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