Gluconeogenesis
Gluconeogenesis
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
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
Glyceraldehyde 3 - phosphate
PYRUVATE
1,3 Bisphosphoglycerate
PYRUVATE
3 - Phosphoglycerate
2 - Phosphoglycerate
Phosphoenolpyruvate
OAA
OXALOACETATE
PEP
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
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
Oxaloacetate + ADP + Pi
Oxaloacetate + GTP
Phosphoenolpyruvate + GDP
Phosphoenolpyruvate
2 phosphoglycerate
2 phosphoglycerate
3 - phosphoglycerate
3 phosphoglycerate + ATP
1,3 bisphosphoglycerate
Glyceraldehyde 3 PO4
Glyceraldehyde 3 PO4
Dihydroxyacetone PO4
G3-P + DHAP
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
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