Glyconeogenesis

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Glyconeogenesis
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Origin of blood glucose
Food
Glycogen (liver)
Gluconeogenesis (liver)
Blood sugar
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Decrease of blood sugar

• Disfunction of brain
• Confusion à coma
• In the absence of alternative substrate -
  serious consequences (ketonbodies)
• .à diabetes, overdose of insulin
• Cramps
• Sympathetic exitement
• hyperventillation, cold sweat

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Gluconeogenesis

• 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

• Gluconeogenesis gt fasting for 24 hours
• Intensive excercise
• Source
• Lactic acid
• aminoacids
• Glycerol
• Organ
• Liver
• Kidney (1/10)
• Some in brain, in heartmuscle in striated muscle

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Glyconeogenesis

• DG of glycolysis (glucose à pyruvate) 20
  kcal/mole
• Decrease in free energy in three stages
• 3 different ways

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Irreversible steps
In glycolysis
In glyconeogenesis
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Irreversible steps of glycolysis
hexokinase
1. Glucose ATP à glucose-6-P ADP
phosphofructokinase
2. Fruktose-6-P ATP à fructose-1,6-diP ADP
Piruvate kinase
3. PEP ADP à pyruvate ATP
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Pyruvate à oxalacetate à phosphoenolpyruvate
Pyruvate-carboxylase
Pyruvate CO2 ATP H2O à oxaloacetate ADP
Pi 2H
Phosphoenolpyruvate carboxykinase
oxaloacetate GTP ó PEP GDP CO2
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Pyruvate carboxylase
Intramitochondrial
Prosthetic group biotin
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Allosteric activator AcethylCoA
Anaplerotic reaction
Signal for more oxaloacetate
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Oxalacetate
Low amount of ATP
High amount of ATP
Gluconeogenesis
Citric acid cycle
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Irreversible steps of glyconeogenesis
Fructose-1,6-diP
2. fructose-1,6-diP H2O à fructose-6-P Pi
Glucose-6-phosphatase
3. glucose-6-P H2O à glucose Pi
Absence in brain and muscle
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Glucose-6-P
GluT7
Glucse-6-phosphatase
Glucose
ER-lumen
Pi
GluT7
Cytosol
GluT2

Plasmamembrane of hepatocytes
Bloodplasma
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The gluconeogenesis is expensive
2 pyruvate 4 ATP 2 GTP 2 NADH 4 H2O àà
à à Glucose 4 ADP 2 GDP 2 NAD 2 H
Irreversible
Glycolysis
Glucose 2 ADP 2 Pi 2 NAD à à
à à 2 pyruvate 2 ATP 2 NADH 2H 2 H2O
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NADH H
Citoplazmatikus PEP karboxikináz
PEP
Oxálacetát
NAD
Malát
CO2
Malát
PEP
NAD
Mitokonriális PEP karboxikináz
CO2
NADH H
Oxálacetát
Oxálacetát
Piruvát karboxiláz
CO2
CO2
Piruvát
Piruvát
Mitokondrium
Citoszól
Piruvát
Piruvát
NADH H
NAD
Laktát
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Glucoplastic aminoacids

• Pyruvate
• Alanine
• Cystein
• Glycine
• Serine
• Triptophane
• .a-ketoglutarate
• Arginine
• Glutamate
• Glutamine
• Hisztidine
• Proline

• Succinyl-CoA
• Isoleucine
• Metionine
• Treonine
• Valine
• Fumarate
• Fenilalanin
• Tirozin
• Oxalacetate
• Aspartate
• Asparagine

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Blood
Glucose
Work
(2) ADP (2) Pi
Glycolysis
(2) ATP
Lactate
(2) H
Blood
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Cori cycle
Liver
Musle, red blood cells
Glucose
Glucose
pyruvate
Lactic acid
Lactic acid
Prevents lactic acidosis follow the glycolysis
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Alanin cyclus
Liver
Muscle
Glucose
Amino acid
Glucose
urea
NH2
Piruvate
NH3
Glutamate
glutamate
Piruvate
Alanin
a-ketoglutarate
a-ketoglutarate
Alanin
Transport of aminoacids in nontoxic form
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Glucose tolerance test