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GLUCONEOGENESIS
Biosynthesis of glucose
3 – 4 carbon noncarbohydrate precursors
Enzymes located in the cytosol
Gluconeogenic organsLiver
Kidney cortex
Fates Catabolism by nervous tissue
Utilization by skeletal muscles
GLUCONEOGENESIS
SUBSTRATES GLUCOGENIC AMINO ACIDS
LACTATE
GLYCEROL
PROPIONATE
PRECURSORSGLUCOSE
Fructose 1,6 - bisphosphate
Dihydroxyacetone phosphate
Glyceraldehyde 3 - phosphate
GLYCEROL
PYRUVATE
Glycerol 3 - phosphate Phosphoenolpyruvate
Oxaloacetate
ALANINE
LACTATE
Other amino acids
PROPIONATE
SUCCINYL-CoA
CORI CYCLESKELETAL MUSCLE LIVERBLOOD
GLUCOSE
2 PYRUVATE
2 LACTATE
GLUCOSE
2 PYRUVATE
2 LACTATE
6 ATP2ATP
1,3 Bisphosphoglycerate
3 - Phosphoglycerate
2 - Phosphoglycerate
Glyceraldehyde 3 - phosphate
Phosphoenolpyruvate
GLUCOSE
DHAP
Fructose 1,6 - bisphosphate
PYRUVATE
OXALOACETATE
PEP
PYRUVATE
LACTATE
OAA
GLUCOSE - ALANINE CYCLESKELETAL MUSCLE LIVERBLOOD
GLUCOSE
2 PYRUVATE
2 ALANINE
GLUCOSE
2 PYRUVATE
2 ALANINE
6 ATP2ATP
2NH2
2NH2
UREA
2 Oxaloacetate
Glucose 6 - phosphate
GLUCOSE
2 PYRUVATE
Fructose 6 - phosphate
Fructose 1,6 - bisphosphate
Phosphoenolpyruvate
ATP
ATP
ATP
ATP
2GTP
2ATP
2ATP
2NADH2NADH
1
2H2O
H2O 3
BYPASS REACTIONS
PYRUVATE to PHOSPHOENOLPYRUVATEPYRUVATE 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
CH2
C O
C O
O
CH2
C O
C O
OP
CO2
OXALOACETATE
C O
O
PEP CARBOXYKINASE
PHOSPHOENOLPYRUVATE
PP
G
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 REACTIONSREACTANTS 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
O
HOCH2
O
HOCH2
O
O
HOCH2
O
O
HOCH2
O
O
HOCH2
O
O
HOCH2
O
O
HOCH2
O
O
HOCH2
O
HOCH2
O
O
14 glycosidic bond
(16)glycosidic bond
GLYCOGEN
GLYCOGEN SYNTHESIS
GLYCOGENESISPhosphorylation of glucose
Requires activated glucose UDP – Glucose
UDP – Glu pyrophosphorylase
GLYCOGENIN 332 amino acids
Self-glucosylating enzyme
Glycogen primer
GLYCOGEN SYNTHASE ReactionGLYCOGEN SYNTHASE
HO
O
CH2OH
14
HO
OH
O
HO HO
O
CH2OH
14
HO
OHO
O
CH2OH
14
HO
OH
O
O
CH2OH
14
HO
OHO
PP
U
O
GLYCOGENINGLYCOGEN + 1
GLYCOGEN SYNTHASE
HO
O
CH2OH
14
HO
OH
O PP
U
O
GLYCOGEN SYNTHESIS
UDP - GLUCOSE
Glucose 1 - PO4
GLUCOSE 6 – PO4
GLUCOSE
ATP
ADP
UTP
PPi
GLYCOGEN
(Glucose)n
(Glucose)n +1
HEXOKINASE
UDP-Glc PYROPHOSPHORYLASE
PHOSPHOGLUCOMUTASE
GLYCOGEN SYNTHASE
1, 6 – glycosidic bond
Branching enzyme amylo 1,4 1,6 transglycosylase
Transfers terminal residues
6 -7 residues
BRANCH Formation
OOOO
O
O
O O O O
BRANCHING ENZYME
O14
O
OOO
OOO
O
O
O
O
OO
O
O
O
O
GLYCOGEN SYNTHESIS
O
O
O
O
O
O
OOOO
O
O
O O O O
O14
O
OOO
OOO
O
O
O
O
O
O
GLYCOGEN DEGRADATION
GLYCOGENOLYSIS Phosphorolysis
Requires inorganic phosphate 1, 4 – glycosidic bond
Glucose 1 - phosphate
HO HO
O
CH2OH
14
HO
OHO
O
CH2OH
14
HO
OH
O
O
CH2OH
14
HO
OHOO
GLYCOGENGLYCOGEN - 1
GLYCOGEN PHOSPHORYLASE
HO
O
CH2OH
14
HO
OH
GLYCOGEN PHOSPHORYLASE
PHPO4
Amylo 1 – 6 Glucosidase
DEBRANCHING ENZYME
O14
O
O
O
O
O
O
O
GLUCAN TRANSFERASE
O
O
O
O
O
OO
O O
O
O
O
O
O
O
O
GLYCOGEN PHOSPHORYLASE
O
O
GLYCOGENOLYSIS
PHOSPHORYLASE
GLUCAN TRANSFERASE
1,6 GLUCOSIDASEP
P
P
H2O
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
HMP Shunt
Glycolysisoxidized
Energy Structure
function
TCAC
releasingGluco-
neogenesissubstrates
STARCH
Monosaccharides
Glycogen
as
areOrganic
compounds
Polyhydroxyl alcohols
Disaccharides
Polysaccharides
derivatives
classified as
precursors of
Amylases and Oligosaccharidases
hydrolyzed
Hexose Transporters
Absorbed by
