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
phosphate

Glyceraldehyde 3 - phosphate

Phosphoenolpyruvate

Glycerol 3 - phosphate

SUCCINYLCoA

Oxaloacetate
GLYCEROL
ALANINE
LACTATE

PYRUVATE

Other
amino acids

CORI CYCLE
SKELETAL MUSCLE

GLUCOSE

BLOOD

LIVER

GLUCOSE

2ATP
6 ATP

2 PYRUVATE

2 PYRUVATE

2 LACTATE

2 LACTATE

GLUCOSE

Fructose 1,6 - bisphosphate

LACTATE
DHAP

Glyceraldehyde 3 - phosphate

PYRUVATE
1,3 Bisphosphoglycerate

PYRUVATE
3 - Phosphoglycerate

2 - Phosphoglycerate

Phosphoenolpyruvate

OAA

OXALOACETATE

PEP

GLUCOSE - ALANINE CYCLE

SKELETAL MUSCLE

GLUCOSE

BLOOD

LIVER

GLUCOSE

2ATP
6 ATP

2 PYRUVATE

2 PYRUVATE
2NH2

2NH2

2 ALANINE

2 ALANINE

UREA

GLUCOSE
ATP

H2O

Glucose 6 - phosphate
Fructose 6 - phosphate
H2O

ATP

Fructose 1,6 - bisphosphate

2NADH

2NADH
2ATP

ATP

Phosphoenolpyruvate
2GTP
ATP

2 Oxaloacetate
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
O

PEP
CARBOXYKINASE
G
CO2

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

PRODUCTS

Pyruvate + CO2 + ATP +H2O

Oxaloacetate + ADP + Pi

Oxaloacetate + GTP

Phosphoenolpyruvate + GDP

Phosphoenolpyruvate

2 phosphoglycerate

2 phosphoglycerate

3 - phosphoglycerate

3 phosphoglycerate + ATP

1,3 bisphosphoglycerate

1,3 bisphosphoglycerate + NADH

Glyceraldehyde 3 PO4

Glyceraldehyde 3 PO4

Dihydroxyacetone PO4

G3-P + DHAP

Fructose 1,6 bisphosphate

Fructose 1,6 bisphosphate

Fructose 6 phosphate

Fructose 6 phosphate

Glucose 6 phosphate

Glucose 6 phosphate

GLUCOSE

GLYCOGEN
HO
CH

(16)glycosidic bond

HO
CH

HOCH2

HOCH2

HOCH2

HOCH2

O
O

HOCH2

O
O

14 glycosidic bond

HOCH2

O
O

HOCH2

O
O

O
O

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

HO

U
O

CH2OH

HO

CH2OH

CH2OH

4 OH 1

4 OH 1

4 OH 1

O HO

HO
HO

O
HO

GLYCOGEN
GLYCOGENIN
+1

O
HO

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
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
ENZYME
O
O

O
O

4
O

GLYCOGEN SYNTHESIS
O
O

O
O

O
4

GLYCOGEN DEGRADATION
GLYCOGENOLYSIS
Phosphorolysis
Requires inorganic phosphate
1, 4 glycosidic bond
Glucose 1 - phosphate

GLYCOGEN PHOSPHORYLASE
GLYCOGEN
PHOSPHORYLASE
HPO4

CH2OH

CH2OH

CH2OH

CH2OH

4 OH 1

4 OH 1

4 OH 1

4 OH 1

O HO

HO
HO

O HO
HO

O
HO

GLYCOGEN
GLYCOGEN- 1

O
HO

DEBRANCHING ENZYME
GLYCOGEN
GLUCAN
PHOSPHORYLASE
TRANSFERASE

O
O

O
O

Amylo 1 6
Glucosidase

O
O

O
O

O
O

O
O

4
O

GLYCOGENOLYSIS
P

PHOSPHORYLASE
P

GLUCAN
TRANSFERASE

1,6 GLUCOSIDASE

H2O
P

GLYCOGEN METABOLISM
Glycogen breakdown requires the interplay of
GLYCOGEN PHOSPHORYLASE,
OLIGOTRANSFERASE, and 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
Organic
compounds

Energy
releasing

derivatives

substrates

TCAC

Polyhydroxyl
alcohols
classified as

Structure

Monosaccharides

oxidized

precursors of

Polysaccharides

as

Glycolysis
HMP Shunt

Glycogen

Disaccharides

Gluconeogenesis

Hexose
Transporters
Absorbed by

STARCH
hydrolyzed

Amylases and
Oligosaccharidases