Metabolism of glycogen. Regulation of glycogen metabolism Regulating site for glycogen synthesis...
-
Upload
marybeth-daniel -
Category
Documents
-
view
240 -
download
2
Transcript of Metabolism of glycogen. Regulation of glycogen metabolism Regulating site for glycogen synthesis...
Regulation of glycogen metabolism
• Regulating site for glycogen synthesis
Glycogen synthase
• Regulating site for glycogen catabolism
Glycogen phosphorylase
Glycogen Phosphorylase AMP activates Phosphorylase
ATP & glucose-6-phosphate inhibit Phosphorylase
Thus glycogen breakdown is inhibited when ATP and glucose-6-phosphate are plentiful.
Glycogen Synthase Activated by glucose-6-P (opposite of effect on Phosphorylase).
Thus Glycogen Synthase is active when high blood glucose leads to elevated intracellular glucose-6-P.
Regulation by hormones
Glucagon and epinephrine:
• Inhibit glycogen synthase
• Activate glycogen phosphorylase
• Increase glycogen catabolism and increase blood glucose
Insulin:
• Inhibit glycogen phosphorylase
• Activate glycogen synthase
• Increase glycogen synthesis and decrease blood glucose
Glycogen Function
• In liver – The synthesis and breakdown of glycogen is regulated to maintain blood glucose levels.
• In muscle - The synthesis and breakdown of glycogen is regulated to meet the energy requirements of the muscle cells.
Gluconeogenesis
• A metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates.
• It is one of the two main mechanisms the body uses to keep blood glucose levels from dropping too low .
• In animals, gluconeogenesis takes place mainly in the liver.
• This process occurs during periods of fasting, starvation, or intense exercise.
Irreversible glycolytic stepsbypassed
1. Hexokinase
2. Phosphofructokinase-1
3. Pyruvate kinase (PyrK)
by Glucose-6-phosphatase
by Fructose 1,6-bisphosphatase
by Pyruvate Carboxylase and Phosphoenolpyruvate carboxykinase
Glycolysis Gluconeogenesis
Glucose-6-Phosphatase catalyzes: glucose-6-phosphate + H2O glucose + Pi
• This is primarily a function of the liver to buffer blood glucose levels
• Glucose-6-Phosphatase is NOT present in brain and muscle!
Bypass 1:
Bypass 3:
Pyrovate carboxylase and PEP carboxykinase catalyze:
Pyruvate + ATP+ GTP PEP + ADP + GDP + Pi + CO2
PEP carboxykinase locates in bothcytosol and mitochondral. So there are two ways to transfer pyruvate to PEP.
Lactate feed into gluconeogenesis through pyruvate.
Lactate dehydrogenase
Liver is the major source of blood glucose from gluconeogenesis
Is the primary gluconeogenic organ
Produces glucose for export to brain, muscle, RBC’s
Uses many small metabolites and amino acids to feed gluconeogenesis
Liver function is highly sensitive to insulin & glucagon
Cori CF
• Lactate and glucose shuttle between active muscle/RBC and liver
•Liver gluconeogenesis supplies the blood glucose for use by muscle, RBC’s and brain (120 g/day)
• Note: the brain fully oxidizes glucose, so it does not funnel back lactate
• The liver can also use the amino acid Alanine similarly to Lactate
• Following transamination to pyruvate, gluconeogenesis allows the liver to convert it to glucose for secretion into the blood
Regulation of gluconeogenesis
To prevent the waste of a futile cycle, Glycolysis & Gluconeogenesis are reciprocally regulated.
F-1,6-Bisphosphatase is the most important control site in Gluconeogenesis.
Reciprocal regulation by ATP/AMP AMP inhibits Fructose-1,6-bisphosphatase but activates
Phosphofructokinase ATP inhibits Phosphofructokinase but activate Fructose-1,6-
bisphosphatase In high ATP/AMP ratio: stimulate gluconeogenesis In low ATP/AMP ratio: stimulate glycolysis
Reciprocal regulation by fructose-2,6-bisphosphate:
Fructose-2,6-bisphosphate stimulates Glycolysis.
Fructose-2,6-bisphosphate activates Phosphofructokinase-1.
Fructose-2,6-bisphosphate inhibits Fructose-1,6-bisphosphatase.
Reciprocal regulation by hormones Phosphofructokinase-1 (PFK-1)
Induced in feeding by insulin Repressed in starvation by glucagon
Fructose-1,6-bisphosphase Repressed in feeding by insulin Induced in starvation by glucagon
So: Insulin activates glycolysis but inhibits gluconeogenesis; Glucagon activates gluconeogenesis but inhibits glycolysis.
The first enzyme to act on galactose is galactokinase. This converts galactose into galactose-1-phosphate.
Galactose-1-phosphate uridyl transferase produces UDP-galactose and Glucose-1-Phosphate from galactose-1-phosphate and UDP-glucose.
UDP-Galactose