Geranyl diphosphate synthase (GPPS)

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You can go back to main page of the kinetic model here.

Model construction progress :

Enzyme Pathway Keq Kcat VmaxF KmIPP KmDMAPP [Sub1] [Sub2] VmaxR KmGPP KmPP [Prod1] [Prod2]
01_GPPS Limonene Biosynthesis 1 3 4 4 4 3 3


Legend:

Have not started ·· 1 -2 data found ·· 3-4 data found ·· sufficient data found/estimated ·· data distribution generated ·· data sampled
to do DONE!

What we know

Issues

Strategies

Reaction catalysed

dimethylallyl diphosphate + isopentenyl diphosphate \rightleftharpoons geranyl diphosphate + diphosphate
DMAPP + IPP \rightleftharpoons GPP + PP

Metabolite and Enzyme Background Information

Long metabolite names are abbreviated in the model for clarity and standard identification purposes.

Metabolite Abbreviation Chemical Formula Molar mass (g/mol) ChEBI ChEMBL PubChem MetaCyc BRENDA
dimethylallyl diphosphate DMAPP
isopentenyl diphosphate IPP
geranyl diphosphate GPP C10H20O7P2 314.209 17211 41432 445995
diphosphate PP O7P2 173.94 644102
geranyl diphosphate synthase GPPS 32.16 kD (from nucleotide sequence), 36 kD (experimental) CPLX-8656 2.5.1.1

Equation Rate

Failed to parse (Cannot store math image on filesystem.): V_\mathrm{GPPS} = Vmax_\mathrm{forward} * \cfrac { \left (\cfrac{[DMAPP]}{Km_\mathrm{DMAPP}} * \cfrac{[IPP]}{Km_\mathrm{IPP}}\right )* \left ( 1 - \cfrac {[GPP]*[PP]}{[GPP]*[PP]*K_\mathrm{eq}} \right )}{\left (1 + \cfrac {[IPP]}{Km_\mathrm{IPP}} + \cfrac {[PP]}{Km_\mathrm{PP}} \right ) * \left ( 1 + \cfrac {[DMAPP]}{Km_\mathrm{DMAPP}} + \cfrac {[GPP]}{Km_\mathrm{GPP}} \right )}


Parameter Description
VGPPS Reaction rate for Geranyl diphosphate synthase
Vmaxforward Maximum reaction rate towards the production of GPP
KmGPP Michaelis-Menten constant for GPP
KmIPP Michaelis-Menten constant for IPP
KmPP Michaelis-Menten constant for PP
KmDMAPP Michaelis-Menten constant for DMAPP
Keq Equilibrium constant
[GPP] GPP concentration
[DMAPP] DMAPP concentration
[IPP] DMAPP concentration
[PP] PP concentration

Strategies for estimating the kinetic parameter values

Calculating the Equilibrium Constant

Standard Gibbs Free energy for GPPS from MetaCyc is -13.0 kcal mol-1.

The equilibrium constant can be calculated using the Van't Hoff Isotherm equation:

K_\mathrm{eq} = exp \left ( \cfrac {-∆G^{°'}}{RT} \right )


Failed to parse (Cannot store math image on filesystem.): = exp \left ( \cfrac {-(-13.0 \text { kcalmol}^{-1})}{ (1.98722 \text{ calK}^{-1} \text { mol}^{-1} * 289 K} \right )

Failed to parse (Cannot store math image on filesystem.): = exp \left ( \cfrac {13.0 \text { kcalmol}^{-1} }{ 574.30658 \text{ calK}^{-1}\text { mol}^{-1} }\right)

Failed to parse (Cannot store math image on filesystem.): = exp \left ( \cfrac{ 13000 \text {calmol}^{-1}}{574.30658 \text{ cal}\text { mol}^{-1}} \right)


Failed to parse (Cannot store math image on filesystem.): = 6788526395


where;

Keq Equilibrium constant
-?G° Gibbs free energy change. For GPPS it is -13.0 kcalmol-1
R Gas constant with a value of 1.98722 calK-1mol-1
T Temperature which is always expressed in kelvin, as a standard, I used 298 K

Published Kinetic Parameter Values

Values for the kinetic parameter required to simulate this model can be obtained from published and unpublished literature.

A more detailed descriptions of the values listed above can be found HERE , where I've linked and highlighted where these data came from.

Substrate, Product & Enzyme Concentration Values

Concentration Unit Substrate / Product Directionality Organism References
15 µM IPP forward Phaedon cochleariae [1]
50 µM DMAPP forward Phaedon cochleariae [1]
50 µM DMAPP forward Phaedon cochleariae [1]
50 µM IPP forward Phaedon cochleariae [1]
250 µM IPP forward Picea abies [2]
800 µM DMAPP forward Picea abies [2]

Km Values

Km (mM) Unit Substrate / Product Directionality Organism References
81 μM DMAPP forward Mentha sp. [3]
88 μM IPP forward Mentha sp. [3]
241 μM DMAPP forward Mentha sp. [3]
215 μM DMAPP forward Mentha sp. [3]
44 μM IPP forward Abies grandis [4]
55 μM IPP forward Abies grandis [4]
44 μM IPP forward Abies grandis [4]
163 μM DMAPP forward Abies grandis [4]
90 μM DMAPP forward Abies grandis [4]
82 μM DMAPP forward Abies grandis [4]
0.84 μM IPP forward Phaedon cochleariae [1]
11.6 μM DMAPP forward Phaedon cochleariae [1]
1103 μM DMAPP forward Phaedon cochleariae [1]
11.79 μM IPP forward Phaedon cochleariae [1]
58 μM DMAPP forward Mycobacterium tuberculosis [5]
163 μM IPP forward Mycobacterium tuberculosis [5]
390 μM DMAPP forward Picea abies [2]
170 μM IPP forward Picea abies [2]

Vmax values

Vmax Unit Directionality Organism References
0.44 µmol/min/mg (unit) forward Phaedon cochleariae [1]
0.67 µmol/min/mg (unit) forward Phaedon cochleariae [1]
2.39 µmol/min/mg (unit) forward Phaedon cochleariae [1]
0.17 µmol/min/mg (unit) forward Phaedon cochleariae [1]
4.2 nkat/mg forward Picea abies [2]

Kcat values

Kcat Unit Organism Reference
0.7 min-1 Mycobacterium tuberculosis [5]
5.1 min-1 Mycobacterium tuberculosis [5]
1.4 s-1 Picea abies [2]
1.8 s-1 Abies grandis [4]
0.5 s-1 Abies grandis [4]
1.6 s-1 Abies grandis [4]

Extracting Information from (INSERT SUBSTRATE/PRODUCT) Production Rates

Amount produced (mg/L) Time (H) Organism Description Reaction Flux (µM/s)
X X Y Z Z
X X Y Z Z
X X Y Z Z
X X Y Z Z
X X Y Z Z
X X Y Z Z

Simulations

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Frick, S. 2013. "Metal ions control product specificity of isoprenyl diphosphate synthases in the insect terpenoid pathway", PNAS, 110(11):4194-4199 Cite error: Invalid <ref> tag; name "Frick2013" defined multiple times with different content Cite error: Invalid <ref> tag; name "Frick2013" defined multiple times with different content Cite error: Invalid <ref> tag; name "Frick2013" defined multiple times with different content Cite error: Invalid <ref> tag; name "Frick2013" defined multiple times with different content
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Schmidt, A. 2010. "A bifunctional geranyl and geranylgeranyl diphosphate synthase is involved in terpene oleoresin formation in Picea abies", Plant Physiology, 152:639-655
  3. ↑ 3.0 3.1 3.2 3.3 Burke, C. 2004. "Heteromeric geranyl diphosphate synthase from mint: construction of a functional fusion protein and inhibition by biphosphonate substrate analogs", Archives of Biochemistry and Biophysics, 422:52-60
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 Burke, C. 2002. "Geranyl diphosphate synthase from Abies grandis:cDNA isolation, functional expression, and characterization", Archives of Biochemistry and Biophysics, 405:130-136
  5. ↑ 5.0 5.1 5.2 5.3 Mann, F.M. 2011. "Rv0989c encodes a novel (E)-geranyl diphosphate synthase facilitating decaprenyl diphosphate biosynthesis in Mycobacterium tuberculosis", FEBS Letters, 585(3):549-554
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