Transformation of PGH2 to TXA2
The isomerisation of PGH2 to TXA2 is performed by thromboxane A synthase (TXAS). This reaction includes the rearrangement of the peroxide functional group by the protein’s heme group, whereby one oxygen is incorporated into the cyclopentane ring between C11 and C12 to form a tetrahydropyran ring, whilst the other oxygen forms a trimethylene oxide ring across the tetrahydropyran ring between C9 and C11.
Contents
Reaction
Chemical equation
Rate equation
Parameters
Kms
Value | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
4.00E-03 | Human | Expression Vector: Human Monocyte
Enzyme: Platelet Free Human Monocyte pH: 7.4 Temperature: 37 |
2048 | [1] | |
1.00E-02 | Human | Expression Vector: Human mirosome
Enzyme: Human Thromboxane Synthase pH:7.4 Temperature: |
512 | [2] | |
2.20E-02 | Human | Expression Vector:Human platelet
Enzyme: Human thromboxane synthase pH: 7.4 Temperature: 37 |
2048 | [3] |
Mode (mM) | Confidence Interval | Location parameter (µ) | Scale parameter (σ) |
---|---|---|---|
9.96E-03 | 2.25E+00 | -3.9721 | 0.78374 |
Kmp
This is a “Dependent parameter”, meaning that the log-normal distribution for this parameter was calculated using multivariate distributions (this is discussed in detail here). As a result, no confidence interval factor or literature values were cited for this parameter.
Mode (mM) | Location parameter (µ) | Scale parameter (σ) |
---|---|---|
1.03E-02 | -3.942048511 | 0.797944323 |
kcat
Value | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
2687 | per minute | Human | Expression Vector: Human Platelets
Enzyme: TXAS pH: 7.4 Temperature:30 |
512 | [4] |
1628 | per minute | Human | Expression Vector:Platelet Microsomes
Enzyme: TXAS pH:7.4 Temperature:37 |
2048 | [5] |
Mode (min-1) | Confidence Interval | Location parameter (µ) | Scale parameter (σ) |
---|---|---|---|
1.67E+03 | 1.25E+00 | 7.467597712 | 0.216816683 |
Enzyme concentration
To convert the enzyme concentration from ppm to mM, the following equation was used.
Value | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
949 | Human | Expression Vector: Platelet
Enzyme: TXAS pH: 7.5 Temperature: 37 °C |
1024 | [6] | |
56.2 | Human | Expression Vector: Lung
Enzyme: TXAS pH: 7.5 Temperature: 37 °C |
1024 | [6] | |
4.58 | Human | Expression Vector: Urinary Bladder
Enzyme: TXAS pH: 7.5 Temperature: 37 °C |
1024 | [6] | |
101 | Human | Expression Vector: Oral Cavity
Enzyme: TXAS pH: 7.5 Temperature: 37 °C |
1024 | [7] |
Mode (ppm) | Mode (mM) | Confidence Interval | Location parameter (µ) | Scale parameter (σ) |
---|---|---|---|---|
7.50E+01 | 4.15E-04 | 6.69E+00 | 5.66E+00 | 1.16E+00 |
Keq
Value | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
41.08 | kcal/mol | Not stated | Estimated
Enzyme: TXAS Substrate: Arachidonate Product: TXA2 pH: 7.3 ionic strength: 0.25 |
64 | [8] |
Mode | Confidence Interval | Location parameter (µ) | Scale parameter (σ) |
---|---|---|---|
9.35E-01 | 1.00E+01 | 7.30E-01 | 8.90E-01 |
References
- ↑ M. Orlandi, G. Bartolini, Thromboxane A2 synthase activity in platelet free human monocytes. Biochim Biophys Acta. 1994 Dec 8;1215(3):285-90.
- ↑ R. Nusing, S. Schneider-Voss and V. Ullrich, Immunoaffinity purification of human thromboxane synthase. Arch Biochem Biophys. 1990 Aug 1;280(2):325-30.
- ↑ Hecker M. On the mechanism of prostacyclin and thromboxane A2 biosynthesis.J Biol Chem. 1989 Jan 5;264(1):141-50.
- ↑ [www.ncbi.nlm.nih.gov/pubmed/3579292 Hecker M. “Products, kinetics, and substrate specificity of homogeneous thromboxane synthase from human platelets: Development of a novel enzyme assay ” Arch. Biochem. Biophys. 1987, 254, 124-135]
- ↑ [www.ncbi.nlm.nih.gov/pubmed/2999104 Haurand M. “Isolation and characterization of thromboxane synthase from human platelets as a cytochrome P-450 enzyme” J Biol Chem. 1985, 260 (5), 15059-15067]
- ↑ 6.0 6.1 6.2 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
- ↑ M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587
- ↑ Caspi et al 2014, "The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases," Nucleic Acids Research 42:D459-D471