Biochemistry - Glycogen Flashcards
Glycogen
- Water insoluble
- Rapidly accessed
- Protects osmotic pressure of the cell
- Glycogenin is the protein in the middle of the Glycogen polymer
Glycogen Structure
- alpha 1-4 bonds link glucose molecules in a line
- alpha 1-6 bonds link glucose branches together
- WORK UNTIL 4 AND BRANCH OUT AT 6 (Cno.)
- Glucose molecules are attached and broken off at the non reducing ends
Glycogenesis
- Glucose comes through the Hepatic portal vein in the liver and enters a hepatocyte through a glucose transporter
- Hexokinase or Glucokinase (fast, higher Vmax) will phosphorylate the glucose trapping it in the cell
- Phosphoglucomutase moves from G6P to G1P which commits the molecule to glycogen synthesis
- G1P + UTP = UDPG using pyrophosphorylase (2xP) this process is Endergonic (energy investment)
- Glycogen synthase attaches UDPG to the glycogenin
UTP/UDP
- UTP has the same energy as ATP
- UDP binds to the G1P and targets it for glycogen synthesis
Glycogen Branches
- Branches grow to a set length of UDP glucose
- Branching enzyme which takes part of an existing branch and moves it exactly 4 units up towards the core (steric hinderance) making glycogen dense
- Efficient storage
What triggers Glycogenolysis
- Stimulated by adrenaline
- Extreme unger of exhaustion
Enzymes used:
1. Glycogen phosphorylase (inhibited by ATP, glucose and G6P)
2. Glycogen de-branching enzyme (2 of these)
3. Phosphoglucomutase - Broken down from the non reducing end
Glycogenolysis
- Phosphorylyisis
- Glycogen phosphorylase does not require ATP but binds phosphate to break the bind making G1P - Once there are 4 units left on the branch the deb ranching enzyme acts as a transferase that moves 3 glycosyl units to the main chain so they can undergo phosphorylysis
- Hydrolysis the last alpha-1,6 link and that glucose is lost from the cell or ATP must be used to trap it - Phosphoglucomutase converts G1P to G6P
- first step of glycolysis is bypassed so we yield 1 extra ATP
Phosphorylyisis? Why not hydrolysis?
1) Hydrolysis will leave an un phosphorylated glucose
2) Ensures released glucose is charged and trapped in cells (important in muscles)
3) It also saves an ATP each time! Pi is used directly
Glucose 6-phosphatase
- in liver and kidney
- removes phosphate and glucose can move into the blood to be used by other tissues
epinephrine/adrenaline effect
- Adrenaline causes cAMP to be made which is a messenger to activate Protein Kinase A
- Protein Kinase A activates Phosphorylase A from B which will release glucose
- Protein Kinase A can also inactive Glycogen Synthase A producing B which will stop the production of glycogen
Von Gierke’s Disease
Type I GSD glucose 6-phosphatase mutation
- can’t release glucose from liver
- Hypoglycaemia
- Excess G6P shunted to triglycerides, hyperlipidaemia
- Elevated lactate during fasting
- Gout (hyperuricaemia)
- Enlarged liver and kidneys
- Treatment fructose and other carbohydrates
Mc Ardle’s Disease
- Glycogen in muscle, but severe muscle cramps?
- Lack of glucose release, little glycogen phosphorylase activity in muscle (isoform called “myophosphorylase”)
Glucose Storage Diseases (GSD)
- 11 known types of GSD
- Incidence ~ 2.5 children / 100,000 births
- 7 result in muscle weakness or wastage
- 5 result in enlarged livers
Gluconeogenesis
- The synthesis of glucose
- Steps are the reverse of glycolysis
- Some irreversible steps in glycolysis that we must bypass i.e. 1,3,9,10
Important enzymes in gluconeogenesis
All use energy - consume 12 ATP
- Pyruvate Carboxylase (Bypass 1 Matrix)
- Phosphenolpyruvate carboxykinase (PEPCK) (Bypass 1 Cytosol)
- Fructose 1,6-bisphosphate (Bypass 2 Cytosol)
- Glucose 6-phosphate (Bypass 3 ER)
What can we use for Gluconeogenesis
- Lactate can be converted to pyruvate/alaine (Cori cycle)
- Amino acids (except leucine and lysine) can be converted to pyruvate or oxaloacetate
- Glycerol from fats can be converted to Dihydroxyacetone phosphate DHAP
- CAC intermediates can be converted to citrate, oxaloacetate, malate
How does Gluconeogenesis happen
- 2 Pyruvate (mitochondria) using pyruvate carboxylate are converted to 2 oxaloacetate
- 2 oxaloacetate are converted to 2 Malate and moved into the cytosol then converted back to 2 oxaloacetate
- Reverse steps of glycolysis and Glycerol enters at step 4
- Glucose
Non-Equilibrium Enzymes
Non-reversable steps of glycolysis we need bypasses
- Bypass 3 - hexakinase
- Bypass 2 - phosphofructakinase
- Bypass 1 - pyruvate kinase
Equilibrium Enzymes
- lactate dehydrogenase
- malate dehydrogenase
