Math 183. Shtylla Assignment #1 Due on Wednesday, January 29, 2014 Name: Melissa M.

Hernandez

Spring 2014

Instructions: Solutions must be written clearly and stapled to this problem sheet. Scores will depend not only on being able to provide the correct answer, but also on your ability to present your thoughts in an organized and clear way. Any outside sources must be cited and also anyone you worked on this set with must be acknowledged. Read Section 1.2, Biochemical Kinetics in the class lecture notes.

1. Enzyme Kinetics. The reaction scheme shown below is central to the study of enzyme -mediated reactions in biochemistry. The reaction scheme is k1 k2 E+P. (1) C k1 E is the concentration of an enzyme that catalyzes the transformation of the substrate of the reaction (S) into the product (P). An enzyme-substrate complex (C), where the enzyme and complex are bound together. E+S a) Based on the law of mass action and examples in Chapter 1, write a differential equation system corresponding to the scheme. Solution: dS = k1 ES + k1 C dt dE = k1 ES + (k1 + k2 )C dt dC = k1 ES (k1 + k2 )C dt dP = k2 C dt b) From the dierential equation system verify that the following conservation statements hold: E (t) + C (t) = E0 S (t) + C (t) + P (t) = S0 (2) (3)

Interpret the conservation statements in terms of the amount of the reactants and enzyme. Solution:

Math 183. Shtylla

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dC dE + = k1 ES k1 C k2 C k1 ES + k1 C + k2 C = 0 dt dt 0= dC dE + dt dt

E0 = C (t) + E (t) dS dC dP + + = k1 ES + k1 C + k1 ES k1 C k2 C + k2 C = 0 dt dt dt dS dC dP 0= + + dt dt dt S0 = S (t) + C (t) + P (t) c) Use the conservation relation E = E0 C to obtain a system of two dierential equations for S and C. Solution: dS = k1 E0 S + (k1 S + k1 )C, dt dC = k1 E0 S (k1 S + k1 + k2 )C. dt d) It is often the case that the enzyme-substrate complexes form rapidly, and that the enzymes are then working at full capacity. Thus, we assume dC/dt 0, which is referred to as quasi steady state approximation. Using +k2 show that this assumption and using Km = k1 k1 dP dS Vmax S = = = V, dt dt Km + S Vmax = k2 E0 . (4)

The equation above is known as the Michaelis-Menten kinetics. It is an approximation for the rate at which substrate is used up and product is formed, which is seen to dependent on substrate concentration. V is dened as the reaction velocity and it is a saturating function of S. Solution: dP dS = dt dt dS = (k1 E0 S + k1 SC + k1 C ) dt dS = k1 E0 S k1 SC k1 C dt

Math 183. Shtylla

Spring 2014

dS dC = k1 E0 S k1 SC k1 C k1 E0 S + k1 SC + k1 C + k2 C dt dt dP = k2 C dt
dC dt

We then solve for C in

= 0. C= k1 E0 S S + k1 + k2

We then plug our C into k2 C, and get: dP k1 k2 E0 S Vmax S = = = V. dt S + k1 + k2 Km + S Therefore, dP = V. dt 2. Simulation study. Consider the two species chemical kinetic scheme we discussed in the notes: k1 A+B (5) P. k1 a) Write down a dierential equation model that describes the chemical reaction given. Solution: dA = k1 AB + k1 P dt dP = k1 AB k1 P dt b) Suppose A, B, P are all measured in the same concentration units (for example in M) and time is measured in seconds. What are the units of k1 , k1 ? Solution: k1 = 1 1 = (time)(concentration) (seconds)(M ) k1 = 1 1 = time seconds

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c) Adapt the Matlab code given in the notes to simulate this model by changing the equations appropriately. Solution:
1 2 3 4 5 6 7 8 9 10 11 12 13 14

function p o l y m e r k i n e t i c s %Model paramters t i n i t =0; t f i n a l =10; k1=1 k2 =0.1 a0 =1; % mumM P0=0; % mumM

%S o l v e t h e ode u s i n g t h e ode45 b u i l t i n Matlab s o l v e r ; n o t i c e the placement 15 %o f t h e i n i t i a l c o n d i t i o n s and t h e f u n c t i o n h a n d l e that c a l l s the rig ht 16 %hand s i d e o f t h e system o f odes . [ T,Y] = ode45 ( @polymer ode , [ t i n i t t f i n a l ] , [ a0 P0 ] ) ;

17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

function dy=polymer ode ( t , y ) %This f u n c t i o n i s c r e a t e d t o d e f i n e t h e r i g h t hand s i d e o f t h e ode %system , and i t i s used w i t h @ t o f e e d as a function handle into %t h e s o l v e r ode45 . dy = zeros ( 2 , 1 ) ; %S e t up t h e r i g h t hand s i d e o f t h e ode %RHS o f ode dy ( 1 ) = k1 y ( 1 ) y ( 1 )+k2 y ( 2 ) ; dy ( 2 ) = k2 y ( 2 )+k1 y ( 1 ) y ( 1 ) ;

Math 183. Shtylla

32 33 34 35 36 37 38 39

Spring 2014

end %P l o t t h e r e s u l t s o f t h e n u m e r i c a l i n t e g r a t i o n o f ode45

plot (T,Y( : , 1 ) , b ,T,Y( : , 2 ) , o r ) xlabel ( time , F o n t S i z e , 1 2 )%i n s e r t t h e x l a b e l t e x t ylabel ( c o n c e n t r a t i o n s , F o n t s i z e , 1 2 )%i n s e r t t h e y label text 40 axis ( [ 0 5 0 1 ] ) % S e t t h e a x i s l i m i t s u s i n g a x i s ( [ xmin xmax ymin ymax ] ) 41 h l e g=legend ( A , P )%i n s e r t t h e l e g e n d 42 set ( h l e g , F o n t s i z e , 1 4 )
43 44

end

d) Suppose that initially there is no product, only reactants, so that A(0) = B (0) = 1, P (0) = 0. Explore solutions to this model in Matlab in the following cases: (i)k1 = 1, k1 = 0.1, and (ii) k1 = 1, k1 = 1. Solution:

Math 183. Shtylla

Spring 2014

1 0.9 0.8 0.7

A P

concentrations

0.6 0.5 0.4 0.3 0.2 0.1 0

0.5

1.5

2.5

3.5

4.5

time

Student Version of MATLAB

Figure 1: k1 = 1 and k1 = 0.1.

Math 183. Shtylla

Spring 2014

1 0.9 0.8 0.7

A P

concentrations

0.6 0.5 0.4 0.3 0.2 0.1 0

0.5

1.5

2.5

3.5

4.5

time

Student Version of MATLAB

Figure 2: k1 = 1 and k1 = 1