Enzyme Kinetics and Metabolic Control Analysis
201
Figure 6.4 The slope of the lines on Fig. 6.3 as a function of inhibitor concentration.
6.2.2 Cooperativity and Allosteric Enzymes
We h a v e se e n a lre a d y in C h a p te r 2 th a t th e liv in g c ell is a b le to c o n tro l th e c o n c e n tra tio n o f
m etabolic in te rm e d ia te s in th e p a th w a y s w ith in n a rro w lim its. O n th e o th e r h a n d th e e n zy m atic
reaction in a p a th w a y sh o u ld b e a b le to re a c t q u ic k ly to a su d d e n e n v iro n m e n ta l c h a n g e in the
input o f su b stra te to th e p a th w a y . In p a rtic u la r th e ra te o f c o n v e rsio n o f th e su b stra te b y a
pathw ay e n z y m e sh o u ld b e se n sitiv e to c h a n g e s in th e su b stra te c o n c e n tra tio n a ro u n d the
“n o rm al” lev e l th at p re v a ils w h e n th e cell is o p e ra tin g at ste a d y state.
The d o w n w a rd s c o n v e x h y p e rb o lic sh a p e o f F ig . 6.1 sh o w s th at M ic h a e lis M e n te n k in etics is
unable to g iv e a h ig h se n sitiv ity o f
r
to c h a n g e s in
s
e x c e p t w h e n th e “ n o rm a l” su b stra te level is
close to zero . O n e m ig h t g u e ss th at th e sa tu ra tio n c o n sta n t
K
(o r A'„, in eq (6 .1 )) o f an e n zy m e in a
m icro o rg an ism h as b y e v o lu tio n se ttle d o n a v a lu e w h ic h w o u ld g iv e
r/rmm =
0.5 a ro u n d th e v-
value w h ic h is “ n o rm a lly ” o ffe re d to th e e n z y m e . I f su d d e n ly th e e n z y m e is e x p o se d to a p u lse o f
substrate 5 tim e s h ig h e r th an th e n o rm a l lev e l
s
=
K
th e n th e e n z y m e k in e tic s g iv e n by eq (6.1)
w ould o n ly in c re a se th e ra te o f th e re a c tio n fro m
r/rmM
= 0.5 to 5/6. It w o u ld tak e to o lo n g for the
enzym e to b rin g th e su b stra te lev e l b a c k to
s = K,
a n d in th e m e a n tim e o th e r p a th w a y re ac tio n s
may b e in h ib ite d (o r e v en re p re sse d ) b y th e h ig h lev e l o f su b stra te w a itin g to b e c o n su m e d b y the
enzym e.
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