MEH 4. Glycogen And Fat Flashcards
Which tissues have an absolute requirement for glucose as an energy source?
Red blood cells
Neutrophils
Innermost cells of kidney medulla
Lens of the eye
What are the 2 locations of glycogen storage?
- Muscle
2. Liver - hepatocytes
Glycogen is stored as ___________.
Granules
Glycogen is a polymer consisting of chains of which monomer?
Glucose
Which two glycosidic bonds are present in glycogen?
Alpha 1-4 glycosidic bonds between glucose residues.
Alpha 1-6 glycosidic bonds forming branches every 8-10 residues.
Which protein dimer is present at the core of glycogen?
Glycogenin
Outline the first step of glycogen synthesis from glucose, naming the enzyme required.
Glucose + ATP -> Glucose-6-phosphate + ADP.
Hexokinase or glucokinase (in liver)
The second step of glycogenesis converts glucose-6-phosphate to glucose 1-phosphate. Which enzyme is responsible for this?
Phosphoglucomutase ( this step is reversible)
In the 3rd reaction of glycogenesis, what is glucose-1-phosphate converted to?
UDP-glucose
What form of glucose is able to be incorporated to glycogen?
UDP-glucose
Which 2 enzymes are responsible for the addition of UDP-glucose to glycogen?
Glycogen synthase (alpha 1,4 glycosidic bonds) Branching enzyme (alpha-1,6-glycosidic bonds)
Which enzymes are responsible for degradation of glycogen to produce glucose 1-phosophate?
Glycogen phosphorylase
De-branching enzyme
Why is glycogenolysis not simply the reversal of glycogenesis?
Different enzymes are involved in order to allow inhibition of one pathway and stimulation of another.
Why can only liver glycogen (and not muscle glycogen) act as a buffer for blood glucose levels?
In the liver, Glucose 6-phosphate is converted to glucose by glucose-6-phosphatase and exported to blood.
Muscle lacks the enzyme glucose-6-phosphatase, so glucose 6-phosphate enters glycolysis for energy production.
What is the rate limiting enzyme in glycogen synthesis?
Glycogen synthase
What is the rate limiting enzyme in glycogen degradation?
Glycogen phosphorylase
Which 3 hormones regulate glycogen metabolism?
Glucagon, adrenaline and insulin
What effect do glucagon and adrenaline have on glycogen synthase?
Decrease it’s activity
What effect do glucagon and adrenaline have on glycogen phosphorylase?
Increase its activity
What effect does insulin have on glycogen synthase?
Increase its activity
What effect does insulin have on glycogen phosphorylase?
Decreases activity
How does regulation of muscle stores differ to liver stores?
Glucagon has no effect on muscle glycogen stored (no receptors).
AMP is an allosteric activator of muscle glycogen phosphorylase, but NOT the liver form of the enzyme.
How do the mechanisms of glucagon and adrenaline differ to insulin?
Glucagon + adrenaline - phosphorylate
Insulin - de-phosphorylates
Give 2 examples of glycogen storage diseases.
- Von Gierke’s disease
2. McArdle disease
Which enzyme is deficient in von Gierke’s disease?
Glucose 6-phosphatase
Which enzyme is deficient in McArdle disease?
Muscle glycogen phosphorylase
Where does gluconeogenesis occur?
Liver and to a lesser extent in kidney cortex.
What are the 3 major precursors of gluconeogenesis?
- Lactate (from anaerobic glycolysis)
- Glycerol ( from adipose tissue breakdown of triglycerides)
- Amino acids (alanine)
Why is Acetyl CoA unable to be converted to glucose?
Acetyl-CoA cannot be converted to pyruvate. Pyruvate deyhydrogenase enzyme regulated reaction is irreversible.
After how many hours of fasting is gluconeogenesis required?
8 hours
Liver glycogen stores start to deplete at this point and alternative source is required.
What are the 3 key regulatory enzymes in gluconeogenesis?
- PEPCK
- Fructose 1,6-bisphosphatase
- Glucose-6-phosphatase
Which hormones will function to stimulate gluconeogenesis? Through which enzymes does it exert this effect?
Glucagon
Cortisol
PEPCK
Fructose 1,6 bisphosphatase
Which hormone will function to decrease gluconeogenesis?
Insulin
Through PEPCK
Fructose 1,6 bisphosphatase
What molecule are excess lipids stored as?
Triglycerol
Under what conditions might a TAG store become utilised? How is this controlled?
Prolonged exercise
Stress
Starvation
Pregnancy
Hormonal control
Outline the structure of an adipocyte.
Large lipid droplet (mainly TAG and cholesterol ester)
Cytoplasm and organelles pushed to the side of the cell
How might adipocytes in an overweight individual differ to those in a healthy individual?
Upon weight gain, adipocytes increase in size before dividing to increase the total number of fat cells.
Which is the role of hormone sensitive lipase?
Mobilises TAG stores in adipose tissue, converting them to FA and glycerol.
FA is then transported by albumin to the tissues to be oxidised to produce energy.
Where does lipogenesis occur?
Liver
What is the major source of carbon used for lipogenesis?
Dietary glucose
What is the function of the malate shuttle in lipogenesis?
Production of NADPH, which is required by fatty acid synthase
What is the key regulatory enzyme in lipogenesis?
Acetyl-CoA carboxylase
What effect does insulin have on acetyl-CoA carboxylase?
Increases activity to increase lipogenesis following a meal.
In addition to insulin, what else will increase the activity of Acetyl-CoA carboxylase?
Citrate
What hormones and molecules will decrease the activity of Acetyl-CoA carboxylase?
Glucagon
Adrenaline
AMP
What is the substrate and product of the reaction catalysed by Acetyl-CoA carboxylase?
Acetyl Co A converted to Malonyl CoA
In fatty acid synthesis, what molecule are C2 atoms added as?
Malonyl CoA
Where does fatty acid synthesis occur?
Cytoplasm
How do glucagon and insulin mobilise TAG stored in adipose tissue?
Phosphorylate and activate hormone sensitive lipase, which converts TAG to glycerol and fatty acids which can travel by albumin to tissues to undergo beta oxidation.
How does insulin inhibit mobilisation of TAG stores in adipose tissue?
Insulin leads to de-phosphorylation and inhibition of hormone sensitive lipase.
What is the fate of glycerol produced when TAG is mobilised from adipose stores?
Travels to the liver and utilised as carbon source for gluconeogenesis.
What is the main difference in fuel stores in an obese man compared to a healthy man?
Significantly raised triacylglycerol levels
