glyconeogenesis. origin of blood glucose foodglycogen (liver) gluconeogenesis (liver) blood sugar
TRANSCRIPT
GlyconeogenesisGlyconeogenesis
Origin of blood glucoseOrigin of blood glucose
Food Glycogen(liver)
Gluconeogenesis(liver)
Blood sugar
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
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
• 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
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”
Irreversible steps
In glycolysis
In glyconeogenesis
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
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
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
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
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
OxOxalacetatealacetate
GluconeogenesisGluconeogenesis Citric acid cycleCitric acid cycle
High amount of High amount of ATP ATP Low amount ofLow amount of ATP ATP
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
Bloodplasma
Plasmamembrane of hepatocytes
GluT2Cytosol
ER-lumenER-lumen
Glucose-6-P
Glucse-6-phosphatase
Glucose Pi
GluT7
GluT7
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
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
BloodG
lycolysis
Lactate (2) H+
(2) ADP + (2) Pi
(2) ATP
Blood Glucose
Work
Cori cycle
Glucose Glucose
Lactic acid Lactic acid
pyruvate
Liver Musle, red blood cells
Prevents lactic acidosis follow the glycolysis
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
Glucose tolerance test