ATCase Flashcards
ATCase catalyses
first step of biosynthesis of pyrimidines
ATCase does not follow
M-M kinetics
allosterically inactivated by
CTP
allosterically activated by
ATP
CTP
pyrimidine nucleotides
ATP
purine nucleotides
CTP and ATP are like
competitive inhibiter–> increase Km but do not affect Vmax
allosteric effectors that show a sigmoidal graph are referred to as
K system effectors
to make nucleic acid pyrimidine and purines have to be
in equal amounts
too much ATP
ATCase is activated to synthesise pyrimidine nucleotides until conc of ATP and CTP become balanced
too much CTP
ATCase is inhibited by CTP, therefor permits purine nucleotide biosynthesis to balance ATP and CTP
structure of ATCase
300KDa
C6R6
x2 C3 trimers
x3 R2 dimers
r
regulatory subunit
C
catalytic subunit
competitive inhibiter of ATCase
PALA
crystal structure in the presence of
PALA
PALA and ATCase
causes changes to the quaternary strucure
ATCase has 2 distinct forms
T state- tense
R state -relaxed
T state
tense
-CTP is binded and therefore not active
R state
relaxed
-ATP is binded and therefore active
CTP stabilises
T state
ATP stabilised
R state
shape of graph
sigmoidal instead of hyperbolic due to co-opertivity
co-opertivity
binding of the substrate to one Active site favours the conversion of the entire enzyme into the R state 000> increasing activity at other active sites
positive coop
binding of substrate to one subunit increases the likelihood of other subunits binding
negative coop
rare, but when binding to one subunit reduces the likelihood of the substrate binding
two models of Coopertivity
Concerted
Sequential
Sequential model discovered by
Koshland , Nemethy and Elmer
The sequential model
binding of the substrate to one subunit moves the subunit to the relaxed state
-makes it more likely neighbouring subunits will bind to the neighbouring subunits
The concerted model was discover by
Monod, Wyman and Chnageux
the concerted model
entire enzyme will switch from T state to R state in one go
- likelihood of this is determined by the number of substrate molecules bound
- after the switch binding of further substrate is more likely
which model is more acceptedL
concerted model since it explains enzyme behaviour better
