GLUCONEOGENESIS

Biosynthesis of glucose
3 – 4 carbon noncarbohydrate precursors
Enzymes located in the cytosol
Gluconeogenic organs
Liver
Kidney cortex
Fates
Catabolism by nervous tissue
Utilization by skeletal muscles
 GLUCONEOGENESIS

SUBSTRATES
GLUCOGENIC AMINO ACIDS
LACTATE
GLYCEROL
PROPIONATE
 PRECURSORS
GLUCOSE

Fructose 1,6 - bisphosphate

PROPIONATE

Dihydroxyacetone Glyceraldehyde 3 - phosphate

phosphate

Glycerol 3 - phosphate Phosphoenolpyruvate SUCCINYL-

CoA

Oxaloacetate
GLYCEROL
Other
ALANINE PYRUVATE amino acids

LACTATE
 CORI CYCLE
SKELETAL MUSCLE BLOOD LIVER

GLUCOSE GLUCOSE

2ATP
6 ATP

2 PYRUVATE 2 PYRUVATE

2 LACTATE 2 LACTATE
 GLUCOSE

Fructose 1,6 - bisphosphate

LACTATE

Glyceraldehyde 3 - phosphate DHAP

PYRUVATE

1,3 Bisphosphoglycerate

PYRUVATE
3 - Phosphoglycerate

OAA OXALOACETATE
2 - Phosphoglycerate

PEP
Phosphoenolpyruvate
GLUCOSE - ALANINE CYCLE
SKELETAL MUSCLE BLOOD LIVER

GLUCOSE GLUCOSE

2ATP
6 ATP

2 PYRUVATE 2 PYRUVATE UREA

2NH2
2NH2

2 ALANINE 2 ALANINE
 GLUCOSE

ATP H2O 3
Glucose 6 - phosphate

Fructose 6 - phosphate
ATP H2O
2
Fructose 1,6 - bisphosphate
2NADH 2NADH

ATP 2ATP

Phosphoenolpyruvate

2GTP

2 Oxaloacetate 1
ATP
2ATP

2 PYRUVATE
 BYPASS REACTIONS
PYRUVATE to
PHOSPHOENOLPYRUVATE
PYRUVATE CARBOXYLASE
Generates OXALOACETATE
Mitochondrial matrix
ATP – Dependent
BIOTIN – dependent
ACETYL – CoA – positive allosteric activator
 BYPASS REACTIONS
PYRUVATE to PHOSPHOENOLPYRUVATE
PHOSPHOENOLPYRUVATE
CARBOXYKINASE
Decarboxylation and phosphorylation
Cytosol
Reversible
GTP – Dependent
PEP CARBOXYKINASE
PEP
O CO2
CARBOXYKINASE G

P P P
OC O
CCO O
CCH
O2
C2 O
CH
O
PHOSPHOENOLPYRUVATE
OXALOACETATE
 BYPASS REACTIONS

FRUCTOSE 1,6 – BISPHOSPHATE to

FRUCTOSE 6 - PHOSPHATE
FRUCTOSE 1,6 - BISPHOSPHATASE
LIVER
KIDNEY
SKELETAL MUSCLE
 BYPASS REACTIONS
GLUCOSE 6 – PHOSPHATE to GLUCOSE
GLUCOSE 6 - PHOSPHATASE
Irreversible
Hydrolysis
Endoplasmic reticulum of the liver
Absent in the brain and skeletal muscle
Requires Mg+
 SUMMARY of REACTIONS
REACTANTS
Pyruvate + CO2 + ATP +H2O
Oxaloacetate + GTP
Phosphoenolpyruvate
2 – phosphoglycerate
3 – phosphoglycerate + ATP
1,3 – bisphosphoglycerate + NADH
Glyceraldehyde 3 – PO4
G3-P + DHAP
Fructose 1,6 bisphosphate
Fructose 6 – phosphate
Glucose 6 – phosphate
PRODUCTS
Oxaloacetate + ADP + Pi
Phosphoenolpyruvate + GDP
2 – phosphoglycerate
3 - phosphoglycerate
1,3 – bisphosphoglycerate
Glyceraldehyde 3 – PO4
Dihydroxyacetone PO4
Fructose 1,6 bisphosphate
Fructose 6 – phosphate
Glucose 6 – phosphate
GLUCOSE
 GLYCOGEN
HO

α (16)glycosidic bond
C H
2

O
HO
CH
2

O
O

O
HOCH2 HOCH2 HOCH2 HOCH2 HOCH2 HOCH2 HOCH2

O O O O O O O

O O O O O O

α 14 glycosidic bond

 GLYCOGEN SYNTHESIS
GLYCOGENESIS
Phosphorylation of glucose
Requires activated glucose
UDP – Glucose
UDP – Glu pyrophosphorylase
GLYCOGENIN
332 amino acids
Self-glucosylating enzyme
Glycogen primer
GLYCOGEN SYNTHASE Reaction
GLYCOGEN
SYNTHASE
CH OH
2

O
4 OH 1 U
HO O P P CH2OH CH2OH CH2OH
HO
O O O
4 OH 1 4 OH 1 4 OH 1
O O O HO O O
HO
HO HO HO

GLYCOGEN
GLYCOGENIN
+1
 GLYCOGEN SYNTHESIS
GLUCOSE
ATP
HEXOKINASE
ADP

GLUCOSE 6 – PO4
PHOSPHOGLUCOMUTASE

Glucose 1 - PO4
UTP
UDP-Glc PYROPHOSPHORYLASE
PPi

UDP - GLUCOSE
(Glucose)n
GLYCOGEN SYNTHASE
(Glucose)n +1

GLYCOGEN
 BRANCH Formation
α 1, 6 – glycosidic bond
Branching enzyme
amylo 1,4 1,6 transglycosylase
Transfers terminal residues
6 -7 residues O
O
O
O
O
O
O
O

BRANCHING O
O

O O O
ENZYME
O O O O O
O
4 1
O O O O O O O O O
 GLYCOGEN SYNTHESIS

O O O O O

O O O O O

O O O O
4 1
O O O O
GLYCOGEN DEGRADATION
GLYCOGENOLYSIS
Phosphorolysis
Requires inorganic phosphate
α 1, 4 – glycosidic bond
Glucose 1 - phosphate
GLYCOGEN PHOSPHORYLASE
GLYCOGEN
PHOSPHORYLASE

HPO4 P

CH2OH CH2OH CH2OH CH2OH

O O O O
4 OH 1 4 OH 1 4 OH 1 4 OH 1

HO O HO O HO O O
HO HO HO HO

GLYCOGEN
GLYCOGEN- 1
 DEBRANCHING ENZYME
GLYCOGEN
GLUCAN
PHOSPHORYLASE
TRANSFERASE

O O O O O O O
O
O O O O O
Amylo 1 – 6 O O O

Glucosidase O O O O O
4 1
O O O O O
 GLYCOGENOLYSIS

PHOSPHORYLASE
P

GLUCAN
TRANSFERASE

H2O
α 1,6 GLUCOSIDASE
P
 GLYCOGEN METABOLISM
Glycogen breakdown requires the interplay of
GLYCOGEN PHOSPHORYLASE,
OLIGOTRANSFERASE, and α – 1, 6
GLUCOSIDASE

Glycogen is synthesized by a different pathway

involving GLYCOGEN SYNTHASE and a
BRANCHING ENZYME.

SYNTHESIS and DEGRADATION are

RECIPROCALLY REGULATED.
 CARBOHYDRATES
function
are
Structure
Organic Energy
compounds
releasing
derivatives Gluco-
substrates neogenesis
Polyhydroxyl
TCAC
alcohols
Monosaccharides oxidized Glycolysis
classified as
precursors of HMP Shunt
Glycogen
Disaccharides Hexose
Transporters

Polysaccharides as Absorbed by
STARCH
hydrolyzed Amylases and
Oligosaccharidases