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Lehninger
Principles of
Biochemistry
5th edition

Nelson & Cox

http://www.genome.ad.jp/kegg/pathway/map/map01100.html
c
 
  

 Cells dynamic    .

 egulatory mechanism evolved under strong

__________ pressure.

 c
  respond to changes in

_____________ concentration.


nzyme can be  in several ways.

Π


  
 

       

 _______ a phosphoryl group

from £
to a  , , or
 residue in an enzyme or
other protein substrate.

 Protein phosphatases
__________ the phosphoryl
group as Pi.
c 
£
     £
 
 
   
c
 
 
c
 
  
 

 Catalyzes  of


into Glycolysis

  enzyme

    (I-IV)
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  (muscle cell)
  

 for glucose

(half saturated at !")
 Glucose entering myocyte has a concentration
of 
-    to work at 
 .

 uscle    and  are     by

higher levels of their product
   .

Isozymes are temporarily and reversibly inhibited to keep a

balance with utilization.
£   


http://bio.winona.edu/berg/ANINS/allostan.gif
c
 
 
  #  
  isozyme: Its different

1. Its `
÷

 reaches

at m of Glucose.
(above normal blood glucose level)

xcess glucose (after meal) is

transported to ___________ where
  # converts it into
Glucose 6-phosphate.

$. Specifically  by a binding of a


   in liver.
c
 
     #

 ighter 
by regulatory protein in  

of Π
  

 hile  levels of


relieves this binding/ inhibition.

 Low blood glucose level (<%) (Fasting),

Fructose 6-P triggers inhibition of _____________
via binding of the 
  .

&  that liver    with other

organs for the glucose.
c
 
   Hexokinase IV

egulatory Protein
 Hexokinase
IV insidenucleus
_________,
away from cytosolic
enzymes of
.
glycolysis
Higher glucose levels in cell leads to higher level in nucleus and
results into release Hexokinase IV from regulatory protein
allowing it to enter cytosol.

Hexokinase IV is not  by the higher levels of

Glucose 6-Phosphate and continue to operate while Hexokinase I-III
are inhibited.
c
 
  

Π" Allosterically regulated
  binds
Œ" at an allosteric site & inhibits it
by ' 
its affinity for Fructose 6-Phosphate.

 hile £
& £
 this inhibition by AP.

c
 
 
› 

 

- Higher conc. of  enhances inhibition by AP.

(ells system that glucose need not to be utilized for AP generation)

- Π$(    is allosteric _________

of PFK-1.

(©


 
` )
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c
 
  

 

-     all  by high concentrations of

- AP, Acetyl-CoA and long-chain fatty acids.

- Liver () form of PK: regulated by  .

c
 
 
 
- Several steps are __________.

- £ £ _____ the formation

of oxaloacetate.

- Inhibits pyruvate dehydrogenase

complex.

c
 
 
 

- FBPase-1 is inhibited strongly by _______

- while the _______ is activated.

Coordinated regulation of both pathways in

a reciprocal manner.
 
 
c
 
 
 

 Besides these allosteric regulation inside cell.

 here could also be  regulation

from ___________ of cell:

Insulin (51 aa),

glucagon (29 aa) etc.
Fructose 2,6-bisphosphate mediated regulation

Both   and

 
 

-? levels of 
 in the events of lower blood glucose levels

signals   to:
-  and    more glucose and
-  using it.

his is mediated by Π$(    which is

______________regulator of :
Œ" and Œ
 "
Fructose 2,6-bisphosphate mediated regulation

 ithout Fructose 2,6BP binding PFK-1 is virtually .

 Its binding stimulates
  and at the same time

_______ FBPase-1 to slow down
 
  
Fructose 2,6-bisphosphate mediated regulation
he cellular levels of F2,6-BP reflects levels of  in
the blood:
-Glucagon ? with in ________ level.

Œ$( 
levels: Controlled by its

 and  '.

Œ$( 
formed by phosphorylation of Fructose 6-P, catalyzed by

 and broken by Œ
 $
(both are different from PFK-1 & FBPase-1)
Fructose 2,6-bisphosphate mediated regulation

Œ$ and Œ
 $ are two distinct activities of the _______
bifunctional protein:
- regulated by  and .
Fructose 2,6-bisphosphate mediated regulation
  increases the F2,6-BP levels:
- 
glycolysis and  gluconeogenesis.


 lowers the F2,6-BP levels:

-  glycolysis and 
gluconeogenesis.