Transcript Transition State of a Creatine Molecule during Dehydration

Transition State of a Creatine
Molecule during Dehydration
Computation Chemistry Seminar 2000
Ravi Agarwal
John O’Dowd
Purpose
 The purpose of our project was to determine
the transition state of the dehydration of
creatine into creatinine. This reaction was
chosen because of our interest in creatine as
a body supplement in the body.
Background Information
 Creatine is an amino acid (a protein) that is
produced in tiny doses by the liver, kidneys and
pancreas and stored in the muscles. In food, it is
found in meat and fish.
 Creatine is the guanidine- derived, phosphorylated
compound which maintains cellular ATP
homeostasis in the higher animals.
 Creatine is also a body supplement used to increase
anaerobic performance.
Background Information
 Creatine helps the body replenish energy through
the reaction of creatine monohydrate to creatine
phosphate.
 Energy in the muscles comes from the reaction of
adenosine triphosphate to adenosine diphosphate
(ATP ADP). Creatine helps replenish energy by
donating its phosphate back to ADP so the process
can repeat.
Background Information
 Creatinine is the dehydrated form of creatine.
Its significance bio-chemically is that
creatine cannot be excreted from the body.
So the body dehydrates it and then excretes
creatinine.
Dehydration of Creatine
NH2
NH
C
C
CH3
NH
N
O
CH3
NH
N
CH2
C
OH
CH2
+ H20
C--O
Computation Approach
 The experiment began with the use of MacSpartan
on a Power Macintosh. We completed our project
using MacSpartan Pro.
 The transition state was determined using the SemiEmpirical method of AM-1.
 Due to the complexity of our molecule, the ab initio
method (321G*) was impractical. We used the
Semi Empirical method (AM-1) for all of
calculations.
Computation Approach
 First we built the creatine molecule in
MacSpartan Pro. Then we ran a geometry
optimization using the AM-1 basis set.
Using our predictions, we used the transition
search by editing the bonds so that the
creatinine is formed.
Transition Search Approach
The nitrogen
bonds to the
carbonyl.
The –OH group
bonded to the
carbon will attack
the hydrogen
bonded to the NH2
Computational Approach
 Then we ran a transition search for our prediction.
 In order to determine if the molecule was a true
transition state it must have one unique imaginary
frequency.
 After the frequency scan, our transition search was
determined to be a true transition state for the
dehydration of creatine.
 This molecule is the transition state.
Transition State
Moving
hydrogen
Nitrogen bonded
to carbonyl.
Transition State
 Has one imaginary frequency.
 Follows our prediction:


Nitrogen bonded to carbonyl
Hydrogen on the amine moves from to the
hydroxyl to form water.
Calculated single point energies to determine
activation energy using AM-1 basis set.
Optimized Transition State
 Transition State was optimized
using AM-1 basis set.
Single Point Energies
7.618
kcal/mol
20
10
0
-10 0
5.287 kcal/mol
Transition
2
Creatinine
4
6
8
-20
-30
Activation
Energy:
-40
-50
-60
-70
Creatine
-62.958 kcal/mol
70.576 kcal/mol
Conclusion
 Found transition state for dehydration of
creatine based on one imaginary frequency
when we scanned the transition structure.
 Calculated Single Point Energies to
determine activation energy. Activation
energy is large so an enzyme most likely
catalyzes the reaction.