Transformation of PGH2 to PGD2

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The isomerisation of PGH2 to PGD2 can be performed by prostaglandin D synthase (PGDS) and prostaglandin F synthase (PGFS). PGDS yields a hydroxyl group at C9 and a ketone group at C11. Two isoforms of PGDS have been found in humans, the lipocalin isoform, L-PGDS, does not require glutathione for catalysis whereas the hemopoietic type, H-PGDS, does require glutathione.

Reaction

R21 PGH2 - PGD2.jpg

Chemical equation

PGH2 \rightleftharpoons PGD2

Rate equation

R21.PNG

Enzyme Parameters

Kms

Literature values
Value Units Species Notes Weight Reference
0.0138 mM Human Expression Vector: Human Cell

Enzyme: PGDS pH: 8 Temperature: 25

512 [1]
4.00E-03 mM Human Expression Vector: Cerebrospinal Fluid

Enzyme: PGDS pH:10 Temperature: Unspecified

256 [2]
0.50 mM Human Expression Vector: E. Coli.

Enzyme: PGDS pH:6.5 Temperature: Unspecified

128 [3]
1.40E-02 mM Rat Expression Vector: Cerebrospinal Fluid

Enzyme: PGDS pH:7 Temperature: 25

256 [4]
Description of the PGDS Kms distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.35E-02 3.78E+00 -3.44E+00 9.29E-01
The estimated probability distribution for PGDS 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 PGDS Kmp distribution
Mode (mM) Location parameter (µ) Scale parameter (σ)
1.30E-02 -4.02E+00 5.69E-01
The estimated probability distribution for PGDS 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
158.4 per minute Human Expression Vector: Human Cell

Enzyme: PGDS pH: 8 Temperature: 25

256 [5]
1302 per minute Human Expression Vector: E. Coli.

Enzyme: PGDS pH:6.5 Temperature: Unspecified

128 [6]
Description of the PGDS kcat distribution
Mode (min-1) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.58E+02 1.50E+00 5.10E+00 2.00E-01
The estimated probability distribution for PGDS 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 concentrations

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

Literature values
Value Units Species Notes Weight Reference
156 ppm Human Expression Vector: Pancreas

Enzyme: PGDS pH: 7.5 Temperature: 37 °C

1024 [7]
101 ppm Human Expression Vector: Oral Cavity

Enzyme: PGDS pH: 7.5 Temperature: 37 °C

1024 [8]
67.9 ppm Human Expression Vector: Esophagus

Enzyme: PGDS pH: 7.5 Temperature: 37 °C

1024 [7]
44.5 ppm Human Expression Vector:Skin

Enzyme: PGDS pH: 7.5 Temperature: 37 °C

2048 [8]
Description of the PGDS concentration distribution
Mode (ppm) Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
6.76E+01 3.74E-04 1.64E+00 4.41E+00 4.49E-01
The estimated probability distribution for PGDS 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

Literature values
Gibbs Free Energy Change Units Species Notes Weight Reference
caption kJ/mol Human Expression Vector: E. Coli

Enzyme: L-PGDS pH: 8 Temperature: 25

64 [9]
5.72 kcal/mol Not stated Estimated

Enzyme: PGDS Substrate: Arachidonate Product: PGD2 pH: 7.3 ionic strength: 0.25

64 [10]
Description of the PGDS Keq distribution
Mode Confidence Interval Location parameter (µ) Scale parameter (σ)
7.46E+04 1.00E+01 1.20E+01 8.90E-01
The estimated probability distribution for PGDS 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. ↑ Zhou Y. , "Structure-function analysis of human l-prostaglandin D synthase bound with fatty acid molecules." FASEB J. 2010 Dec;24(12):4668-77. doi: 10.1096/fj.10-164863. Epub 2010 Jul 28.
  2. ↑ Watanabe K. , "Identification of beta-trace as prostaglandin D synthase."Biochem Biophys Res Commun. 1994 Sep 15;203(2):1110-6.
  3. ↑ Pinzar E , "Structural basis of hematopoietic prostaglandin D synthase activity elucidated by site-directed mutagenesis." J Biol Chem. 2000 Oct 6;275(40):31239-44.
  4. ↑ Urade Y. , "Purification and characterization of rat brain prostaglandin D synthetase." J Biol Chem. 1985 Oct 15;260(23):12410-5.
  5. ↑ Zhou Y. , "Structure-function analysis of human l-prostaglandin D synthase bound with fatty acid molecules. FASEB J. 2010 Dec;24(12):4668-77.
  6. ↑ [https://www.ncbi.nlm.nih.gov/pubmed/10871602 Pinzar E , "Structural basis of hematopoietic prostaglandin D synthase activity elucidated by site-directed mutagenesis. J Biol Chem. 2000 Oct 6;275(40):31239-44. ]
  7. ↑ 7.0 7.1 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
  8. ↑ 8.0 8.1 M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587
  9. ↑ [http://ac.els-cdn.com/S0014579314000982/1-s2.0-S0014579314000982-main.pdf?_tid=7f323a24-6543-11e6-82ac-00000aab0f01&acdnat=1471525305_289e200c1e492c5fa693179a5396fd82 Kume S., "Fine-tuned broad binding capability of human lipocalin-type prostaglandin D synthase for various small lipophilic ligands FEBS Letters Volume 588, Issue 6, 18 March 2014, Pages 962–969]
  10. ↑ 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

Related Reactions

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