Download - Glyconeogenesis. Origin of blood glucose FoodGlycogen (liver) Gluconeogenesis (liver) Blood sugar
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GlyconeogenesisGlyconeogenesis
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Origin of blood glucoseOrigin of blood glucose
Food Glycogen(liver)
Gluconeogenesis(liver)
Blood sugar
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Decrease of blood sugarDecrease of blood sugar
1. Disfunction of brain• Confusion coma
• In the absence of alternative substrate - serious consequences (ketonbodies)
• . diabetes, overdose of insulin
• Cramps
2. Sympathetic exitement• hyperventillation, cold sweat
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GluconeogenesisGluconeogenesis
• Synthesis of glucose – non carbohydrate precursors– Daily utilisation of glucose: 160 g/day– Glucose - Brain : 120 g/day
• In humours 20 g
• In glycogen 190 g
• Reserves for 24 hours in fasting
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• Gluconeogenesis > fasting for 24 hours• Intensive excercise• Source:
– Lactic acid– aminoacids– Glycerol
• Organ:– Liver– Kidney (1/10)– Some in brain, in heartmuscle in striated muscle
GluconeogenesisGluconeogenesis
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GlyconeogenesisGlyconeogenesis
G of glycolysis (glucose G of glycolysis (glucose pyruvate) – 20 pyruvate) – 20 kcal/molekcal/mole
• Decrease in free energy in three stagesDecrease in free energy in three stages
• 3 different „ways”3 different „ways”
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Irreversible steps
In glycolysis
In glyconeogenesis
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Irreversible steps of glycolysis
1. Glucose + ATP glucose-6-P + ADP
hexokinase
2. Fruktose-6-P + ATP fructose-1,6-diP + ADP
phosphofructokinase
3. PEP + ADP pyruvate + ATP
Piruvate kinase
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Pyruvate oxalacetate phosphoenolpyruvate
PPyyruvruvateate + CO + CO22 + ATP + H + ATP + H22O O oxaloacetateoxaloacetate + ADP + P + ADP + Pi i + +
2H2H++
oxaloacetateoxaloacetate + GTP PEP + GDP + CO2
Pyruvate-carboxylase
Phosphoenolpyruvate carboxykinase
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C
CH3
C
O
O
OC
CH2
COO-
COO-
OCO2
C
CH2
H
C
O
O
O P
O
O
O
CO2
piruvát oxálacetát
+
foszfoenol-piruvát
pyruvate-carboxylase phosphoenol-pyruvate-carboxykinase
Go` = + 0.2 kcal / mole
Pyruvatkinase 7.5 kcal / mole
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CH2 CH2 CH2 CH2 CH
CH
CH2 SCH
CH
N NHC
O
CH2 CH2 CH2 CH2 C
O
NH
NH
C O
C
O
OLysineBiotin
Pyruvate carboxylasePyruvate carboxylase
Intramitochondrial
Prosthetic group: biotin
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Lys Biotin Lys Biotin
CO2
ATP ADP + Pi
CO2
C
CH3
C
O
O
O
C
CH2
COO-
COO-
O
Lys Biotin
- 4.7 kcal/mól
AllostAllosteeriricc a acctivtivaator: Acettor: Acethyhyl~CoAl~CoA
Anaplerotic reaction Signal – for more oxaloacetate
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OxOxalacetatealacetate
GluconeogenesisGluconeogenesis Citric acid cycleCitric acid cycle
High amount of High amount of ATP ATP Low amount ofLow amount of ATP ATP
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Irreversible steps of glyconeogenesis
2. fructose-1,6-diP + H2O fructose-6-P +Pi
3. glucose-6-P + H2O glucose +Pi
Fructose-1,6-diP
Glucose-6-phosphatase
Absence in brain and muscleAbsence in brain and muscle
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Bloodplasma
Plasmamembrane of hepatocytes
GluT2Cytosol
ER-lumenER-lumen
Glucose-6-P
Glucse-6-phosphatase
Glucose Pi
GluT7
GluT7
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The gluconeogenesis is „expensive”
2 pyruvate + 4 ATP + 2 GTP + 2 NADH + 4 H2O
Glucose + 4 ADP + 2 GDP + 2 NAD+ + 2 H+
Glycolysis
Glucose + 2 ADP + 2 Pi + 2 NAD+
2 pyruvate+ 2 ATP + 2 NADH + 2H++ 2 H2O
Irreversible
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Glucoplastic aminoacids
• Pyruvate– Alanine– Cystein– Glycine– Serine– Triptophane
• .-ketoglutarate– Arginine– Glutamate– Glutamine– Hisztidine– Proline
• Succinyl-CoA– Isoleucine– Metionine– Treonine– Valine
• Fumarate– Fenilalanin– Tirozin
• Oxalacetate– Aspartate– Asparagine
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BloodG
lycolysis
Lactate (2) H+
(2) ADP + (2) Pi
(2) ATP
Blood Glucose
Work
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Cori cycle
Glucose Glucose
Lactic acid Lactic acid
pyruvate
Liver Musle, red blood cells
Prevents lactic acidosis follow the glycolysis
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Alanin cyclus
Glucose Glucose
Piruvate Alanin
Piruvate
Liver Muscle
Transport of aminoacids in nontoxic form
Alanin-ketoglutarate
glutamate
NH3
urea Amino acid
NH2
Glutamate
-ketoglutarate
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Glucose tolerance test