Gluconeogenesis
Definition : Non Carbohydrate  Glucose
 Site
: Liver (80%), Kidney 20%)
? Small Intestine
Why Glucose is very important!
• Brain always requires glucose
• In muscle as substrate for ATP production without
oxygen
• Erythrocyte use only glucose for energy production
• Mammary gland  lactose
Gluconeogenesis : For lactate clearance
In Ruminant propionic acid is substrate for
gluconeogenesis





Lactic Acid  Glucose
The path : TCA Cycle and reversal of glycolysis
with four additional enzymes:
Pyruvate Carboxylase
PEP Carboxykinase
F 1,6 BPase
G 6Pase
Glycerol  Glucose
Glycerol from lipolysis ( break down of Triglyceride)
taken up by the liver
Glycogenic amino acids

glucose
PEP
O
O
O

-O
C
C
C
C
O
CH3
ATP
pyruvate
HCO3-
Mg++
O
O
O
N
NH
carboxybiotin
CH CH
H 2C
S

O
CH
(C H 2 ) 4
C
NH
R
O
C
C
ADP
C
O
HN
NH
biotin
+
CH CH
CH2
Pi
H 2C
C
O
O

oxaloacetate
CH
S
(C H 2 ) 4
O
C
NH
R
PEP Carboxykinase

Human, cow and guinea pig, in the
mitochondria
and in the cytoplasm
 In rats only in the mitochondrions
 In birds and marmots only in the
mitochondrion
Malate and PEP in human exit from the
mitochondrion
In rats malate transported out of the
mitochondrion and converted to oxaloacetate
Gluconeogenesis and Glycolysis are reciprocally regulated
• Fructose 1,6-bisphosphatase is main regulatory step in gluconeogenesis.
• Corresponding step in glycolysis is 6-phosphofructo-1-kinase (PFK-1).
• These two enzymes are regulated in a reciprocal manner by several
metabolites.
Fructose-6-phosphate
+ Citrate
Citrate AMP +
F 2,6-BP +
6-phosphofructo
-1-kinase
Fructose
1,6-bisphosphatase
- AMP
- F 2,6-BP
Fructose 1,6-bisphosphate
Reciprocal control—prevents simultaneous reactions in same cell.
Propionate

Glucose
Ala
Cys
Gly
Ser
Thr
Trp
Fates of Amino Acid
degradation products
Glucose
Pyruvate
Phosphoenolpyruvate
Asn
Asp
Leu
Lys
Ile
Acetyl CoA
Acetoacetate
Phe
Trp
Tyr
Citrate
Oxaloacetate
Isocitrate
Citric
Acid
Cycle
Malate
Phe
Tyr
Gln
a-Ketoglutarate
Fumarate
Glucogenic
Ketogenic
Both Glucogenic & Ketogenic
Succinate
Succinyl CoA
Glu
Ile
Met
Thr
Val
Arg
His
Pro
Ala
Cys
Gly
Ser
Thr
Trp
Fates of Amino Acid
degradation products
Glucose
Pyruvate
Phosphoenolpyruvate
Asn
Asp
Leu
Lys
Ile
Acetyl CoA
Acetoacetate
Phe
Trp
Tyr
Citrate
Oxaloacetate
Isocitrate
Citric
Acid
Cycle
Malate
Phe
Tyr
Gln
a-Ketoglutarate
Fumarate
Glucogenic
Ketogenic
Both Glucogenic & Ketogenic
Succinate
Succinyl CoA
Glu
Ile
Met
Thr
Val
Arg
His
Pro