S2 Glycogen and Fat as Energy Storage Flashcards
Which tissues have an absolute requirement for glucose as an energy source?
- Red blood cells
- Neutrophils
- Innermost cells of the kidney medulla
- Lens of the eye
What are the two main energy stores?
Glycogen and fat
What is glycogen stored in in skeletal muscles and the liver?
In granules
- in skeletal muscle glycogen is stored intramyofibrillar and intermyofibrillar
- in the liver stored in granules in the hepatocytes
What is the structure of glycogen?
It’s a branched polymer consisting of glucose residues.
Residues linked by alpha 1-4 glycosidic bonds and alpha 1-6 glycosidic bonds forming at branch points every 8-10 residues
What are the steps in glycogenesis?
- Glucose + ATP —> glucose-6-phosphate + ADP (hexokinase)
- Glucose-6-phosphate glucose-1-phosphate (phosphoglucomutase)
- Glucose-1-phosphate + UTP + H20 —> UDP-glucose + PPi (G1P uridyltransferase)
- Glycogen(n residues) + UDP-glucose —> glycogen(n+1 residues) + UDP (glycogen synthase and branching enzyme)
What is the difference between glycogen synthase and branching enzyme?
Glycogen synthase - alpha 1-4 glycosidic bonds
Branching enzyme - alpha 1-6 glycosidic bonds
Does the synthesis of glycogen require energy?
Yes
What are the two steps in glycogenolysis?
- Glycogen(n residues) + Pi —> glucose-1-phosphate + glycogen(n-1 residues) (glycogen phosphorylase or de-branching enzyme)
- Glucose-1-phosphate glucose-6-phosphate (phosphoglucomutase)
What happens to the glucose-6-phosphate in glycogenolysis? (In skeletal muscles and liver)
- muscle - goes into glycolysis - used by muscles for energy production
- liver - goes on to produce glucose - released by the liver into the blood for use by other tissues
What enzyme does the liver have that converts glucose-6-phosphate into glucose?
Glucose-6-phosphatase
How is liver glycogen metabolism regulated?
- glucagon and adrenaline phosphorylate glycogen synthase leading to a decrease in enzyme activity and glycogen phosphorylase increasing its activity
- insulin de-phosphorylates glycogen synthase and increases its activity and glycogen phosphorylase to decrease the enzyme activity
What is an allosteric activator of glycogen phosphorylase in muscles?
AMP
What is gluconeogenesis? Where does it occur? What are the main precursors?
When glycogen stores start to deplete alternative sources of glucose is required.
The liver (and a little in the kidney cortex)
Lactate, glycerol and amino acids
What are the 3 key enzymes in gluconeogenesis?
Why are these the key enzymes?
- Phosphoenolpyruvate carboxykinase (PEPCK) - Oxaloacetate to phosphoenolpyruvate
- Fructose-1,6-bisphosphatase- fructose-1,6-bisphosphate to fructose-6-phosphate
- Glucose-6-phosphatase- glucose-6-phosphate to glucose
These are the enzymes involved in the irreversible reactions
How and why is gluconeogenesis regulated?
PEPCK and fructose-1,6-bisphosphate are regulated by hormones in response to starving/fasting, prolonged exercise and stress.
Glucagon and Cortisol stimulate PEPCK and F-1,6-BP
Insulin inhibits PEPCK and F-1,6-BP
What is the time course for glucose utilisation?
- Glucose from food is utilised in 2 hours
- Glucose from glycogenolysis is utilised up to 8-10 hours
- Glucose from gluconeogenesis is utilised from 8-10 hours onwards
Which storage of energy is better, triacylglycerol or glycogen?
Triacylglycerol because it store more energy per gram
Are TAGs hydrophobic or hydrophilic? What does this mean for its storage?
Hydrophobic
Stored in an anhydrous form in adipose tissue
What type of regulation controls storage and mobilisation of TAGs?
Hormonal control
What are the steps in triacylglycerol metabolism?
- TAG is broken down by pancreatic lipase into fatty acids and glycerol in the s. intestine
- The fatty acids and glycerol are transported into the intestinal epithelial cell and are then packaged into a chylomicron
- The chylomicrons are transported into the lymph and into the blood (enters blood stream through left subclavian vein)
- In the blood, the TAG either goes straight to tissues or to adipose tissue. It is stored in adipose tissue where activation, by glucagon and adrenaline, of hormone sensitive lipase causes the transport of fatty acids from the breakdown of TAG in the adipose with albumin occurs to the tissues. At the tissues TAG is mobilised and fatty acid oxidation occurs which releases energy
What is lipogenesis? Where does it mainly occur?
Fatty acid synthesis
In the liver
What are the stages of lipogenesis?
- Glycolysis occurs producing pyruvate which enters the mitochondria
- In the mitochondria, pyruvate forms acetyl-CoA, oxaloacetate which then goes on to form citrate
- The cent rate is transported to the cytoplasm where it is cleaved to reproduce acetyl-CoA and oxaloaceteate
- Acetyl-CoA carboxylase produced malonyl-CoA from acetyl-CoA
- Fatty acid synthase complex builds the fatty acid by sequential addition of 2 carbon units provided by malonyl-CoA (carbon dioxide is lost)
- The fatty acid and glycerol-3-P form TAG and the TAG is transported by VLDL
What is lipolysis?
Fat mobilisation
Glucagon and adrenaline activate hormone sensitive lipase by phosphorylation
Insulin inhibits hormone sensitive lipase by de-phosphorylation
Hormone sensitive lipase breaks down TAG releasing glycerol and free fatty acid into the blood
The fatty acid undergoes beta oxidation and the glycerol is utilised in the liver for gluconeogenesis
Where does fatty acid oxidation and fatty acid synthesis occur?
Oxidation - in the mitochondria
Synthesis - in the cytoplasm
What coenzymes do fatty acid oxidation and synthesis require?
Oxidation - NAD+ and FADH (oxidative)
Synthesis - NADPH (reductive)
