Glyconeogenesis

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

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

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

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

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”

Irreversible steps In glycolysis In glyconeogenesis

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

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

Pyruvate carboxylase Intramitochondrial Prosthetic group: biotin

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

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

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

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

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

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

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

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

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

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

Glucose tolerance test