Endocrinology: Control of Metabolism Flashcards
Describe the action of insulin on metabolism in the liver, muscle and adipose tissue
- Water-soluble hormone: binds to extracellular tyrosine kinase receptors on the cell membrane
- Binding creates a cascade of events (signal amplification), that causes numerous phosphorylation events
- Recruitment/ translocation of insulin-dependent transporters that fuse with cell membrane (GLUT-4) from cytoplasm to the cell membrane in adipocytes and myocytes
- Glucose channels open, allowing glucose to enter the cell
- Insulin promotes uptake of glucose into muscle and adipose
- Insulin promotes fat and glycogen synthesis in the liver from acetyl-CoA
- Fat is sent to adipose tissue for storage
- Insulin secretion decreases during fasting
- Cellular responses lead to anabolic pathways activated (glycogen and fat synthesis), catabolic pathways inactivated (beta oxidation of fats, glycolysis)
Describe the action of glucagon on metabolism in the liver
- Glucagon stimulates liver to break down glycogen into its glucose subunits, through glycogenolysis
- Increases blood glucose levels, which goes through glycolysis into pyruvate, and then into acetyl-coA, which enters the Kreb’s cycle
- Glucagon promotes gluconeogenesis: synthesis of glucose from non-carbohydrate sources, e.g., amino acids (i.e., for the brain, needs glucose as an energy source)
- Promotes ketogenesis; fatty acids converted into ketone bodies, which act as an additional fuel source, for the brain, when glucose is limited
Describe the action of glucagon on metabolism in muscles
- Minimal direct effect
- Increase in blood glucose provides source of energy for muscle
Describe the action of glucagon on metabolism in adipose tissue
- Glucagon stimulates lipolysis = breakdown of triglycerides into glycerol and free fatty acids
- Fatty acids can be used as an alternative energy source (by muscles, not brain) when glucose levels are low
How can metabolic pathways in a cell be controlled?
- Pathways in the cytosol can be controlled by:
o Substrate (food) availability)
o Hormones
o Enzyme control
Covalent modification
Allosteric modification - At a gene level by inducing/ repressing:
o Transcription
o Translation
o Degradation
What happens in metabolic pathways is not controlled in a cell?
Metabolic mayhem
What is reversible covalent modification? How does it control enzyme activity?
- Formation of a covalent bond
- For example, phosphorylase is the enzyme that assists in the breakdown of glycogen to its glucose subunits
- Phosphorylase B (less active) is converted to phosphorylase A (active) through addition of a phosphate group
- Covalent modification does not control the LEVEL of enzyme activity; simply on or off
What is allosteric modification? How does it control enzyme activity?
- Allosteric activators or deactivators
- Activators turn enzymes on; bind to the allosteric binding site, and cause a conformational change in the active site of the enzyme, allowing substrates to be able to bind
- Deactivators turn enzymes off; bind to the allosteric site, causing a conformational change in the active site, meaning the substrate is no longer complementary and cannot bind
- Enzymes can be turned on/ off ‘to a certain degree’: control the LEVEL of enzyme activity
What is the energy source for the brain at 5 and 400 hours after not eating?
5 hours
- Glycogen from liver stores, via glycogenolysis (primary)
- Glucose from non-carbohydrate sources (amino acids), via gluconeogenesis
400 hours
- Glycogen stores depleted
- Gluconeogenesis can only provide a limited amount of glucose
- Primary energy source for the brain is ketone bodies; produced through ketogenesis in the liver (from fatty acids derived from adipose tissue triglycerides)
What are ketone bodies and why are they produced?
Ketone bodies are an alternative fuel source for the brain. They are produced in periods of fasting, as they are able to cross the blood-brain barrier to be used by the brain during periods where glucose is scarce, to enable function and survival.
Difference between water and fat soluble hormones
- Water soluble hormones cannot pass through the cell membrane (hydrophobic) and must first bind to a signal receptor in the membrane (e.g., insulin and glucagon). This activates a whole cascade
- Fat soluble hormones are hydrophobic and pass through the cell membrane and then bind to a signal receptor within the cytoplasm. Signals are amplified so not a lot of hormones need to enter cells
Action of insulin in terms of glucose uptake into myocytes/ adipose tissue
- Insulin binds to surface receptors, initiating cascade of intracellular signalling events
- Results in translocation of glucose transporter proteins (e.g., GLUT4) from intracellular storage vesicles to the cell membrane
- Embeds into the cell membrane and facilitates uptake of glucose into myocytes and adipose tissue from the bloodstream
What controls the release of glucagon in the pancreas?
- Low blood glucose levels trigger glucagon production and secretion from pancreatic alpha islet cells
- Amino acids can also stimulate glucagon release
- Adrenalin and noradrenaline can also stimulate release (sympathetic nervous system control)
- Hormonal regulation: insulin (from beta cells in pancreas) and somatostatin (from gamma cells in pancreas) inhibits glucagon secretion
What are the different types of diabetes mellitus?
Diabetes melltius: with sugar
- Type 1: lack of insulin
- Type 2: diminished effectiveness of insulin (insulin resistance – doesn’t have the same amplification effects when it binds to surface receptors)
- Type 2 is increasing in community: accounts for 85-90% diabetic cases, increase thought to be due to lifestyle (obesity, inactivity)
- Impact: 40% tissues have insulin dependent transporters
What is diabetes insipidus?
Diabetes insipidus: sugar free (decreased levels of anti-diuretic hormone
- Other types: gestational, congenital
