FBS Semester 2 Flashcards
Revision of semester 2 FBS I from the University of Adelaide
Describe the changes in the body following a meal (glucose levels, hormone release & storage)
Consumption of food –> increased blood glucose –> stimulation of insulin release from pancreatic beta cells of islet of Langerhans –> glycogenesis, protein production & fatty acids (stored in adipocytes).
Excess food is stored in adipocytes as triglycerides (TAGs) via lipogenesis
Describe the changes in the body following fasting (glucose levels, hormone release & storage)
Fasting –> decreased blood glucose levels –> decreased insulin secretion –> reduced inhibition of glucagon –> increased glucagon secretion from pancreatic alpha cells –> degradation of body stores (gluconeogenesis using liver glycogen, production of fatty acids and glycerol from adipose triglycerides
Describe the changes in the body following the fright, flight or fight response (glucose levels, hormone release & storage)
Adrenaline is released –> stimulating liver glycogen to undergo gluconeogenesis –> increased blood glucose
At the same time, adrenaline –> stimulation of adipocytes to release blood fatty acids
These actions allow muscles to have no shortage of fuel in life threatening situations.
What are the three major fuel depots in the body?
Liver: Glycogen storage (breaks down glycogen into glucose)
Adipose tissue: Triglyceride storage (breaks to fatty acids & glycerol)
Muscles: Stores glycogen, however is only used as a fuel depot when no more fats & glucose remain. The protein is converted into glucose.
Describe the mechanism of insulin action
Insulin binds to extracellular receptor tyrosine kinase cytoplasmic domain –> signal amplification via PIP3 secondary messenger –> activation of protein kinase B –> phosphorylation events –> Cellular response
Cellular response involves:
- Recruitment of insulin dependant GLUT4 glucose transporters –> increased glucose entering cell –> glyconeogenesis
- Increased amino acid uptake –> increased synthesis of new proteins
- Excess glucose & amino acids –> lipogenesis, storing them as fat in adipose tissue
What is glycogen & its function?
Glycogen is a highly branched polymer of glucose.
Function: to store and retrieve glucose quickly.
Why is glucose stored as glycogen? (Three reasons and why)
- Glycogen, made up of repeating units of glucose, is hence an efficient store
- It helps to reduce osmotic pressure. This is because glucose has OH- groups, and therefore has increased affinity for H2O. Glycogen has less OH- groups and therefore less affinity for H2O –> reduced osmotic pressure
- Storage of glucose as glycogen prevents hyperglycaemia –> reduced formation of advanced glycated end products (AGEs) and other disease states
What is glucokinase?
Glucokinase is an enzyme in the liver (isoenzyme in pancreas) that phosphorylates and traps glucose entering the liver via GLUT2, preventing hyperglycaemia. Glucose is stored as glycogen as a result, with excess stored as fat.
What are the counter regulatory hormones and how are they released?
Counter regulatory hormones: adrenaline, noradrenaline, cortisol, glucagon.
Mechanism of release:
Low blood glucose detected by regulatory centre of hypothalamus –> release of adrenocorticotropic hormone (ACTH) secreted by anterior pituitary –> stimulation of adrenal cortex to release cortisol.
Lower levels of blood glucose also cause increased sympathetic stimulation –> release of adrenaline and noradrenaline.
Also, lower levels of blood glucose is detected by the hypothalamus –> stimulation of pancreas to release glucagon from alpha cells of islet of Langerhans
Describe the mechanism of glucagon action (binding to receptor and general cellular effects)
Glucagon binds to extracellular G-protein coupled receptor –> signal transduction effects –> activation of cAMP –> allosteric activation of Protein Kinase A (PKA) –> phosphorylation events –> activation of enzymes in catabolic pathways (liver glycogenolysis enzymes, adipocyte lipolysis enzymes) & inactivation of enzymes in anabolic pathways.
Describe the mechanism of liver glycogenolysis
Glucagon binds to GPCR –> activation of 2ndary messenger cAMP –> allosteric activation of PKA –> phosphorylation events –> activation of glycogen phosphorylase –> phosphorylation of glycogen to glucose-1-P –> conversion of glucose-1-P to glucose-6-P via glycogen phosphorylase –> glucose-6-P converted to glycose via glucose-6-phosphatase (enzyme found only in the liver. Removes phosphate for use again with glycogen phosphorylase) –> glucose released into the blood
The main purpose of glycogenolysis is to maintain homeostasis of blood glucose levels and prevent hypoglycaemia.
Describe the mechanism of adrenaline binding (binding to receptor and general cellular effects)
Adrenaline binds to GCPR –> signal transduction effects –> activation of cAMP secondary messenger –> allosteric activation of Protein Kinase A –> phophorylation events –> activation of catabolic enzymes & deactivation of anabolic enzymes.
Note: liver glycogenolysis also increases when adrenaline levels are raised
Describe the mechanism of muscle glyconeogenesis
Adrenaline binds to GPCR –> activation of secondary messenger cAMP –> allosteric activation of PKA –> phosphorylation events –> activation of glycogen phosphorylase within muscle cells –> glucose phosphorylase facilitates conversion of glycogen to glucose-1-P –> glucose-1-P is converted to glucose-6-P via glycogen phosphorylase –> glucose-6-P utilised to create ATP for energy via glycolysis.
What is Von Gierke’s disease? Give reasons for the large abdomen seen in patients with this disease.
A disease involving mutation in the gene coding for glucose-6-phosphatase. The mutation results in a deficiency of glucose-6-phosphatase, causing hypoglycaemia between meals.
The large abdomen occurs as there is a deficiency in glucose-6-phosphatase. This results in the accumulation of glucose-6-P (normally converted to glucose by glucose-6-P within the liver), leading to increased osmotic pressure. The increased osmotic pressure causes net movement of water into the cell giving rise to an enlarged liver and therefore abdomen.
What is McCardle’s disease? Give reasons for the muscle cramps experienced by patients with this disease.
McCardle’s Disease refers to the absence of glucose-phosphorylase in muscle cells. This causes patients to have painful muscle cramps and the inability to perform strenuous exercise.
The muscle cramps occur as the lack of RDE (glucose-phosphorylase) prevents the conversion of glycogen into glucose-1-P to in turn be turned into glucose-6-P. Consequently, there is insufficient glucose-6-P to produced ATP for muscles.
