Difference between revisions of "Transformation of AA to PGH2 (COX-1)"

From ISMOC
Jump to: navigation, search
(→‎Kmp)
 
(10 intermediate revisions by the same user not shown)
Line 1: Line 1:
 
[[Welcome to the In-Silico Model of Cutaneous Lipids Wiki | Return to overview]]
 
[[Welcome to the In-Silico Model of Cutaneous Lipids Wiki | Return to overview]]
  
−
The COX enzyme possesses two isoforms, COX-1 and COX-2, of which both produce bioactive eicosanoids. The two isoforms have nearly identical active site residues (Simmons et al. 2004), but COX-1 is a constitutive enzyme, whereas COX-2 is an inducible enzyme. Both enzymes add molecular oxygen to arachidonic acid, generating an endoperoxide species, PGH2, by catalysing the two-step reaction of cycloooxygenation and oxygenation, followed by a hydroperoxide reduction.  
+
Cyclooxygenase, COX, also known as prostaglandin endoperoxide H (PGH) synthase, has a broad substrate specificity and is reported to metabolise AA and other fatty acids into prostanoids such as PGs, TXs and prostacyclin <ref>Tsai, Al Wei, C. Baek, H. K. Kulmacz, R. J. Van Wart, H. E., ''Comparison of peroxidase reaction mechanisms of prostaglandin H synthase-1 containing heme and mangano protoporphyrin IX'', J Biol Chem (1997), 272, 8885-94.</ref><ref>Kulmacz, R. J. van der Donk, W. A. Tsai, A. L. , ''Comparison of the properties of prostaglandin H synthase-1 and -2'', Prog Lipid Res (2003), 42, 377-404</ref>. The preferred substrate is AA for both isoforms of COX, COX-1 and COX-2. The COX-1 isoform is constitutively expressed, whereas COX-2 expression is typically negligible in normal cells <ref>Gurram, B. Zhang, S. Li, M. Li, H. Xie, Y. Cui, H. Du, J. Fan, J. Wang, J. Peng, X. , ''Celecoxib conjugated fluorescent probe for identification and discrimination of cyclooxygenase-2 enzyme in cancer cells'', Anal Chem (2018), 90, 5187-5193.</ref> but can be induced in response to inflammatory stimuli, hormones, calcium and growth factors<ref>Fletcher, B. S. Kujubu, D. A. Perrin, D. M. Herschman, H. R. , ''Structure of the mitogen-inducible TIS10 gene and demonstration that the TIS10-encoded protein is a functional prostaglandin G/H synthase'', J Biol Chem (1992), 267, 4338-44.</ref><ref>Xie, W. L. Chipman, J. G. Robertson, D. L. Erikson, R. L. Simmons, D. L. , ''Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing'', Proc Natl Acad Sci U S A (1991), 88, 2692-6.</ref><ref>Ristimaki, A. Garfinkel, S. Wessendorf, J. Maciag, T. Hla, T. , ''Induction of cyclooxygenase-2 by interleukin-1 alpha. Evidence for post-transcriptional regulation'', J Biol Chem (1994), 269, 11769-75.</ref><ref>name, ''title'', journal (year)</ref><ref>Fu, J. Y. Masferrer, J. L. Seibert, K. Raz, A. Needleman, P., ''The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes'', J Biol Chem (1990), 265, 16737-40.</ref><ref>Kujubu, D. A. Reddy, S. T. Fletcher, B. S. Herschman, H. R., ''Expression of the protein product of the prostaglandin synthase-2/TIS10 gene in mitogen-stimulated Swiss 3T3 cells'', J Biol Chem (1993), 268, 5425-30.</ref> <ref>Wang, D. An, S. J. Wang, W. H. McGiff, J. C. Ferreri, N. R., ''CaR-mediated COX-2 expression in primary cultured mTAL cells'', Am J Physiol Renal Physiol (2001), 281, F658-64.)</ref>. Interestingly, basal expression of COX-2 has been found to occur in the kidney, central nervous system, female reproductive organs and stomach <ref>Obermoser, V. Baecker, D. Schuster, C. Braun, V. Kircher, B. Gust, R. , ''Chlorinated cobalt alkyne complexes derived from acetylsalicylic acid as new specific antitumor agents'', Dalton Trans, 47, 4341-4351.</ref><ref>Kirkby, N. S. Chan, M. V. Zaiss, A. K. Garcia-Vaz, E. Jiao, J. Berglund, L. M. Verdu, E. F. Ahmetaj-Shala, B. Wallace, J. L. Herschman, H. R. Gomez, M. F. Mitchell, J. A., ''Systematic study of constitutive cyclooxygenase-2 expression: Role of NF-kappaB and NFAT transcriptional pathways'', Proc Natl Acad Sci U S A (2016), 113, 434-9.</ref>, and frequent expression of COX-2 can be found in the tumorigenic nests of most cancers <ref>Gurram, B. Zhang, S. Li, M. Li, H. Xie, Y. Cui, H. Du, J. Fan, J. Wang, J. Peng, X. , ''Celecoxib conjugated fluorescent probe for identification and discrimination of cyclooxygenase-2 enzyme in cancer cells'', Anal Chem (2018), 90, 5187-5193.</ref><ref>Raj, V. Bhadauria, A. S. Singh, A. K. Kumar, U. Rai, A. Keshari, A. K. Kumar, P. Kumar, D. Maity, B. Nath, S. Prakash, A. Ansari, K. M. Jat, J. L. Saha, S. , ''Novel 1,3,4-thiadiazoles inhibit colorectal cancer via blockade of IL-6/COX-2 mediated JAK2/STAT3 signals as evidenced through data-based mathematical modeling'', Cell, 135, 216-26.</ref>.
 +
 
 +
Both isoforms of COX catalyse a two-step reaction of cycloooxygenation and oxygenation, followed by a hydroperoxide reduction. The cyclooxygenase reaction occurs in the hydrophobic channel within the core of the protein and generates an unstable peroxide intermediate, PGG2. The subsequent peroxidase reaction produces PGH2 and occurs at the heme-containing active site near the protein surface. The two step reaction results in the insertion of molecular oxygen across the C-9 and C-11 double bonds. Both isoforms of COX are heme-containing glycoproteins, that are membrane-bound to the endoplasmic reticulum (ER) and function as homodimers <ref>Smith, W. L. DeWitt, D. L. Garavito, R. M., ''Cyclooxygenases: structural, cellular, and molecular biology'', Annu Rev Biochem (2000), 69, 145-82.</ref><ref>van der Donk, W. A. Tsai, A. L. Kulmacz, R. J., ''The cyclooxygenase reaction mechanism'', Biochemistry, 41, 15451-8.</ref><ref>Rouzer, C. A. Marnett, L. J., ''Mechanism of free radical oxygenation of polyunsaturated fatty acids by cyclooxygenases'', Chem Rev, 103, 2239-304.</ref><ref>Xiao, G. Chen, W. Kulmacz, R. J., ''Comparison of structural stabilities of prostaglandin H synthase-1 and -2'', J Biol Chem (1998), 273, 6801-11.</ref>. Interestingly, in certain tissues COX-1 has been found to colocalises preferentially, but not exclusively, with TXAS, PGFS and cPGES, whereas COX-2 has been found to colocalise with PGIS and mPGES in certain tissues <ref>Miyata, A. Yokoyama, C. Ihara, H. Bandoh, S. Takeda, O. Takahashi, E. Tanabe, T., ''Characterization of the human gene (TBXAS1) encoding thromboxane synthase'', Eur J Biochem (1994), 224, 273-9.</ref><ref>Ullrich, V. Zou, M. H. Bachschmid, M. , ''New physiological and pathophysiological aspects on the thromboxane A(2)-prostacyclin regulatory system'', Biochim Biophys Acta (2001), 1532, 1-14.</ref><ref>Smyth, E. M. Grosser, T. Wang, M. Yu, Y. FitzGerald, G. A., ''Prostanoids in health and disease'', J Lipid Res, 50 Suppl, S423-8.</ref><ref>Smith, W. L. DeWitt, D. L. Garavito, R. M., ''Cyclooxygenases: structural, cellular, and molecular biology'', Annu Rev Biochem (2000), 69, 145-82.</ref><ref>Ueno, N. Murakami, M. Tanioka, T. Fujimori, K. Tanabe, T.
 +
Urade, Y. Kudo, I. , ''Coupling between cyclooxygenase, terminal prostanoid synthase, and phospholipase A2'', J Biol Chem (2001), 276, 34918-27.</ref>.
  
−
PGH2 possesses a short life time due to the formation of a reactive functional group. The endoperoxide undergoes rapid isomerisation reactions, catalysed by a series of synthase enzymes (PGES, PGDS, PGIS, PGFS and TXAS). The resultant species of the isomerisation reactions are PGs (PGE2, PGD2, PGJ2, deoxy-PGJ2 and PGF2α), TXs (TXA2 and TXB2) and prostacyclin (PGI2), all of which have varying effects on the immune system.
 
  
 
== Reaction ==
 
== Reaction ==
Line 26: Line 28:
 
! Species
 
! Species
 
! Notes
 
! Notes
 +
! Weight
 
! Reference
 
! Reference
 
|-
 
|-
Line 36: Line 39:
 
Temperature: 298.15 K
 
Temperature: 298.15 K
 
Pressure: 1 bar
 
Pressure: 1 bar
 +
|64
 
|<ref name="Silva2003”>[http://link.springer.com/article/10.1007/s00214-003-0476-9 P. Silva, "A theoretical study of radical-only and combined radical/carbocationic mechanisms of arachidonic acid cyclooxygenation by prostaglandin H synthase" Theor Chem Acc (2003) 110: 345]</ref>
 
|<ref name="Silva2003”>[http://link.springer.com/article/10.1007/s00214-003-0476-9 P. Silva, "A theoretical study of radical-only and combined radical/carbocationic mechanisms of arachidonic acid cyclooxygenation by prostaglandin H synthase" Theor Chem Acc (2003) 110: 345]</ref>
 
|-
 
|-
Line 58: Line 62:
 
! Species
 
! Species
 
! Notes
 
! Notes
 +
! Weight
 
! Reference
 
! Reference
 
|-
 
|-
Line 67: Line 72:
 
pH: 7.6 - 8.4
 
pH: 7.6 - 8.4
 
Temperature: 37 °C
 
Temperature: 37 °C
 +
|2048
 
|<ref name="Noreen1998"> [http://pubs.acs.org/doi/abs/10.1021/np970343j Y. ''Noreen Development of a Radiochemical Cyclooxygenase-1 and -2 in Vitro Assay for Identification of Natural Products as Inhibitors of Prostaglandin Biosynthesis''J. Nat. Prod., 1998, 61 (1), pp 2–7)]</ref>
 
|<ref name="Noreen1998"> [http://pubs.acs.org/doi/abs/10.1021/np970343j Y. ''Noreen Development of a Radiochemical Cyclooxygenase-1 and -2 in Vitro Assay for Identification of Natural Products as Inhibitors of Prostaglandin Biosynthesis''J. Nat. Prod., 1998, 61 (1), pp 2–7)]</ref>
 
|-
 
|-
Line 76: Line 82:
 
pH: 8
 
pH: 8
 
Temperature: 30 ± 0.2 °C
 
Temperature: 30 ± 0.2 °C
 +
|192
 
|<ref name="Mukherjee2007"> [http://pubs.acs.org/doi/abs/10.1021/bi602502jA. Mukherjee ''Molecular Oxygen Dependent Steps in Fatty Acid Oxidation by Cyclooxygenase-1'' Biochemistry, 2007, 46 (13), pp 3975–3989]</ref>
 
|<ref name="Mukherjee2007"> [http://pubs.acs.org/doi/abs/10.1021/bi602502jA. Mukherjee ''Molecular Oxygen Dependent Steps in Fatty Acid Oxidation by Cyclooxygenase-1'' Biochemistry, 2007, 46 (13), pp 3975–3989]</ref>
 
|}
 
|}
Line 89: Line 96:
  
 
=== K<sub>mp</sub> ===
 
=== K<sub>mp</sub> ===
−
In this model some parameters are referred as “Dependent parameters”, meaning that the log-normal distribution for that parameter was calculated using multivariate distributions  (discussed in [[Quantification of parameter uncertainty | Protocol for defining informative priors for ensemble modelling in systems biology]]). As a result, no confidence interval factor or literature values were cited for the Dependent parameters.
+
This is a “Dependent parameter”, meaning that the log-normal distribution for this parameter was calculated using multivariate distributions  (this is discussed in detail[[Quantification of parameter uncertainty | here]]). As a result, no confidence interval factor or literature values were cited for this parameter.
  
 
{| class="wikitable"
 
{| class="wikitable"
Line 108: Line 115:
 
! Species
 
! Species
 
! Notes
 
! Notes
 +
! Weight
 
! Reference
 
! Reference
 
|-
 
|-
Line 117: Line 125:
 
pH: 8
 
pH: 8
 
Temperature: 30 ± 0.2 °C
 
Temperature: 30 ± 0.2 °C
 +
|192
 
|<ref name="Mukherjee2007"> [http://pubs.acs.org/doi/abs/10.1021/bi602502jA. Mukherjee ''Molecular Oxygen Dependent Steps in Fatty Acid Oxidation by Cyclooxygenase-1'' Biochemistry, 2007, 46 (13), pp 3975–3989]</ref>
 
|<ref name="Mukherjee2007"> [http://pubs.acs.org/doi/abs/10.1021/bi602502jA. Mukherjee ''Molecular Oxygen Dependent Steps in Fatty Acid Oxidation by Cyclooxygenase-1'' Biochemistry, 2007, 46 (13), pp 3975–3989]</ref>
 
|-
 
|-
Line 132: Line 141:
  
 
=== Enzyme concentration ===
 
=== Enzyme concentration ===
 +
 +
To convert the enzyme concentration from ppm to mM, the following [[Common equations#Enzyme concentration (mM)|equation]] was used.
  
 
{|class="wikitable sortable"  
 
{|class="wikitable sortable"  
Line 140: Line 151:
 
! Species
 
! Species
 
! Notes
 
! Notes
 +
! Weight
 
! Reference
 
! Reference
−
|-
 
−
|1176
 
−
|<math> ppm </math>
 
−
|Human
 
−
|Expression Vector: Urinary Bladder
 
−
Enzyme: Cyclooxygenase-1 (PGTS1)
 
−
pH: 7.5
 
−
Temperature: 37 °C
 
−
|<ref name="Kim2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13302.pdf M. Kim ''A draft map of the human proteome'' Nature, 2014 509, 575–581]</ref>
 
 
|-
 
|-
 
|849
 
|849
Line 158: Line 161:
 
pH: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
Temperature: 37 °C
 +
|1024
 
|<ref name="Kim2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13302.pdf M. Kim ''A draft map of the human proteome'' Nature, 2014 509, 575–581]</ref>
 
|<ref name="Kim2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13302.pdf M. Kim ''A draft map of the human proteome'' Nature, 2014 509, 575–581]</ref>
 
|-
 
|-
Line 167: Line 171:
 
pH: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
Temperature: 37 °C
 +
|1024
 
|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the
 
|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the
 
human proteome'' Nature, 2014 509, 582–587]</ref>
 
human proteome'' Nature, 2014 509, 582–587]</ref>
Line 177: Line 182:
 
pH: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
Temperature: 37 °C
 +
|1024
 
|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the
 
|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the
 
human proteome'' Nature, 2014 509, 582–587]</ref>
 
human proteome'' Nature, 2014 509, 582–587]</ref>
Line 187: Line 193:
 
pH: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
Temperature: 37 °C
 +
|1024
 
|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the
 
|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the
 
human proteome'' Nature, 2014 509, 582–587]</ref>
 
human proteome'' Nature, 2014 509, 582–587]</ref>
Line 197: Line 204:
 
pH: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
Temperature: 37 °C
 +
|1024
 
|<ref name="Kim2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13302.pdf M. Kim ''A draft map of the human proteome'' Nature, 2014 509, 575–581]</ref>
 
|<ref name="Kim2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13302.pdf M. Kim ''A draft map of the human proteome'' Nature, 2014 509, 575–581]</ref>
 
|-
 
|-
Line 203: Line 211:
 
{| class="wikitable"
 
{| class="wikitable"
 
|+  style="text-align: left;" | Description of the COX-1 concentration distribution
 
|+  style="text-align: left;" | Description of the COX-1 concentration distribution
−
! Mode (mM) !! Confidence Interval  !! Location parameter (μ) !! Scale parameter (σ)
+
! Mode (ppm) !! Mode (mM) !! Confidence Interval  !! Location parameter (μ) !! Scale parameter (σ)
 
|-
 
|-
−
| 4.18E+28 || 1.00E+01 || 6.67E+01 || 8.90E-01
+
| 129 || 7.14E-04 || 1.00E+01 || 6.67E+01 || 8.90E-01
 
|}
 
|}
 +
 +
  
 
[[Image:154.jpg|none|thumb|500px|The estimated probability distribution for COX-1 concentration. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale.  ]]
 
[[Image:154.jpg|none|thumb|500px|The estimated probability distribution for COX-1 concentration. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale.  ]]

Latest revision as of 15:41, 20 August 2019

Return to overview

Cyclooxygenase, COX, also known as prostaglandin endoperoxide H (PGH) synthase, has a broad substrate specificity and is reported to metabolise AA and other fatty acids into prostanoids such as PGs, TXs and prostacyclin [1][2]. The preferred substrate is AA for both isoforms of COX, COX-1 and COX-2. The COX-1 isoform is constitutively expressed, whereas COX-2 expression is typically negligible in normal cells [3] but can be induced in response to inflammatory stimuli, hormones, calcium and growth factors[4][5][6][7][8][9] [10]. Interestingly, basal expression of COX-2 has been found to occur in the kidney, central nervous system, female reproductive organs and stomach [11][12], and frequent expression of COX-2 can be found in the tumorigenic nests of most cancers [13][14].

Both isoforms of COX catalyse a two-step reaction of cycloooxygenation and oxygenation, followed by a hydroperoxide reduction. The cyclooxygenase reaction occurs in the hydrophobic channel within the core of the protein and generates an unstable peroxide intermediate, PGG2. The subsequent peroxidase reaction produces PGH2 and occurs at the heme-containing active site near the protein surface. The two step reaction results in the insertion of molecular oxygen across the C-9 and C-11 double bonds. Both isoforms of COX are heme-containing glycoproteins, that are membrane-bound to the endoplasmic reticulum (ER) and function as homodimers [15][16][17][18]. Interestingly, in certain tissues COX-1 has been found to colocalises preferentially, but not exclusively, with TXAS, PGFS and cPGES, whereas COX-2 has been found to colocalise with PGIS and mPGES in certain tissues [19][20][21][22][23].


Reaction

R2 AA-PGH2.jpg

Chemical equation

AA \rightleftharpoons PGH2

Rate equation

R65.PNG

Enzyme Parameters

Keq

Literature values
Value Units Species Notes Weight Reference
(-30) kcal/mol Unspecified Calculations with a Gaussian98 suite of programs

Enzyme: COX (Unspecific) Substrate: Arachidonate Temperature: 298.15 K Pressure: 1 bar

64 [24]
Description of the COX-1 Keq distribution
Mode Confidence Interval Location parameter (µ) Scale parameter (σ)
4.18E+28 1.00E+01 6.67E+01 8.90E-01
The estimated probability distribution for COX-1 Keq. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale.

Kms

Literature values
Value Units Species Notes Weight Reference
0.0088 ± 0.0022 mM Human Expression Vector: Human

Enzyme: Cyclooxygenase-1 pH: 7.6 - 8.4 Temperature: 37 °C

2048 [25]
0.0019 ± 0.0002 mM Ram Expression Vector: Ram

Enzyme: Cyclooxygenase-1 pH: 8 Temperature: 30 ± 0.2 °C

192 [26]
Description of the COX-1 Kms distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
8.30E-03 1.62E+00 -4.60E+00 4.41E-01
The estimated probability distribution for COX-1 Kms. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale.

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.

Description of the COX-1 Kmp distribution
Mode (mM) Location parameter (μ) Scale parameter (σ)
8.20E-03 -4.60E+00 4.49E-01
The estimated probability distribution for COX-1 Kmp. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale.

kcat

Literature values
Value Units Species Notes Weight Reference
8820 ± 360 per minute Ram Expression Vector: Ram

Enzyme: Cyclooxygenase-1 pH: 8 Temperature: 30 ± 0.2 °C

192 [26]
Description of the COX-1 kcat distribution
Mode (min-1) Confidence Interval Location parameter (μ) Scale parameter (σ)
8.81E+03 1.04E+00 9.09E+00 4.08E-02
The estimated probability distribution for COX-1 Kmp. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale.

Enzyme concentration

To convert the enzyme concentration from ppm to mM, the following equation was used.

Literature values
Value Units Species Notes Weight Reference
849 ppm Human Expression Vector: Platlet

Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C

1024 [27]
208 ppm Human Expression Vector: Stomach

Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C

1024 [28]
130 ppm Human Expression Vector: Esophagus

Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C

1024 [28]
70.8 ppm Human Expression Vector: Oral Cavity

Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C

1024 [28]
19.1 ppm Human Expression Vector: Lung

Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C

1024 [27]
Description of the COX-1 concentration distribution
Mode (ppm) Mode (mM) Confidence Interval Location parameter (μ) Scale parameter (σ)
129 7.14E-04 1.00E+01 6.67E+01 8.90E-01


The estimated probability distribution for COX-1 concentration. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale.

References

  1. ↑ Tsai, Al Wei, C. Baek, H. K. Kulmacz, R. J. Van Wart, H. E., Comparison of peroxidase reaction mechanisms of prostaglandin H synthase-1 containing heme and mangano protoporphyrin IX, J Biol Chem (1997), 272, 8885-94.
  2. ↑ Kulmacz, R. J. van der Donk, W. A. Tsai, A. L. , Comparison of the properties of prostaglandin H synthase-1 and -2, Prog Lipid Res (2003), 42, 377-404
  3. ↑ Gurram, B. Zhang, S. Li, M. Li, H. Xie, Y. Cui, H. Du, J. Fan, J. Wang, J. Peng, X. , Celecoxib conjugated fluorescent probe for identification and discrimination of cyclooxygenase-2 enzyme in cancer cells, Anal Chem (2018), 90, 5187-5193.
  4. ↑ Fletcher, B. S. Kujubu, D. A. Perrin, D. M. Herschman, H. R. , Structure of the mitogen-inducible TIS10 gene and demonstration that the TIS10-encoded protein is a functional prostaglandin G/H synthase, J Biol Chem (1992), 267, 4338-44.
  5. ↑ Xie, W. L. Chipman, J. G. Robertson, D. L. Erikson, R. L. Simmons, D. L. , Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing, Proc Natl Acad Sci U S A (1991), 88, 2692-6.
  6. ↑ Ristimaki, A. Garfinkel, S. Wessendorf, J. Maciag, T. Hla, T. , Induction of cyclooxygenase-2 by interleukin-1 alpha. Evidence for post-transcriptional regulation, J Biol Chem (1994), 269, 11769-75.
  7. ↑ name, title, journal (year)
  8. ↑ Fu, J. Y. Masferrer, J. L. Seibert, K. Raz, A. Needleman, P., The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes, J Biol Chem (1990), 265, 16737-40.
  9. ↑ Kujubu, D. A. Reddy, S. T. Fletcher, B. S. Herschman, H. R., Expression of the protein product of the prostaglandin synthase-2/TIS10 gene in mitogen-stimulated Swiss 3T3 cells, J Biol Chem (1993), 268, 5425-30.
  10. ↑ Wang, D. An, S. J. Wang, W. H. McGiff, J. C. Ferreri, N. R., CaR-mediated COX-2 expression in primary cultured mTAL cells, Am J Physiol Renal Physiol (2001), 281, F658-64.)
  11. ↑ Obermoser, V. Baecker, D. Schuster, C. Braun, V. Kircher, B. Gust, R. , Chlorinated cobalt alkyne complexes derived from acetylsalicylic acid as new specific antitumor agents, Dalton Trans, 47, 4341-4351.
  12. ↑ Kirkby, N. S. Chan, M. V. Zaiss, A. K. Garcia-Vaz, E. Jiao, J. Berglund, L. M. Verdu, E. F. Ahmetaj-Shala, B. Wallace, J. L. Herschman, H. R. Gomez, M. F. Mitchell, J. A., Systematic study of constitutive cyclooxygenase-2 expression: Role of NF-kappaB and NFAT transcriptional pathways, Proc Natl Acad Sci U S A (2016), 113, 434-9.
  13. ↑ Gurram, B. Zhang, S. Li, M. Li, H. Xie, Y. Cui, H. Du, J. Fan, J. Wang, J. Peng, X. , Celecoxib conjugated fluorescent probe for identification and discrimination of cyclooxygenase-2 enzyme in cancer cells, Anal Chem (2018), 90, 5187-5193.
  14. ↑ Raj, V. Bhadauria, A. S. Singh, A. K. Kumar, U. Rai, A. Keshari, A. K. Kumar, P. Kumar, D. Maity, B. Nath, S. Prakash, A. Ansari, K. M. Jat, J. L. Saha, S. , Novel 1,3,4-thiadiazoles inhibit colorectal cancer via blockade of IL-6/COX-2 mediated JAK2/STAT3 signals as evidenced through data-based mathematical modeling, Cell, 135, 216-26.
  15. ↑ Smith, W. L. DeWitt, D. L. Garavito, R. M., Cyclooxygenases: structural, cellular, and molecular biology, Annu Rev Biochem (2000), 69, 145-82.
  16. ↑ van der Donk, W. A. Tsai, A. L. Kulmacz, R. J., The cyclooxygenase reaction mechanism, Biochemistry, 41, 15451-8.
  17. ↑ Rouzer, C. A. Marnett, L. J., Mechanism of free radical oxygenation of polyunsaturated fatty acids by cyclooxygenases, Chem Rev, 103, 2239-304.
  18. ↑ Xiao, G. Chen, W. Kulmacz, R. J., Comparison of structural stabilities of prostaglandin H synthase-1 and -2, J Biol Chem (1998), 273, 6801-11.
  19. ↑ Miyata, A. Yokoyama, C. Ihara, H. Bandoh, S. Takeda, O. Takahashi, E. Tanabe, T., Characterization of the human gene (TBXAS1) encoding thromboxane synthase, Eur J Biochem (1994), 224, 273-9.
  20. ↑ Ullrich, V. Zou, M. H. Bachschmid, M. , New physiological and pathophysiological aspects on the thromboxane A(2)-prostacyclin regulatory system, Biochim Biophys Acta (2001), 1532, 1-14.
  21. ↑ Smyth, E. M. Grosser, T. Wang, M. Yu, Y. FitzGerald, G. A., Prostanoids in health and disease, J Lipid Res, 50 Suppl, S423-8.
  22. ↑ Smith, W. L. DeWitt, D. L. Garavito, R. M., Cyclooxygenases: structural, cellular, and molecular biology, Annu Rev Biochem (2000), 69, 145-82.
  23. ↑ Ueno, N. Murakami, M. Tanioka, T. Fujimori, K. Tanabe, T. Urade, Y. Kudo, I. , Coupling between cyclooxygenase, terminal prostanoid synthase, and phospholipase A2, J Biol Chem (2001), 276, 34918-27.
  24. ↑ P. Silva, "A theoretical study of radical-only and combined radical/carbocationic mechanisms of arachidonic acid cyclooxygenation by prostaglandin H synthase" Theor Chem Acc (2003) 110: 345
  25. ↑ Y. Noreen Development of a Radiochemical Cyclooxygenase-1 and -2 in Vitro Assay for Identification of Natural Products as Inhibitors of Prostaglandin BiosynthesisJ. Nat. Prod., 1998, 61 (1), pp 2–7)
  26. ↑ 26.0 26.1 Mukherjee Molecular Oxygen Dependent Steps in Fatty Acid Oxidation by Cyclooxygenase-1 Biochemistry, 2007, 46 (13), pp 3975–3989
  27. ↑ 27.0 27.1 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
  28. ↑ 28.0 28.1 28.2 [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587]

Related Reactions

Retrieved from ‘http://www.systemsbiology.ls.manchester.ac.uk/wiki/index.php?title=Transformation_of_AA_to_PGH2_(COX-1)&oldid=7468’