO synthesis and formulated a model to estimate NO production by the microvascular endothelium under physiological conditions. The model quantifies the NO produced by eNOS based on the kinetics of NO synthesis and the availability of eNOS and its intracellular substrates. The predicted NO production from microvessels was in the range of 0.005-0.1 microM/s. This range of predicted values is in agreement with some experimental values but is much lower than other rates previously measured or estimated from experimental data with the help of mathematical modeling. Paradoxical discrepancies between the model predictions and previously reported results based on experimental measurements of NO concentration in the vicinity of the arteriolar wall suggest that NO can also be released through eNOS-independent mechanisms, such as catalysis by neuronal NOS (nNOS). We also used our model to test the sensitivity of NO production to substrate availability, eNOS concentration, and potential rate-limiting factors. The results indicated that the predicted low level of NO production can be attributed primarily to a low expression of eNOS in the microvascular endothelial cells.
Submitter of this revision: administrator
Modellers: administrator, Camille Laibe
Metadata information
isDescribedBy (2 statements)
isVersionOf (1 statement)
occursIn (1 statement)
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
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| BIOMD0000000676_url.xml | SBML L2V4 representation of Chen2006 - Nitric Oxide Release from Endothelial Cells | 74.85 KB | Preview | Download |
Additional files |
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| BIOMD0000000676-biopax2.owl | Auto-generated BioPAX (Level 2) | 27.90 KB | Preview | Download |
| BIOMD0000000676-biopax3.owl | Auto-generated BioPAX (Level 3) | 47.23 KB | Preview | Download |
| BIOMD0000000676.m | Auto-generated Octave file | 9.64 KB | Preview | Download |
| BIOMD0000000676.pdf | Auto-generated PDF file | 187.22 KB | Preview | Download |
| BIOMD0000000676.png | Auto-generated Reaction graph (PNG) | 119.13 KB | Preview | Download |
| BIOMD0000000676.sci | Auto-generated Scilab file | 154.00 Bytes | Preview | Download |
| BIOMD0000000676.svg | Auto-generated Reaction graph (SVG) | 41.35 KB | Preview | Download |
| BIOMD0000000676.vcml | Auto-generated VCML file | 99.78 KB | Preview | Download |
| BIOMD0000000676.xpp | Auto-generated XPP file | 6.55 KB | Preview | Download |
| BIOMD0000000676_urn.xml | Auto-generated SBML file with URNs | 74.79 KB | Preview | Download |
| MODEL1006230005.cps | Curated and annotated COPASI file. | 101.86 KB | Preview | Download |
| MODEL1006230005.sedml | SED-ML file to reproduce figure 2a. Figure 2a was reproduced by plotting NO rate over model time and creating a parameter scan that varied the initial value of Fe3+(eNOS) from 0.015 to 0.045 using 2 intervals. | 2.06 KB | Preview | Download |
- Model originally submitted by : Camille Laibe
- Submitted: Jun 23, 2010 10:11:51 AM
- Last Modified: Feb 21, 2018 2:11:06 PM
Revisions
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Version: 3
- Submitted on: Feb 21, 2018 2:11:06 PM
- Submitted by: administrator
- With comment: Current curated version of Chen2006_NitricOxideRelease
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Version: 2
- Submitted on: Jun 25, 2010 1:06:36 PM
- Submitted by: Camille Laibe
- With comment: Current version of Chen2006_NitricOxideRelease
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Version: 1
- Submitted on: Jun 23, 2010 10:11:51 AM
- Submitted by: Camille Laibe
- With comment: Original import of Chen2006_NitricOxideRelease
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: Variable used inside SBML models
| Species | Initial Concentration/Amount |
|---|---|
| Fe3 Arg iron(3+) ; arginine |
0.0 μmol |
| Fe2 Arg arginine ; iron(2+) |
0.0 μmol |
| Fe3 NO iron(3+) ; nitric oxide |
0.0 μmol |
| Fe2 iron(2+) |
0.0 μmol |
| NO nitric oxide |
0.0 μmol |
| Fe3 enos iron(3+) |
0.015 μmol |
| Fe3 NOHA iron(3+) ; hydroxyarginine |
0.0 μmol |
| Reactions | Rate | Parameters |
|---|---|---|
| Arg + Fe3__enos => Fe3__Arg | Endothelium*(k1*Arg*Fe3__enos-k1_prime*Fe3__Arg) | k1 = 0.1; k1_prime = 0.1 |
| Fe2__Arg => Fe3__O2__Arg; O2 | Endothelium*k5*O2*Fe2__Arg | k5 = 2.58 |
| Fe3__O2__NOHA => Fe3__NO + Citrulline | Endothelium*k11*Fe3__O2__NOHA | k11 = 29.4 |
| Arg + Fe2 => Fe2__Arg | Endothelium*(k4*Arg*Fe2-k4_prime*Fe2__Arg) | k4_prime = 11.4; k4 = 1.89 |
| Fe2__NOHA => Fe2 + NOHA | Endothelium*(k9*Fe2__NOHA-k9_prime*Fe2*NOHA) | k9_prime = 1.89; k9 = 11.4 |
| Fe3__NO => Fe3__enos + NO | Endothelium*k14*Fe3__NO | k14 = 53.9 |
| Fe3__enos => Fe2 | Endothelium*k2*Fe3__enos | k2 = 0.91 |
| Fe2__NO => Fe3__enos; O2 | Endothelium*k13*O2*Fe2__NO | k13 = 0.033 |
| Fe3__O2__Arg => Fe3__NOHA | Endothelium*k6*Fe3__O2__Arg | k6 = 12.6 |
(added: 21 Feb 2018, 14:09:28, updated: 21 Feb 2018, 14:09:28)