Transformation of PGH2 to PGD2

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The isomerisation of PGH2 to PGD2 is performed by PGDS to yield 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 which does not require glutathione for catalysis and H-PGDS, the hemopoietic type which does require glutathione. L-PGDSG is typically found in the brain, heart and testis, whereas H-PGDS is primarily found in the cytoplasm (Zhou2010 ref 6 and 7).

Upon binding to the D prostanoid (DP) receptor, the prostanoid stimulates keratinocyte cells to produce peptides which target invading pathogens (Homey, Steinhoff et al. 2006). However this species is primarily produced by LCs, mast cells and melanocytes in the cutaneous compartment (Ujihara, Horiguchi et al. 1988, Shimura, Satoh et al. 2010), and as a consequence it is unlikely to be observed in the early experimental procedures of this project.

Reaction

R21 PGH2 - PGD2.jpg

Chemical equation

PGH2 \rightleftharpoons PGD2

Rate equation

R21.PNG

Enzyme Parameters

Kms

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

Enzyme: PGDS pH: 8 Temperature: 25

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

Enzyme: PGDS pH:10 Temperature: Unspecified

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

Enzyme: PGDS pH:6.5 Temperature: Unspecified

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

Enzyme: PGDS pH:7 Temperature: 25

[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 Reference
158.4 per minute Human Expression Vector: Human Cell

Enzyme: PGDS pH: 8 Temperature: 25

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

Enzyme: PGDS pH:6.5 Temperature: Unspecified

[3]
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

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

Enzyme: PGDS pH: 7.5 Temperature: 37 °C

[6]
101 ppm Human Expression Vector: Oral Cavity

Enzyme: PGDS pH: 7.5 Temperature: 37 °C

[7]
67.9 ppm Human Expression Vector: Esophagus

Enzyme: PGDS pH: 7.5 Temperature: 37 °C

[6]
44.5 ppm Human Expression Vector:Skin

Enzyme: PGDS pH: 7.5 Temperature: 37 °C

[7]
Description of the PGDS concentration distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
6.76E+01 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 Reference
caption kJ/mol Human Expression Vector: E. Coli

Enzyme: L-PGDS pH: 8 Temperature: 25

[8]
5.72 kcal/mol Not stated Estimated

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

[9]
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. ↑ [http://www.ncbi.nlm.nih.gov/pubmed/8093029 Watanabe K. , "Identification of beta-trace as prostaglandin D synthase. Biochem Biophys Res Commun. 1994 Sep 15;203(2):1110-6. ]
  3. ↑ 3.0 3.1 [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. ]
  4. ↑ [https://www.ncbi.nlm.nih.gov/pubmed/3930495 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. ↑ 6.0 6.1 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
  7. ↑ 7.0 7.1 M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587
  8. ↑ [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]
  9. ↑ 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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