Transformation of PGH2 to PGI2

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The isomerisation of PGH2 to prostacyclin (PGI2), is performed by prostaglandin I synthase (PGIS). This protein is a member of the CYP P450 family, but unlike most CYP P450 enzymes it does not oxidise PGH2. PGI2 is generated by the rearrangement of the peroxide functional group, whereby a hydroxyl group is formed at C11, and a new epoxide ring is formed between C9 and C6. PGI2 is generated by the sequential action of COX and PGIS, which co-localise in the ER, plasma membrane and nuclear membrane [1].

Reaction

R5 PGH2 - PGI2.jpg

Chemical equation

PGH2 \rightleftharpoons PGI2

Rate equation

R05.PNG

Parameters

Kms

Literature values
Value Units Species Notes Weight Reference
1.33E-02 ± 1.40E-03 mM Human Expression Vector: Bovine Endothelial and Aorta Cells

Enzyme: Human PGIS pH:7.4 Temperature: 23

256 [2]
9.00E-03 ± 5.00E-03 mM Bovine Expression Vector: Bovine Endothelial and Aorta Cells

Enzyme: Bovine PGIS pH:7.4 Temperature: 24

192 [3]
Description of the PGIS Kms distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.24E-02 2.46E+00 -4.22E+00 4.20E-01
The estimated probability distribution for PGIS 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 PGIS Kmp distribution
Mode (mM) Location parameter (µ) Scale parameter (σ)
1.29E-02 -4.182022605 0.414183521
The estimated probability distribution for PGIS 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
147 ± 45 per minute Cattle Expression Vector: E. Coli

Enzyme: Bovine PGIS pH:7.4 Temperature: 24

192 [4]
Description of the PGIS kcat distribution
Mode (min-1) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.41E+02 1.35E+00 5.028213628 0.287348692
The estimated probability distribution for PGIS 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

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

Literature values
Value Units Species Notes Weight Reference
412 ppm Human Expression Vector: Urinary bladder

Enzyme: PGIS pH: 7.5 Temperature: 37 °C

1024 [5]
206 ppm Human Expression Vector: Lung

Enzyme: PGIS pH: 7.5 Temperature: 37 °C

1024 [5]
60.1 ppm Human Expression Vector: Esophagus

Enzyme: PGIS pH: 7.5 Temperature: 37 °C

1024 [5]
9.93 ppm Human Expression Vector: Oral Cavity

Enzyme: PGIS pH: 7.5 Temperature: 37 °C

1024 [6]
Description of the PGIS concentration distribution
Mode (ppm) Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.13E+02 6.25E-04 4.13E+00 5.67E+00 9.68E-01
The estimated probability distribution for PGIS 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
0.04 kcal/mol Not stated Estimated

Enzyme: Transacylase Substrate: Product: pH: 7.3 ionic strength: 0.25

64 [7]
Description of the PGIS Keq distribution
Mode Confidence Interval Location parameter (µ) Scale parameter (σ)
9.35E-01 1.00E+01 7.30E-01 8.90E-01
The estimated probability distribution for PGIS 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.

References

  1. ↑ Smith, W. L. DeWitt, D. L. Allen, M. L. , Bimodal distribution of the prostaglandin I2 synthase antigen in smooth muscle cells, J Biol Chem (1983), 258, 5922-6.
  2. ↑ H. C. Yeh, P. Y. Hsu, Characterization of heme environment and mechanism of peroxide bond cleavage in human prostacyclin synthase. Biochim Biophys Acta. 2005 Dec 30;1738(1-3):121-32.
  3. ↑ Hara S., Isolation and molecular cloning of prostacyclin synthase from bovine endothelial cells. J Biol Chem. 1994 Aug 5;269(31):19897-903.
  4. ↑ [www.ncbi.nlm.nih.gov/pubmed/8051072 Hara S. , Isolation and molecular cloning of prostacyclin synthase from bovine endothelial cells. J Biol Chem. 1994 Aug 5;269(31):19897-903.]
  5. ↑ 5.0 5.1 5.2 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
  6. ↑ M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587
  7. ↑ 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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