Difference between revisions of "Transformation of PGE2 to 15-Keto-PGE2"

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(→‎15-PGDH Parameters)
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[[File:R66.PNG|center|500px]]
 
[[File:R66.PNG|center|500px]]
  
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== 15-PGDH Parameters ==
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== Enzyme Parameters ==
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=== K<sub>ms</sub>===
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{|class="wikitable sortable"  
 
{|class="wikitable sortable"  
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|+  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"
 +
|+  style="text-align: left;" | Description of the 15-PGDH Kms distribution
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! Mode (mM) !! Confidence Interval  !! Location parameter (μ) !! Scale parameter (σ)
 +
|-
 +
| 7.64E-03 || 5.05E+00 || -4.41E+00 || 6.80E-01
 +
|}
 +
 +
[[Image:73.jpg|none|thumb|500px|The estimated probability distribution for 15-PGDH 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.  ]]
  
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===K<sub>mp</sub>===
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{| class="wikitable"
 +
|+  style="text-align: left;" | Description of the 15-PGDH Kmp distribution
 +
! Mode (mM) !! Location parameter (μ) !! Scale parameter (σ)
 +
|-
 +
| 7.70E-03  || -4.41E+00 || 6.72E-01
 +
|}
 +
 +
[[Image:74.jpg|none|thumb|500px|The estimated probability distribution for 15-PGDH 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.  ]]
 +
 +
===k<sub>cat</sub>===
 
{|class="wikitable sortable"  
 
{|class="wikitable sortable"  
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|+  style="text-align: left;" | Enzyme Turnover Numbers
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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"
 +
|+  style="text-align: left;" | Description of the 15-PGDH kcat distribution
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! Mode (min-1) !! Confidence Interval  !! Location parameter (μ) !! Scale parameter (σ)
 +
|-
 +
| 8.12E+02 || 5.38E+00 || 7.19E+00 || 7.01E-01
 +
|}
 +
 +
[[Image:75.jpg|none|thumb|500px|The estimated probability distribution for 15-PGDH 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.  ]]
 +
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===Enzyme concentration ===
 
{|class="wikitable sortable"  
 
{|class="wikitable sortable"  
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|+  style="text-align: left;" | 15-PGDH 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"
 +
|+  style="text-align: left;" | Description of the 15-PGDH concentration distribution
 +
! Mode (mM) !! Confidence Interval  !! Location parameter (μ) !! Scale parameter (σ)
 +
|-
 +
| 1.12E+01 || 2.32E+00 || 2.87E+00 || 6.80E-01
 +
|}
 +
 +
[[Image:152.jpg|none|thumb|500px|The estimated probability distribution for 15-PGDH 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.  ]]
 +
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===K<sub>eq</sub>===
 
{|class="wikitable sortable"  
 
{|class="wikitable sortable"  
 
|+  style="text-align: left;" | Gibbs Free Energy Change
 
|+  style="text-align: left;" | Gibbs Free Energy Change
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|<ref name="MetaCyc”>[http://metacyc.org/META/NEW-IMAGE?type=REACTION&object=ARACHIDONATE-12-LIPOXYGENASE-RXN 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]</ref>
 
|<ref name="MetaCyc”>[http://metacyc.org/META/NEW-IMAGE?type=REACTION&object=ARACHIDONATE-12-LIPOXYGENASE-RXN 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]</ref>
 
|}
 
|}
 +
 +
{| class="wikitable"
 +
|+  style="text-align: left;" | Description of the 15-PGDH Keq distribution
 +
! Mode  !! Confidence Interval  !! Location parameter (μ) !! Scale parameter (σ)
 +
|-
 +
| 2.21E+00 || 1.00E+01 || 1.58E+00 || 8.91E-01
 +
|}
 +
 +
[[Image:76.jpg|none|thumb|500px|The estimated probability distribution for 15-PGDH 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.  ]]
  
 
== References ==
 
== References ==
 
<references/>
 
<references/>

Revision as of 13:57, 16 May 2019

Return to overview

15-hydroxyprostaglandin dehydrogenase, also known as (15-PGDH) metabolises PG into the 15-Keto variant via the oxidation of 15(S)-hydroxyl group. The enzyme is constituently expressed in the skin (Finhelm1982) and within the eicosanoid network it is reported as metabolising PGE2 and PGF2a.

It should be noted that Judson et al found that 15-PGDH expression of the enzyme decreases in response to UVR (Judson2010).


Reaction

Catalysed by 15-PGDH

Chemical equation

PGE2 \rightleftharpoons 15-Keto-PGE2

Rate equation

R66.PNG

Enzyme Parameters

Kms

Literature values
Value Units Species Notes Reference
0.008 mM Rat Skin Method:

pH:7.4 Temperature: 37'C Substrate: PGE2 + NAD+

[1]
0.0075 mM Rat Skin Method:

pH:7.4 Temperature: 37'C Substrate: PGE2 + NADP+

[1]
0.024 mM Rat Skin Method:

pH:7.4 Temperature: 37'C Substrate: PGF2a + NAD+

[1]
0.023 mM Rat Skin Method:

pH:7.4 Temperature: 37'C Substrate: PGF2a + NADP+

[1]
0.0039 mM Purified Human 15-PGDH Method: In vitro

Expression Vector: E. coli pH:7.5 Temperature: 37'C Substrate: PGE2

[2]
0.0099 mM Purified Rat 15-PGDH Method: In vitro

Expression Vector: E. coli pH:7.5 Temperature: 37'C Substrate: PGE2

[2]
0.0055 ± 0.0006 mM Human Method:In vitro

Expression Vector: E. Coli pH:8 Temperature: 25 Substrate: PGE2 + NAD+

[3]
Description of the 15-PGDH Kms distribution
Mode (mM) Confidence Interval Location parameter (μ) Scale parameter (σ)
7.64E-03 5.05E+00 -4.41E+00 6.80E-01
The estimated probability distribution for 15-PGDH 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

Description of the 15-PGDH Kmp distribution
Mode (mM) Location parameter (μ) Scale parameter (σ)
7.70E-03 -4.41E+00 6.72E-01
The estimated probability distribution for 15-PGDH 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 Reference
816 ± 18 per minute Human Method: In vitro

Expression Vector: E. Coli pH:8 Temperature: 25 Substrate: PGE2 + NAD+

[3]
366 ± 12 - 846 ± 12 per minute Human Method: In vitro

Expression Vector: E. Coli pH:8 Temperature: 25 Substrate: PGE2 + NAD+ + Inhibitor

[3]
Description of the 15-PGDH kcat distribution
Mode (min-1) Confidence Interval Location parameter (μ) Scale parameter (σ)
8.12E+02 5.38E+00 7.19E+00 7.01E-01
The estimated probability distribution for 15-PGDH 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.

Enzyme concentration

Literature values
Value Units Species Notes Reference
69.8 ppm Human Expression Vector: Esophagus

Enzyme: 15-PGDH pH: 7.5 Temperature: 37 °C

[4]
22.1 ppm Human Expression Vector: Heart

Enzyme: 15-PGDH pH: 7.5 Temperature: 37 °C

[5]
11.2 ppm Human Expression Vector: Esophagus

Enzyme: 15-PGDH pH: 7.5 Temperature: 37 °C

[5]
7.68 ppm Human Expression Vector: Skin

Enzyme: 15-PGDH pH: 7.5 Temperature: 37 °C

Paxdb - Unknown
Description of the 15-PGDH concentration distribution
Mode (mM) Confidence Interval Location parameter (μ) Scale parameter (σ)
1.12E+01 2.32E+00 2.87E+00 6.80E-01
The estimated probability distribution for 15-PGDH 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.

Keq

Gibbs Free Energy Change
Value Units Species Notes Reference
(-0.46818542) kcal/mol Calculated Estimated

Enzyme: 15-PGDH Substrate: PGE2 Product: 15-dehydro-PGE2 pH: 7.3 ionic strength: 0.25

[6]
Description of the 15-PGDH Keq distribution
Mode Confidence Interval Location parameter (μ) Scale parameter (σ)
2.21E+00 1.00E+01 1.58E+00 8.91E-01
The estimated probability distribution for 15-PGDH 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.

References

  1. ↑ 1.0 1.1 1.2 1.3 N. Fincham, Novel prostaglandin dehydrogenase in rat skin. Biochem J. 1983 Apr 15;212(1):129-34.
  2. ↑ 2.0 2.1 Zhou H., C-Terminal region of human NAD+-dependent 15-hydroxyprostaglandin dehydrogenase is involved in the interaction with prostaglandin substrates. Eur J Biochem. 2001 Jun;268(12):3368-74.
  3. ↑ 3.0 3.1 3.2 F. Niesen,, High-Affinity Inhibitors of Human NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase: Mechanisms of Inhibition and Structure-Activity Relationships PLoS One. 2010 Nov 2;5(11):e13719.
  4. ↑ M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587
  5. ↑ 5.0 5.1 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
  6. ↑ 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
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