Which tissues have an absolute requirement for glucose as an energy source?
- Red blood cells
- Innermost cells of kidney medulla
- Lens of the eye
Why are stable blood glucose levels important?
How is this done?
- Essential for normal brain function
- Glycogen stores glucose to enable blood glucose to be kept at required levels
How is glycogen stored?
Glycogen is stored as granules
Where is glycogen stored?
- Muscle glycogen – stored as granules in and between myofibrils
- Liver glycogen – stored as granules in hepatocyte
Describe the molecular structure of glycogen
- Glycogen is a polymer consisting of chains of glucose residues
- Glucose residues linked by α-1-4 glycosidic bonds with α-1-6 glycosidic bonds
Glycogenesis is the process of synthesising glycogen. It requires energy.
In four steps, describe this process
⇒ Glucose + ATP → Glucose 6-P + ADP (hexokinase/glucokinase)
⇒ Glucose 6-P → Glucose 1-P (phosphoglucomutase)
⇒ Glucose 1-P + UTP + H2O → UDP-Glucose + PPi
⇒ Glycogen(n residues) + UDP-Glucose → Glycogen(n + residues) + UDP (glycogen synthase / branching enzyme)
Glycogenolysis is the process of glycogen degradation.
In three steps, describe how this process is not a simple reversal of glycogenesis
⇒ Glycogen(n residues) + Pi → Glucose 1-P + Glycogen(n-1 residues) (glycogen phosphorylase / debranching enzyme)
⇒ Glucose 1-P → Glucose 6-P (phosphoglucomutase)
⇒ Glucose 6-P → released into blood as glucose (liver) / used for glycolysis (muscle)
Illustrate and explain how glycogen stores serve different functions in liver and muscle
- Liver: G6P converted to glucose and exported to blood (buffers blood glucose levels)
- Muscle: G6P enters glycolysis for energy production (no glucose-6-phosphatase)
Illustrate the relationship between glycogen synthesis and degradation
What are the rate limiting enzymes for glycogen metabolism?
- Glycogen synthesis – glycogen synthase
- Glycogen degradation – glycogen phosphorylase
Illustrate how the hormonal regulation of glucose metabolism occurs in a reciprocal fashion
Explain how the hormonal regulation of muscle glycogen stores differs from that of the liver
- Glucagon has no effect on muscle glycogen stores
- AMP is an allosteric activator of muscle glycogen phosphorylase but not of the liver form of enzyme
Glycogen storage diseases are inborn errors of metabolism (inherited diseases).
How do they occur?
Glycogen storage disease arise from deficiency or dysfunction of enzymes of glycogen metabolism
Describe three consequences of glycogen storage diseases
- Liver and/or muscle can be affected
- Excess glycogen storage can lead to tissue damage
- Diminished glycogen stores can lead to hypoglycaemia & poor exercise tolerance
Identify and describe two examples of glycogen storage diseases
- McArdle disease – muscle glycogen phosphorylase deficiency
- von Gierke's disease – glucose-6-phosphatase deficiency
What is gluconeogenesis and when does it occur?
- Gluconeogenesis is the production of new glucose
- Occurs beyond ~ 8 hours of fasting as liver glycogen stores start to deplete and an alternative source of glucose is require
Where does gluconeogenesis occur?
Occurs in liver and to lesser extent in kidney cortex
Identify and describe the three major precursors for gluconeogenesis
- Lactate – from anaerobic glycolysis in exercising muscle and red blood cells (Cori cycle)
- Glycerol – released from adipose tissue breakdown of triglycerides
- Amino acids – mainly alanine
Describe the Cori Cycle
Why can glucose not be synthesised from acetyl-CoA?
Acetyl-CoA cannot be converted into pyruvate as PDH reaction is irreversible so there is no net synthesis of glucose from acetyl-CoA
Identify the three key enzymes in gluconeogenesis
Steps 1 & 2 are the major control sites of pathway
Which enzymes are used in the hormonal regulation of gluconeogenesis?
- Phosphoenolpyruvate carboxykinase (PEPCK)
- Fructose 1,6-bisphosphatase
Gluconeogenesis is regulated by hormones in response to which physiological states?
- Prolonged exercise
Illustrate how the hormonal regulation of gluconeogenesis is dependent on the enzymes PEPCK and Fructose 1,6-bisphosphatase
Outline the time course of glucose utilisation
How and when are lipids stored?
- TAG is storaged when lipid intake is in excess of requirements
- TAGs are hydrophobic and therefore stored in an anhydrous form in adipose tissue
The storage & mobilisation of TAGs is under hormonal control.
When are TAGs utilised?
- Prolonged exercise
TAGs are stored in adipocytes in adipose tissue.
Describe the structure and contents of these cells
Provide a brief overview of dietary triacylglycerol metabolism
In six steps, outline the mechanism of lipogenesis
⇒ Glucose → pyruvate in cytoplasm (glycolysis)
⇒ Pyruvate enters mitochondria and forms acetyl-CoA & OAA
⇒ Acetyl-CoA and OAA condense to form citrate
⇒ Citrate enters cytoplasm and cleaved back Acetyl-CoA & OAA
⇒ Acetyl-CoA carboxylase produces malonyl-CoA from Acetyl-CoA
⇒ Fatty acid synthase complex builds fatty acids by sequential addition of 2C by malonyl-CoA