Coordinating Metabolism - Fuel Mobilisation Flashcards
describe fuel mobilisation
An important part of metabolic homeostasis is the body’s ability to rapidly convert stored macronutrients into usable energy.
This is required to meet its energy demands during periods of fasting, stress and activity
- for carbohydrates, the process of glycogenolysis is activated to obtain glucose for glycolysis
- for fats, lipolysis is activated to obtain FFAs for beta-oxidation
- for proteins proteolysis to obtain amino acids for energy
These processes are controlled by the hormones, glucagon and adrenaline with some tissue specificity.
how/where is glucagon produced?
Glucagon is produced in pancreatic alpha cells.
Comes from the proglucagon gene, alpha cells cut out the glucagon gene.
describe glucagon
Peptide hormone is secreted by pancreatic alpha cells
Secretion is stimulated by:
- fasting and starvation
- low blood glucose
- amino acids
- excersise (particularly prolonged or intense)
- stress via adrenaline
Activates processes that increase blood glucose
Used to treat hypoglycemic coma in type 1 diabetics and plays a prominent role in type 2 diabetes.
how does low glucose promote glucagon secretion?
- insulin from beta cells inhibits alpha cells
- high glucose (GLP-1) in the blood vessels inhibits alpha cells
- low glucose in blood vessels stimulates alpha cells
describe adrenaline
- adrenaline (epinephrine) is a hormone and a neurotransmitter
- synthesised from tyrosine in adrenal glands
- released on physical or psychological stress perceived by the hypothalamus and signalled to adrenals via the sympathetic nervous system
- primes the body for ‘fight or flight response’ ie. increases heart rate, bronchodilation, redirects blood flow to muscles and increases blood sugar
- release also triggers by low blood sugar and intense exersise
describe the summary diagram of the opposing effects of insulin and glucagon
High blood sugar:
- promotes insulin release
- insulin stimulates glucose uptake from blood
- into the tissue cells
- also stimulates glycogen reformation in the liver
- lowers blood sugar
Low blood sugar:
- promotes glucagon release
- glucagon stimulates glycogen breakdown in the liver and into the blood
- raises blood sugar
describe glucagon (and adrenaline) signalling via GPCRs
- glucagon receptors (on liver) and adrenaline receptors (on liver and muscle) have similar effect
- both hormones bing GPCR
- binding induces a conformational change that activates the G-protein
- activated G protein subunit activates adenylyl cyclase enzyme
- increases cAMP levels (secondary messenger)
- cAMP activates PKA via allosteric activation
- PKA activity can activate or inhibit downstream enzymes
Inhibits - Anabolic processes: glycogen synthesis via glycogen synthase
Activates - Catabolic processes: glycogen breakdown via glycogen phosphorylase
how does glycogen mobilisation (glycogenolysis) actually work?
glucagon or adrenaline binds to the receptor, GPCR changes shape, activates adenylate cyclase, then protein kinase A (PKA), which makes signal transduction occur throughout the cell.
end up with phosphorylase kinase phosphorylating glycogen phosphorylase, activating glycogen degradation.
glycogen degradation occurs by hydrolysis of the end glucose molecules and putting a phosphate on it to make glucose-1-phosphate
describe the mobilisation of glycogen to glucose in the liver
When you get to glucose-6-phosphate muscle doesn’t have glucose-6-phosphatase so this is why it can’t mobilise glucose Into the circulation, so glucose in the muscle can only be used by the muscle cells. whereas in the liver this pathway is complete and glucose can be put into the circulation.
Glycogen -> glucose-1-phosphate vis a phosphorylase enzyme
G-1-P <–> glucose-6-phosphate via a mutase enzyme
G-6-P -> glucose bia glycose-6-phosphatase
describe GPCR signaling downregualtion
Signalling pathways once stimulates have to be reset to respond to future signals
- ligands diffuse away from receptor
- intrinsic GTPase activity in the activated Gs subunit of the G protein converts it back to the inactive (GDP-bound) state.
- cAMP secondary messenger is metabolised by phosphodiester enzyme (PDE)
- PDE is inhibited by caffein hence its stimulatory action
- phosphates remove phosphate groups on phosphorylated proteins
how do we maintain out blood glucose levels over time from fasting?
About 100g of glycogen in liver but brain needs about 120g glucose per day. Gluconeogenesis can add between 80-100g/day
Where is the rest of the energy needed coming from for other tissues?
fat stores, these can provide energy for a very long time
describe how lipolysis in adipose is also activated via glucagon (and adrenaline) signalling
- GPCR that these bind to, making a signal transduction that activates protein kinase A (PKA)
- in this case the activated PKA phosphorylates and activates hormone sensitive lipase which hydrolyses the TAGs in fat droplets
- the released FFAs are bound to albumin and transported to tissues
- the released glycerol can be used to make new glucose in the liver
how does glucagon also stimulate beta-oxidation?
- upregulates the transcription of genes required for beta-oxidation ie. carnation acetyltransferases
- down regulates DNL ie. the synthesis of new FFAs (bc we want to use this for energy rather than fat storage)
what are the protein stores in our body used for?
- 10-15kg protein in body
- BOT no specific storage proteins
- some protein must be degraded to make amino acids to make glucose
- loss of too much protein causes structural and functional damage
- protein must be conserved as much as possible
what are the two types of generation of ATP in excersising muscle?
Aerobic excersise (requires 02, low intensity, prolonged)
- glucose from blood (or from glycogen as glucose-6-P) undergoes oxidative metabolism as does fatty acids (blood supplies fuels, blood supplies O2, active CAC, electron transport chai oxidative phosphorylation)
Anaerobic excersise (doesn’t require O2, high intensity for short periods)
- glycogen to glucose-6-P and anaerobic glycolysis
- phosphocreatine
