Difference between revisions of "Transformation of PGF2a to exPGF2a"

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[[ATP-Binding Cassette Transporters|Return to ATP-Binding Cassette Transporters]]  
 
[[ATP-Binding Cassette Transporters|Return to ATP-Binding Cassette Transporters]]  
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Transport – The transport systems relevant to each eicosanoid have not yet been fully characterised, therefore an ATP-binding cassette transporter has been assumed as the method of transportation across the cellular membrane for reactions. As there is no known data about the eicosanoid selectivity of the transporter, the Michaelis Menten constant (Km) and catalytic activity (kcat) are currently the same for each substrate.
 
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Transport Assumptions: Rate of ATP hydrolysis is much faster than lipid transport, therefore the kcat of ATP hydrolysis was assigned as (0.0009 per second), whereas ABC transporter is 0.19 per second.  Temperature was set to 310 K (physiological condition) and the Gibbs free energy is corrected for physiological conditions from -36 kJ/mol to -50 kJ/mol. The ATP/ADP ratio was set at 2 (ref Bies1975).
 
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== Rate equation ==
 
== Rate equation ==

Revision as of 09:54, 17 May 2019

Return to overview

Return to ATP-Binding Cassette Transporters

Rate equation

R22.PNG

Transport Parameters

Kms

Literature values
Value Units Species Notes Reference
0.0109 ± 0.0041 mM Human Substrate: LTC4

pH 7.0, 37°C, recombinant MRP2, using 4mM MgATP and 5g of isolated membranes.

[1]
0.0000366 ± 0.0000038 mM Human Substrate LTC4, 37 °C, 4 mM ATP, [2]
5.3E-3 ± 2.6E-3 mM Human 4 mM ATP, 37°C, 5–10 ml of membrane vesicle suspension (30

mg protein).

[3]
0.1954 ± 0.0612 mM Human pH 7.0, 37°C, recombinant MRP2,

Substrate: 17beta-estradiol 17-(beta-D-glucuronide)

[1]
0.1097 ± 0.0391 mM Human pH 7.0, 37°C, recombinant MRP2,

Substrate: Estrone glucuronide

[1]
0.0207 mM Human pH 7.4, 37°C, Substrate: Progesterone, Expression vector: Human HepG2 hepatoma [4]
Description of the ABC Kms distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.13E+01 1.00E+01 3.22E+00 8.91E-01
The estimated probability distribution for ABC 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.

kcat

No data available on the turnover of ABCC4 transporter therefore based upon estimates made by http://book.bionumbers.org/what-are-the-rates-of-membrane-transporters/

Literature values
Value Units Transporter Notes Reference
3.5 min-1 Glucose transporter ptsI Organism: Bacteria Escherichia coli

Back of the envelope calculation by BioNumbers: http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=102931

[5]
0.33 - 0.83 min-1 Rate of transport of H+/Lactose transporter Organism: Bacteria Escherichia coli

Back of the envelop calculation on bionumbers http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=103159

[6]
3.28 min-1 Catalytic Rate of transporter HXT7 Organism: Budding yeast Saccharomyces cerevisiae

Back of the envelope calculation http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=101737

[7]
11.34 min-1 Human pH 7.0, 37°C, recombinant MRP2,

Substrate: Estrone glucuronide

[1]
Description of the ABC kcat distribution
Mode (min-1) Confidence Interval Location parameter (µ) Scale parameter (σ)
2.10E-02 2.37E+01 -2.60E+00 1.12E+00
The estimated probability distribution for ABC kcat. 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.

Vmax

Literature values
Value Units Species Notes Reference
0.00019 ± 1.96e-5 mmol/min/mg protein Human Substrate: LTC4

pH 7.0, 37°C, recombinant MRP2, using 4mM MgATP and 5g of isolated membranes.

[1]
1.25e-7 ± 1.2e-8 mmol/min/mg Human Substrate LTC4, 37 °C, 4 mM ATP, [2]
2.02e-8 ± 5.9e-9 mmol/mg/min Human 4 mM ATP, 37°C, 5–10 ml of membrane vesicle suspension (30

mg protein).

[3]

Transporter concentration

Literature values
Value Units Species Notes Reference
5.15 ppm Human Expression Vector: Stomach

Enzyme: ABCC4 pH: 7.5 Temperature: 37 °C

[8]
5.94 ppm Human Expression Vector: Lung

Enzyme: ABCC4 pH: 7.5 Temperature: 37 °C

[9]
2.66 ppm Human Expression Vector: Gut

Enzyme: ABCC4 pH: 7.5 Temperature: 37 °C

[9]
Description of the ABC concentration distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
5.06E+00 1.44E+00 1.74E+00 3.42E-01
The estimated probability distribution for ABC 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. ↑ 1.0 1.1 1.2 1.3 1.4 Yasunaga M. "Molecular cloning and functional characterization of cynomolgus monkey multidrug resistance-associated protein 2 (MRP2) Eur. J. Pharm. Sci. 35, 326-334 (2008)
  2. ↑ 2.0 2.1 Zeng H. "Transport of amphipathic anions by human multidrug resistance protein 3 J. Biol. Chem. 275, 34166-34172 (2000) Cite error: Invalid <ref> tag; name "Mao2000" defined multiple times with different content
  3. ↑ 3.0 3.1 "Functional reconstitution of substrate transport by purified multidrug resistance protein MRP1 (ABCC1) in phospholipid vesicles Cancer Res. 60, 4779-4784 (2000)
  4. ↑ W. Fong "Schisandrol A from Schisandra chinensis Reverses P-Glycoprotein-Mediated Multidrug Resistance by Affecting Pgp-Substrate Complexes Planta Med 2007; 73(3): 212-220
  5. ↑ Waygood EB Enzyme I of the phosphoenolpyruvate: sugar phosphotransferase system of Escherichia coli. Purification to homogeneity and some properties.Can J Biochem. 1980 Jan;58(1):40-8.
  6. ↑ Naftalin R. J. ELactose permease H+-lactose symporter: mechanical switch or Brownian ratchet?Biophys J. 2007 May 15;92(10):3474-91. Epub 2007 Feb 26.
  7. ↑ Ye L. Expression and activity of the Hxt7 high-affinity hexose transporter of Saccharomyces cerevisiaeYeast. 2001 Sep 30;18(13):1257-67.
  8. ↑ M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587
  9. ↑ 9.0 9.1 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
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