Difference between revisions of "Transformation of AA to exAA"

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(→‎Transport Parameters)
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== Transport Parameters ==
 
== Transport Parameters ==
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===K<sub>ms</sub>===
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In this model numerous simplifications have been made and as a result, metabolites, such as AA, occur in higher concentrations than are found in reality. To prevent a large percentage of AA being exported before it is metabolised, the Km of the ABC transporter has been increased (mode= 25 mM, CIF=10, µ = 4.01, σ = 0.89).
 
{|class="wikitable sortable"  
 
{|class="wikitable sortable"  
−
|+  style="text-align: left;" | Michaelis-Menten Constants
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|+  style="text-align: left;" | Literature values
 
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|-
 
! Value
 
! Value
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|-
 
|-
 
|}
 
|}
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{| class="wikitable"
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|+  style="text-align: left;" | Description of the ABC kcat distribution
 +
! Mode (mM) !! Confidence Interval  !! Location parameter (µ) !! Scale parameter (σ)
 +
|-
 +
| 1.13E+01 || 1.00E+01 || 3.22E+00 || 8.91E-01
 +
|}
 +
 +
 +
[[Image:129_-_v2.jpg|none|thumb|500px|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.  ]]
  
  
 +
=== k<sub>cat</sub>===
 
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/
 
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/
 
{|class="wikitable sortable"  
 
{|class="wikitable sortable"  
−
|+  style="text-align: left;" | Turnover Number
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|+  style="text-align: left;" | Literature values
 
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|-
 
! Value
 
! Value
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Back of the envelope calculation http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=101737
 
Back of the envelope calculation http://bionumbers.hms.harvard.edu/bionumber.aspx?&id=101737
 
|<ref name="Ye2001"> [https://www.ncbi.nlm.nih.gov/pubmed/11561293?dopt=Abstract Ye L. ''Expression and activity of the Hxt7 high-affinity hexose transporter of Saccharomyces cerevisiae''Yeast. 2001 Sep 30;18(13):1257-67.]</ref>
 
|<ref name="Ye2001"> [https://www.ncbi.nlm.nih.gov/pubmed/11561293?dopt=Abstract Ye L. ''Expression and activity of the Hxt7 high-affinity hexose transporter of Saccharomyces cerevisiae''Yeast. 2001 Sep 30;18(13):1257-67.]</ref>
 +
|-
 +
|11.34
 +
|min-1
 +
|Human
 +
|pH 7.0, 37°C, recombinant MRP2,
 +
Substrate: Estrone glucuronide
 +
|<ref name="Yas2007"> [http://ac.els-cdn.com/S0928098708003618/1-s2.0-S0928098708003618-main.pdf?_tid=a147bd90-1dc8-11e6-9405-00000aab0f26&acdnat=1463666001_5a08a971497da36ce8a604f84caadfc2 Yasunaga M. "Molecular cloning and functional characterization of cynomolgus monkey multidrug resistance-associated protein 2 (MRP2)''  Eur. J. Pharm. Sci. 35, 326-334 (2008)]</ref>
 
|-
 
|-
 
|}
 
|}
  
 +
{| class="wikitable"
 +
|+  style="text-align: left;" | Description of the ABC Kms distribution
 +
! Mode (min-1) !! Confidence Interval  !! Location parameter (µ) !! Scale parameter (σ)
 +
|-
 +
| 2.10E-02 || 2.37E+01 || -2.60E+00 || 1.12E+00
 +
|}
 +
 +
[[Image:abc kcat.jpg|none|thumb|500px|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.  ]]
 +
 +
===V<sub>max</sub>===
 
{|class="wikitable sortable"  
 
{|class="wikitable sortable"  
−
|+  style="text-align: left;" | Vmax ***
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|+  style="text-align: left;" | Literature values
 
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|-
 
! Value
 
! Value
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|}
  
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=== Transporter concentration ===
 
{|class="wikitable sortable"  
 
{|class="wikitable sortable"  
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|+  style="text-align: left;" | Abundance
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|+  style="text-align: left;" | Literature values
 
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! Value
 
! Value
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|-
 
|-
 
|}
 
|}
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{| class="wikitable"
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|+  style="text-align: left;" | 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
 +
|}
 +
 +
[[Image:153.jpg|none|thumb|500px|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 ==
 
== References ==
 
<references/>
 
<references/>

Revision as of 09:27, 16 May 2019

Return to overview

Return to ATP-Binding Cassette Transporters


Rate equation

R42.PNG

Transport Parameters

Kms

In this model numerous simplifications have been made and as a result, metabolites, such as AA, occur in higher concentrations than are found in reality. To prevent a large percentage of AA being exported before it is metabolised, the Km of the ABC transporter has been increased (mode= 25 mM, CIF=10, µ = 4.01, σ = 0.89).

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 kcat 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 Kms 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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