1. Glyconeogenesis

2. Origin of blood glucose
Food
Glycogen
(liver)
Gluconeogenesis
(liver)
Blood sugar

3. 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

4. Synthesis of glucose – non carbohydrate precursors
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

5. Gluconeogenesis 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

6. DG of glycolysis (glucose à pyruvate) – 20 kcal/mole
Glyconeogenesis
DG of glycolysis (glucose à pyruvate) – 20 kcal/mole
Decrease in free energy in three stages
3 different „ways”

7. Irreversible steps
In glycolysis
In glyconeogenesis

9. 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

10. Pyruvate à oxalacetate à phosphoenolpyruvate
Pyruvate-carboxylase
Pyruvate + CO2 + ATP + H2O à oxaloacetate + ADP + Pi + 2H+
Phosphoenolpyruvate carboxykinase TP
oxaloacetate + GTP ó PEP + GDP + CO2

13. Pyruvate carboxylase
Intramitochondrial
Prosthetic group: biotin

14. Signal – for more oxaloacetate
Allosteric activator: Acethyl~CoA
Anaplerotic reaction
Signal – for more oxaloacetate

16. Oxalacetate Gluconeogenesis Citric acid cycle Low amount of ATP
High amount of ATP
Gluconeogenesis
Citric acid cycle

17. 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

18. Plasmamembrane of hepatocytes
Glucose-6-P
GluT7
Glucse-6-phosphatase
Glucose Pi
ER-lumen
GluT7
Cytosol
GluT2
Plasmamembrane of hepatocytes
Bloodplasma

19. 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

20. Citoplazmatikus PEP karboxikináz
NADH + H+
Citoplazmatikus PEP karboxikináz
PEP
NAD+
Oxálacetát
Malát
CO2
Malát
PEP
NAD+
Mitokonriális
PEP
karboxikináz
CO2
NADH + H+
Oxálacetát
Oxálacetát
Piruvát karboxiláz
CO2
CO2
Piruvát
Piruvát
Mitokondrium
Piruvát
Citoszól
Piruvát
NADH + H+
NAD+
Laktát

23. 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

24. Blood Blood Glucose Work (2) ADP + (2) Pi Glycolysis (2) ATP Lactate
(2) H+
Blood

25. Cori cycle Prevents lactic acidosis follow the glycolysis Liver
Musle, red blood cells
Glucose
Glucose
pyruvate
Lactic acid
Lactic acid
Prevents lactic acidosis follow the glycolysis

26. Alanin cyclus Transport of aminoacids in nontoxic form Liver Muscle
urea
Glucose
Glucose
Amino acid
NH2
NH3
Piruvate
Glutamate
glutamate
Piruvate
Alanin
a-ketoglutarate
a-ketoglutarate
Alanin
Transport of aminoacids in nontoxic form

28. Glucose tolerance test