Lecture 33 - Coordinating Metabolism: Fuel Mobilisation Flashcards
What is the fuel mobilisation process for carbohydrates?
Glycogenolysis to obtain glucose for glycolysis
What is the fuel mobilisation process for fats?
Lipolysis to obtain FAs for beta-oxidation
What is the fuel mobilisation process for proteins?
Proteolysis to obtain amino acids for energy
What are the fuel mobilisation processes controlled by?
Hormones - Glucagon and Adrenaline
What is proglucagon?
A polypeptide precursor that gives rise to glucagon in pancreatic alpha cells and GLP-1 in L-cell and brain
(E.g. of different processing pathways in different cells)
What is glucagon?
A peptide hormone secreted by pancreatic alpha-cells
What is glucagon secretion stimulated by?
Fasting and starvation, low blood glucose, amino acids, exercise and stress (adrenaline)
What does glucagon do?
Stimulates liver to activate processes that increase blood glucose
Make glucose from non-carboyhrate sources e.g glycerol and amino acids (gluconeogenesis)
Breakdown of glycogen in the liver to glucose (glycogenolysis)
What is adrenaline?
A hormone and neurotransmitter synthesised from tyrosine in the adrenal gland
When is adrenaline released?
During physical or psychological stress perceived by the hypothalamus which signals to the adrenal gland
How does the hypothalamus signal to the adrenal gland?
Via the sympathetic nervous system
What does adrenaline do?
Stimulates liver and muscle to activate processes that increase blood glucose
What do adrenaline and glucagon bind to?
G-protein coupled receptors that cause a conformation change, activating the G-protein
What do the activated G-proteins do?
Activate adenylyl cyclase enzyme
What does adenylyl cyclase do?
Increase cAMP levels which activates protein kinase A (PKA) via allosteric activation
What does PKA do?
The activity of PKA can activate (catabolic processes) or inhibit downstream (anabolic processes) enzymes
When are g-proteins active?
When there is a GTP bound
When are g-proteins inactive?
When there is a GDP bound
What is the name of glycogen mobilisation?
Glycogenolysis
What is glycogen converted to via glycogen phosphorylase?
Glucose-1-Phosphate via hydolysis
What is Glucose-1-Phosphate converted to via mutase?
Glucose-6-Phosphate
What is missing in muscle cells?
Glucose-6-Phosphatase
What cells have Glucose-6-Phosphatase
Liver cells
What is Glucose-6-Phosphate used for in muscle cells?
Glycolysis only, as missing glucose-6-phosphotase
What is Glucose-6-Phosphate used for in liver cells?
Glucose via glucose-6-phosphatase
Signaling pathways once stimulated have be…?
reset to respond to future signals.
Ligands diffuse ____ from receptor
Away (down-regulates GPCR signalling)
What are the two mechanisms that can lead to g-protein downregulation?
Intrinsic GTPase and PDE
How does intrinsic GTPase work?
Intrinsic GTPase activity in the activated Gs subunit of the g-protein converts it back to the inactive state (GDP-bound)
What is cAMP secondary messenger metabolized by?
Phosphodiester enzyme (PDE).
PDE is inhibited by?
Caffeine
What do phosphatases do?
remove phosphate groups on phosphorylated proteins
How does lipolysis occur in adipose cells?
Through phosphorylation, PKA activates hormone-sensitive lipase which hydrolyses the TAGs in fat droplets to FFAs and then releases them bound to albumin to be transported to the tissues in the blood
What do adipocytes also release during lipolysis?
Glycerol and FFAs
What does the released glycerol from adipocytes do?
Is sent to the liver to be used to make new glucose
How does glucagon stimulate beta-oxidation?
Through up regulating of transcription of genes required for beta-oxidation and down-regulating DNL (synthesis of new fatty acids)
What can loss of too much protein cause?
Structural and functional damage, hence it must be as conserved as possible
How is ATP generated aerobically in exercising muscle?
Glucose from the blood or from glycogen (as G-6-P) undergoes oxidative metabolism and can enter the CAC
How is ATP generated anaerobically in exercising muscle?
Glycogen is converted to G6P and anaerobic glycolysis occurs. Phosphocreatine mobilised as well
What happens in anaerobic glycolysis?
Muscle glycogen is the source of fuel, O2 is not required, ATP is generated by a SLP and pyruvate is reduced to lactate to generate NAD+.
What does lactate cause?
Muscle pH to drop, thus fatigue
What is phosphocreatine?
An energy buffer made from gly, arg and met. A high-energy phosphate compound where phosphate can be transferred to ADP to make ATP. 20um per gram of muscle provides ~10s worth of ATP
What does exercise do in relation to creatine?
Uses phosphocreatine to create creatine
What does recovery do in relation to creaine?
Uses creatine to create phosphocreatine
