Adrenalin and signalling differences Flashcards
What type of regulation is Adrenalin?
Hormonal regulation
How does hormonal regulation work?
Bind on the outside and send signals into the cell. They change outputs through covalent modification of proteins
What are the key steps in signal transduction?
Signal transduction cascades mediate the sensing and processing of stimuli.
The signal goes to the reception which goes to transduction which leads to the cell response. One single event can lead to multiple outcomes.
How many protein kinases and protein phosphatases are coded in the human genome?
518 and 150 respectfully. 1000’s of auxiliary proteins are involved in the regulation of these.
What happens in the body during the fasting state?
Drop in blood glucose below 4.5 mM triggers glucagon
release from the pancreas: resting [glucose]blood = 5.0 mM
Glucagon causes an increase in blood glucose levels
Glucagon activates gluconeogenesis (GNG) & glycogenolysis
(GGL) in the liver
Glucagon inhibits glycolysis (GL) and glycogenesis (GG)
What is adrenaline?
Synthesized from tyrosine in 4 steps via dopamine intermediate. Catecholamine is released from the adrenal gland. Involved in the fright-flight-fight response
How does the adrenalin signaling pathway in the liver differ from the glucagon signaling pathway?
Adrenalin will bind the Adrenergic receptor (GPCR), causing the same initial pathway to occur to the production of cAMP. Protein kinase A and everything downstream is also switched on by adrenaline binding to the beta-adrenergic receptor - hepatocytes less receptive compared to glucagon pathway.
What is the fright-flight-fight response?
This is the adrenaline response in muscles
What happens during “Fright”?
Release of adrenaline from adrenal gland
What happens during “Fight and flight”?
Adrenaline stimulates glycogenolysis
and glycolysis in muscle so that ATP can be produced quickly for energy to “fly” away or “fight” with predator
How does adrenaline affect the muscle?
Adrenaline switches on glycolysis and glycogenolysis
What is the initial adrenaline signaling pathway?
epinephrine will bind the beta-adrenergic receptor, which will cause the dissociation of the bound G-protein. One of these subunits (Alpha) will bind GTP and become active. This will then interact with Adenylate cyclase, causing it to make cAMP from ATP. cAMP will then activate Protein kinase A, which can phosphorylate and activate phosphorylase kinase. This will convert phosphorylase b into phosphorylase a through phosphorylation.
How does signaling in muscle differ from liver: Glycolysis step 3
Phosphofructokinase-1 has a sequence at the N terminal (Serine) that can be phosphorylated to create Fructosebisphosphate-1. This can then lose the extra phosphate to go back and encourage the reaction to continue occurring. The muscle isozyme, however, does not contain this sequence at the N terminal, meaning it cannot be phosphorylated and so does not have the same N-terminal regulatory domain as the liver enzyme. This means it is not encouraged to continue occurring by FBPase-1, but through allosteric activation from the presence of the substrate, fructose-6-phosphate.
How does signaling in muscle differ from liver: Glycolysis step 10
cAMP dependant protein kinase phosphorylates the liver pyruvate kinase (L-PK) which inactivates the enzyme. This is done similarly to step three, with L-PK containing the needed Serine residue that can be phosphorylated. The muscle isozyme M-PK, instead has an arginine residue that cannot be phosphorylated, which reduces the need for hormonal regulation in muscle cells for glycolysis to occur.
How does signaling in muscle differ from liver: Only present in muscle
Muscles need a signal to indicate to them when to contract, and in these nerve cells exists an action potential. This action potential controls when the nerve cell releases Acetylcholine (ACh) into the synaptic cleft between the nerve and muscle cells. ACh then bind the ACh receptor on the muscle cell membrane, which activates the SR organelle and causes it to release Ca2+.
- This leads to two things; muscle contraction and the activation of a new metabolic pathway. This new pathway begins with Ca2+ activating phosphorylase kinase, which can phosphorylate glycogen phosphorylase, which will convert glycogen into G-1-P.
- Phosphorylase kinase has 4 subunits, alpha, beta. Gama, delta. The delta subunit is called the calmodulin domain, as this is the domain that can bind Ca2+. The beta subunit can also be phosphorylated. If either one of these happens, phosphorylase kinase will be partially activated, however, if both happen at the same time, the enzyme will become fully activated.
