CMK

The reaction

4-(cytidine 5′-diphospho)-2-C-methyl-D-erythritol kinase (CMK) catalyses the production of CDP-ME2P from CDP-ME. This ATP-dependent reaction is the fourth step in the non-mevalonate or methylerythritol-phosphate (MEP) pathway.

$CDPME + ATP \rightleftharpoons CDPME2P + ADP$

Equation Rate

CMK is modelled reversible using random bi-bi generic Michaelis-Menten equation

$V_\mathrm{CMK} = \cfrac{\left ( Kcat_\mathrm{forward} \cdot [CMK]\right ) \cdot \left (\cfrac{[CDP-ME]}{Km_\mathrm{CDP-ME}} \right ) \cdot \left(\cfrac{[ATP]}{Km_\mathrm{ATP}} \right) \cdot \left (1 - \cfrac{\cfrac{[CDP-ME2P]\cdot[ADP]}{[CDPME]\cdot[ATP]}}{K_\mathrm{eq}} \right)}{\left(1 + \cfrac{[CDP-ME]}{Km_\mathrm{CDP-ME}} + \cfrac{[ADP]}{Km_\mathrm{ADP}}\right)\cdot \left (1+ \cfrac{[ATP]}{Km_\mathrm{ATP}} +\cfrac{[CDP-ME2P]}{Km_\mathrm{CDP-ME2P}} \right)}$

where :

Parameter	Description	Units
VCMK	Reaction rate for CMK	μM/min
Kcatforward	Forward turnover number	min-1
KmCDPME	Michaelis-Menten constant for CDPME	μM
KmATP	Michaelis-Menten constant for ATP	μM
KmCDPME2P	Michaelis-Menten constant for CDPME2P	μM
KmADP	Michaelis-Menten constant for ADP	μM
Keq	Equilibrium constant	unitless
[CDPME]	CDPME concentration	μM
[ATP]	ATP concentration	μM
[CDPME2P]	CDPME2P concentration	μM
[ADP]	ADP concentration	μM

Parameters

To model CMK using the equation above, a total of 6 parameters are required. For each of this parameter, a lognormal distribution is generated using our PROMENADE pipeline. To include all uncertainties surrounding these parameters, generic parameter values are obtained from BRENDA and is also processed through PROMENADE.