1008 - Hormonal Control of Metabolism Flashcards
What is the well-fed state?
Period in the hours immediately following a meal, characterised by a high insulin:glucagon ratio in response to higher blood [glucose]. Glucose and AAs enter bloodstream, lipids are packed into chylomicrons and enter blood via lymphatic system. As insulin promotes fuel storage, look at glycogenesis, fatty acid formation etc.
Adrenaline and glucocorticoids do not play major roles.
What is the fasting state?
Period from around 3-4 hours post-meal that can extend for 4-5 days. Characterised by low insulin secretion, and high glucagon release (reduced insulin:glucagon ratio compared to well-fed). Glycogenolysis occurs initially (early fasting), which then switches to gluconeogenesis in late fasting.
What is the starvation state?
Severe or prolonged deficiency in caloric energy, nutrient and vitamin intake. Characterised by lack of insulin and high [glucagon]. Low levels of gluconeogenesis (for the brain), with energy needs being met by FAs and ketone bodies. AAs are not broken down, so less urea produced and excreted.
What is the site of Production for (pro-)Insulin? What is the stimulus for release?
Pro-insulin produced in pancreatic β-cells (ER) and synthesised into insulin in Golgi bodies. Secreted in response to a rise in plasma glucose (via increased [ATP]).
What is the site of Production for glucagon? What is the stimulus for release?
Synthesised in pancreatic α-cells. Release signalled by low blood sugar (low ATP/ADP), elevated AAs (but much still to be learned.
What is the site of Production for adrenaline? What is the stimulus for release?
Produced in the adrenal medulla, released in response to activation of SY nervous system.
What is the site of Production for Cortisol? What is the stimulus for release?
Produced in the adrenal cortex, with a cholesterol backbone. Released in response to ACTH from the pituitary gland.
What are the biological effects of insulin?
Hormone of abundance that wants to drop blood glucose levels and promote energy storage. Therefore, activates GLUT transporters, glycogen synthase, and protein/lipid synthesis. Also fires up glycolysis as it’s still a method of dropping blood sugar, but inactivates other energy-mobilising enzymes.
Active in the well-fed state, where it impacts on carb metabolism. Minimised in fasting and absent in starvation state.
What are the biological effects of glucagon?
Hormone of fasting that wants to raise glucose levels. Works almost exclusively in the liver to stimulate glycogen-olysis. Once glycogen is low, stimulates gluco-neogenesis, and reduces glycolitic flux, with intermediates shunted to gluconeogenesis.
What are the biological effects of adrenaline?
Hormone for fight or flight that wants to mobilise energy. Acts to stimulate glycogenolysis (in both liver and muscle), and activates lipases (muscle and adipose) to mobilise fatty acids from TAGs and provide energy for muscles and liver.
What are the biological effects of cortisol?
Hormone for sustained stress. Stimulates gluconeogenesis (from amino acids) and glycogen storage in the liver. Mobilises amino acids from muscle, and fatty acids from TAGs.
What are the key enzymes targeted by insulin?
Glycogen Synthase (stimulate) and Glycogen phosphorylase (inhibit).
Also stimulate glucokinase and the GLUT transporters.
Stimulate many other enzymes on the glycogenic and glycolytic pathways - just want to get it away from being glucose.
Inhibit PEPCK
Stimulate Protein synthesis
Stimulate lipoprotein lipase, inhibit hormone-sensitive lipase
What are the key enzymes targeted by glucagon?
Glycogen phosphorylase (stimulate) and glycogen synthase (inhibit).
Inhibit F2,6bP and pyruvate kinase
Stimulate PEPCK and G-6-P
Effects almost exclusively in the liver.
What are the key enzymes targeted by adrenaline?
Glycogen phosphorylase (stimulate) and glycogen synthase (inhibit) in both liver and muscle.
Stimulate lipases in muscle and adipose tissue
Inhibit acetyl-CoA carboxylase.
What are the key enzymes targeted by cortisol?
Stimulate glycogen synthase, PEPCK, and AA catabolics.
Aim to mobilise energy from muscle and fat - stimulate protein catabolism and hormone-sensitive lipase.
