Gluco Neo Genesis
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Transcript of Gluco Neo Genesis
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
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 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
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• GLYCOGENESIS
– Phosphorylation 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
BRANCH Formation• 1, 6 – glycosidic bond• Branching enzyme
– amylo 1,4 1,6 transglycosylase• Transfers terminal residues• 6 -7 residues
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 METABOLISMGlycogen 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
