Download - Gluconeogenesis
Gluconeogenesis
Formation of glucose from non-carbohydrate source
• occurs mainly in liver and
• to a limited extent in kidney & small intestine
• Synthesis of glucose from pyruvate utilizes many of the same enzymes as Glycolysis
• Three Glycolysis reactions have such a large negative G that they are essentially irreversible Hexokinase (or Glucokinase) Phosphofructokinase Pyruvate Kinase
These steps must be bypassed in Gluconeogenesis.
The first two of the bypass reactions involve simple hydrolysis reactions
Glucose-6-Phosphatase (Gluconeogenesis) catalyzes:
glucose-6-phosphate + H2O glucose + Pi
This enzyme is embedded in the endoplasmic reticulum (ER) membrane in liver cells
H O
OH
H
OHH
OH
CH2OH
H
OH
HH O
OH
H
OHH
OH
CH2OPO32
H
OH
HH2O
1
6
5
4
3 2
+ Pi
glucose-6-phosphate glucose
Glucose-6-phosphatase
Fructose-1,6-bisphosphatase (Gluconeogenesis) catalyzes:
fructose-1,6-bisP + H2O fructose-6-P + Pi
fructose-6-phosphate fructose-1,6-bisphosphate
Phosphofructokinase CH2OPO3
2
OH
CH2OH
H
OH H
H HO
O6
5
4 3
2
1 CH2OPO32
OH
CH2OPO32
H
OH H
H HO
O6
5
4 3
2
1ATP ADP
Pi H2O
Fructose-1,6-biosphosphatase Fructose-1,6-bisphosphatase
Bypass of Pyruvate Kinase:
Pyruvate Kinase (last step of Glycolysis) catalyzes: phosphoenolpyruvate + ADP pyruvate + ATP
For bypass of the Pyruvate Kinase reaction, 2 ~P bonds is required.
Bypass of Pyruvate Kinase (2 enzymes):
Pyruvate Carboxylase (Gluconeogenesis) catalyzes:pyruvate + HCO3
+ ATP oxaloacetate + ADP + Pi
PEP Carboxykinase (Gluconeogenesis) catalyzes:oxaloacetate + GTP PEP + GDP + CO2
C
C
CH 2
O O
O PO 32
C
C
CH 3
O O
O
A T P A D P + P i C
CH 2
C
C
O
O O
O O
HC O 3
G T P G D P
CO 2
p y r u v a te o x a lo a c e ta te P E P
P y ru v a te C a rb o x y la s e P E P C a rb o x y k in a s e