Lecture 1: Carbohydrates Flashcards
What happens when the body is fed? Draw a diagram.
When a person is fed, there are changes in blood glucose concentration and insulin concentration.
• Hepatic glucose output falls when oral uptake is detected. It can even be fully suppressed.
• Insulin concentration increases.
• In muscle, insulin leads to a switch from glucose metabolism to glycogenesis. GLUT4 is used for glucose uptake.
• In liver, glycogenesis occurs. Glycogen synthase is upregulated, and glycogen phosphorylase is downregulated. GNG is not turned off since muscle and adipose tissue switch to anaerobic metabolism. Lactate, alanine and glycerol can be used for GNG, but the products are diverted into liver glycogen.
• In adipose tissue, insulin stimulates GLUT4. Glycolysis is activated. There is a switch from mobilisation to storage. G3P and FA are generated for esterification.
What happens in post-absorptive state?
The post absorptive state is when the body is not fed, but not starving either.
• Lactate normally comes from the RBCs and kidney medulla, unless the person is exercising.
• There is a 50:50 split between GNG and glycogenolysis.
• Glucagon only acts on the liver.
How does gluconeogenesis work?
- In the liver, alanine, lactate and glycerol all feed into the same metabolic network, which ends with the production of glucose.
- In adipose tissue, TAGs are broken down into glycerol. The glycerol is then moved to the liver.
- In kidneys, glutamine is converted into α-KG. GNG can then occur in order to form glucose which can be exported.
- In skeletal muscle, there are multiple pathways. Glycogenolysis occurs to form glucose. Glucose can then be broken down into alanine.
- Muscle protein can be broken down into amino acids. They can then be broken down into 2-oxo acids and then put into the TCA cycle.
- Glutamine is created from α-KG and then transported to the kidneys. α-KG comes from amino acid reactions, not the TCA cycle.
How is pyruvate carboxylase controlled?
Pyruvate carboxylase converts pyruvate into oxaloacetate.
• It is allosterically activated by acetyl-CoA in the liver.
• Acetyl-CoA is synthesised from fatty acids.
• FA mobilisation is stimulated by a decrease in insulin. HSL activity increases.
How is PEPCK controlled? Draw a diagram of glucagon and insulin control.
PEPCK is PEP carboxykinase, it converts oxaloacetate into PEP.
• It is transcriptionally regulated.
• cAMP concentration increases 10-fold in response to glucagon.
How are FBP/PFK controlled?
FBP and PFK are controlled in a bicyclic cascade.
• Glucagon drives gluconeogenesis.
• Insulin drives glycolysis.
How does glycogen metabolism work? Draw a diagram of liver and muscle glycogen metabolism.
Glycogen metabolism is controlled by insulin and glucagon.
• In the muscle, enzymes are regulated by AMP and ATP. AMP is produced during low glucose conditions.
• In the liver, glucose kinase is regulated by glucokinase regulatory protein (GKRP). During low glucose concentrations, GRKP binds to GK and inhibits it. GK goes to the nucleus.
• In high glucose concentrations, GKRP dissociates and GK goes to the cytoplasm.
How does PP1 function and how is it controlled?
Glycogen metabolism is controlled hormonally with insulin and glucagon.
• PP1 is activated by glucagon.
• The catalytic subunit can be bound by G subunits GL is found in the liver and GM is found in the muscle.
• GL is under transcriptional control of insulin and glucagon. It’s activated by insulin (probably by FOXO1).
• PP1 deactivates glycogen phosphorylase, but only when glucose is bound to phosphorylase. This only happens in the liver.
• PP1 deactivates all the phosphorylase first. There is 10 times as much phosphorylase as PP1. It must deactivate all phosphorylase before moving onto synthase.
• Reflection of the fact that liver is responding to the fed state of the whole body.
• Example of transcriptional, covalent and allosteric regulation.
