Cita on:Mlmowsk

P,Carter TO,Weber OF(2013)Enzyme Cata ysis and he Outcome of 0 0Chem cal Rea ons U P,oteonics B:o nform 6i 432-

141 doi:10 417211pb 1000271

to allect outcome by turning periodic subslrate

inp!t into fl on-periodic

in the

prodr.rct generetion has been uncertain. Enamples were found

srbstrate
input

ES

EIP

r.
E+S ------!-

(xidase peroxidase reaction J6] and a hemin hydrogen peroddesuirtite model of.atal)$is [7], bul broad potential for non-linearity in
other emyme-calallzed systems has not been established. Enzlrnatic
reactions.an be described in general tenns by a set of ordinary
differential equatioDs for aII reactants (Figure 1). Thek format has some
resernblance to the differential equations descrihing the t,orellz and
Rdssler systems ofr}on-lillear dFami.s [8,9], and therelore implies the

k2

B
dE=(

?otential to generate cotupiex, possibly chaodc bchavior.

+k,)(IEtl lFl) kl:E]ISI k41E 111

dt

Here we test the h,lothesis that eru,)lnc calallsis can affcct the
outcome of biochemicxl reactions We investigate the panmeter
space for the rate aonstants in substrate-activated and general enzlme
catalysis, and we $tudy enzynre calalysis in a brarched reaction wirl
tr,o competing arms.

dES kl l ]lS + 4[E] P

Ot

= A Snd)

(k2+k3) ES

kl lLl

1+k2 EJ

dt

Materials and Methods

Ell k4:ElIP
dP k311
at

sirico modeling

'Ihe chemical reactioos under study can bc dcfined as sets of

ordioary dillerential equations (ODLS) thal describe t})e rate ofchange
of each reactant per time step- TIre soluiions oftllose equations show
constant, peaiodiq ol non-periodic flow over time- Here, a solver
ftom tr SciPy [t0] package (scipy.intcgrate.odeint) was used to model
en4ane catal)sis. To solve the equations under study, the time step was
sct to 0.01 seconds, resulting in a samp[ng frequency of 100 Hz. 'Ihe
inpui fluctuated at a constani rate of0.01 l{2, i.e. each oscil}atioo took
100 seconds or 10000 points. A double precision arilhmetic (64 bit)

EJ=lEl+

ESI

B ochen cal tat,on D

Figure l:GeneF l enZytt knetO equalo
ized se ofsubsmte
D,ffere l elualonS COmmontt k.-O h ihe sP

mnbnL_o The nrsttem m e l equalon tor

a mes rh/:hm c subslrde inp inihe rom oia sine wave

A
subirate

was applied

input

Non-lirar systcrns can be rcpresented in a hifurcation diagram

as a set of densely packed poirts- the use of a Fourier transform
Bives another method of visualization. lhe Fourier hansfbrm is
a sigral represe$ation in a liequency space. Wlrereas a siglal in
time domain shous how much energy is carried in a given time
period tLe Fourier spectrum shows how 1i!_h energy is carried in a
given frequency range. 'Ihe periodicity of a siglal is particularly well
represented on a Fourier spectrum-a-s a peak at a spediic frequency
(and at ha Donic frequencies). Because in the chaos regime every
period is presenl, the Irourier spectnfil of a chaotic signal has pealc
for every frequencp

L/
P

k5

t-he

sbw

I
k, 1+k21E l lEi4LSl)
dt
uES

q itcm is representcd by a recurrencq

oriy fixed

pofurts

not difierential, equation).

in sofle parameter rarge, this should

uS

[ 161)

(k4+kJ 161

lv+A notl

k,1111-:

If

dP

k`[61

i[.1 [ 1 lFSl

Foure 2:A)Poss' le rea on 3cheme for enzyme ca S ttth subslrate

advalon Vang et al t341) B,Set Of direren,al equations desc10ing lhe
reaon schett ofttbstrate ad" on(E= . E ES)The l lem hthe
reacton of substale cha"e assumes th/11m e substrate inplt n the brm ol

and the sualintlo

of rate tl

angts( atlVanted en e ttneu

PrOgram in Nellogo Model Llbrary httP

n. tlogO/1110dels

l)m ea rttctltln constant l hrougll i" a

stlbttaF volmle,ald the rate orthe lnupg lor mplilldc ad

For agent based modeling, a basic Netlrgo model on enzymc

kineli.s was cdiied to allow for contjnuous rh)4llmic substrate input

llequen")tO be set by the invc gator

nfom

74-276X P3 an open a m
`

cd nOrth estern edl1/

)nc PrOgram models ule rttral en nc tnCuc

reac o ( re

iSSN.0

lESl

dt

Agent-based modeling

J Ploleol cs B

}[ESl)S+

dt

be

rcprose[ted on the diagram a5 a solid [ine. Limit cycles are represented

as nrultiple, vertical lines. The number of lines depends on the peiiod
of oscillations. Chaos in this case is represented as a block of densely
packed points. lo define the reaction states of the enz)'rne catallsis, we
generxted bjfurcatioB maps by solving the sel of differential equations
(Figure 2) fbr each of its parameters At every ite.alion,local minima
and maxima qlues of a chosen variable v.ere plotted on a vertjcal a.xis.
Upon completion of lhe desired range o[ parameters, the resulting
graph presnts the change of the system's variables depending on the
delrcd parameter change.

k,([

1t

bilurcation djagram is a graphical method of presefltilrg a

change itl a dyiamical s]Btcm depending on a change in one of the
undcrlying parameters. A biiurcation plot represents a map, not a flow
a system has

fast

(the

suD rate cttnge

vdure

6(6) r32-!ar (2013)

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