Bioenergetics 8: Gluconeogensis

Question 1

What is glycogens structure

Answer 1

It is insoluble and rapidly accessed. Large glycogen polymers do not attract as much water as glucose. It protects the osmotic pressure of the cell.

Question 2

What is the different roles of liver and muscle

glycogen stores

Answer 2

Glycogen stores in the liver (8-10%) (and a little kidney) is the only one to release glucose to other tissues because it has the G6Phosphatase to release it.
In the muscle it is 1-2% stored
As a tissue liver holds the most of glycogen but as in the body the muscle has the most even though 1-2%

Question 3

Where is glycogen stored in the cell

Answer 3

cytosol

Question 4

What are the hormones that trigger breakdown of glycogen vs hormones that trigger Glycogenesis (synthesis of glycogen)

Answer 4

Breakdown: glucagon,
adrenaline and cortizone
Glycogenesis: insulin

Question 5

Describe the 5 steps of glycogenesis

Answer 5

1. Glucose enters through GLUT transporter and gets phosphorylated by Hexokinase or Glucokinase to be G6P
2. Phosphoglucomutase shifts the Pi group to make Glucose 1 phosphate
3. UPDG Pyrophosphoryalse swaps the Pi for UDP by using up 1 UTP. This is energy investment
4. Glycogen synthase attaches glucose to non reducing end by a1,4 linakges
5. Branching is done by branching enzyme Amyloa(1-4)toa(1-6) transglycoslyase when the glycogen chain is 7-11 glycosyl residues long it moves it 4 up.

Question 6

What is glycogenin

Answer 6

It is an enzyme that encourages the binding of glucose together and the only thing that attaches to the reducing end of glucose straight chains.

Question 7

Describe the 4 steps in Glycogenolysis

Answer 7

1. Glycogen phosphorylase breaks the bonds between glucose (branch) from the non reducing end by phosphorylysis, adding free Pi in the cytosol (not using ATP). This releases G1P. It works until there are 4 glycosyl residues left attached
2. Glycogen debranching enzyme acts as a transferase to move the remaining 3 glycosyl residues to the main branch and hydrolyses the a-1,6 link to free the last glucose which has a phosphate added by the gluco/hexokinase.
3. Phosphoglucomutase makes the G1P to G6P ready for glycolysis or gluconeogenesis
4. Only in the liver and kidneys there is Glucose-6- phosphatase which takes away 1 Pi and therefore makes glucose free to leave to go to other tissues.

Question 8

Why does glycogen phosphorylase break apart glucoses of glycogen branches by phosphorylsis not hydrolysis

Answer 8

Hydrolysis will leave an unphosphorylated glucose which can leave the cell so requires an ATP to phosphorylate it to make it charged to trap it.
However phosphorylysis uses inorganic phosphate directly so saves ATP

Question 9

What is the ATP yield from G3P made from glycogen entering glycolysis

Answer 9

3 ATP as the first step by hexo/glucokinase has been bypassed by a direct use of phosphate

Question 10

What inhibits glycogen phosphoryase

Answer 10

Lots of ATP, glucose and G6P -> products of use of glucosis

Question 11

What is Von Gierkes disease

Answer 11

Type 1 GSD, the most prevalent disease resulting in a mutation in glucose-6-phosphorylase in the liver and kidneys, so while you can store glucose you cannot release it to other tissues.
This results in hypoglycemia, and G6P going to adipogenesis, enlarged kidney and livers, elevated lactate levels.

Question 12

What is Mc Ardle disease

Answer 12

Mutation in myophosphorylase in muscle meaning you can’t breaks down glycogen stores in the muscle. This means that there are excess glycogen stores in muscle and muscle cramps happen. ADP levels rise dramatically then recover somewhat due to glucose coming from liver, proteins and lipids.

Question 13

What are the sources of fuel that can be used in making new glucose (gluconeogenesis)

Answer 13

1. Lactate which can go to pyruvate/alanine in coricycle
2. Amino acids (except leucine, lysine) from proteins
3. Glycerol–>G3P (from TAGS)
4. TCA intermediates (citrate, oxaloacetate, malate)

Question 14

What is the energy investment required for gluconeogenesis

Answer 14

11-12 ATP equivalents

Question 15

What are the 3 bypasses of irreversible reactions in glycolysis and which enzymes are they trying to bypass

Answer 15

1. To bypass pyruvate kinase,
   a) pyruvate in mitochondrial matrix must have a CO2 added by Pyruvate carboxylase (needs ATP) to become oxaloacetate.
   b) Then in the cytosol PEPCK uses a GTP and NADH to make phosphoenolpyruvate from oxaloacetate
2. To bypass phosphofructokinase, need to use fructose-1,6-bisphosphatase to make fructose-6- phosphate
3. To bypass hexo/glucokinase need to use Glucose-6-phosphatase in the liver ER to make glucose

Question 16

What is bypass 3:

Answer 16

Glucose-6-phosphatase

Question 17

How do you regulate making and breaking of glycogen from glucose to avoid futile cycles

Answer 17

Epinephrine/glucagon starts as signal cascade ending in Protein kinase A which

a) activates Phosphorylase kinase which activates glycogen phosphorylase-> for breaking glycogen
b) inactivates glycogen synthase -> stopping making glycogen

Question 18

What stimulates the 3 bypass enzymes of gluconeogenesis

Answer 18

High energy stage
Acetyl CoA and oxaloacetate for pyruvate carboxylase + PEPCK
Citrate for fructose-1,6-phosphatase

Question 19

What inhibits the 3 bypass enzymes of gluconeogenesis

Answer 19

Lots of ADP for pyruvate carboxylase and PEPCK

Lots of ADP, AMP and Fructose-2,6-phosphate