Module 8 Flashcards
regulation of metabolism
What is the purpose for cell communication
Survival, divide, differentiate
Explain the different cell signals may be sent
contact-dependent, paracrine, synaptic, endocrine
Describe some general characteristics of cell signalling pathways
extracellular signal will bind to a receptor protein, this send intracellular signaling proteins and then to effector proteins which produce metabolic enzyme, gene regulatory protein, cytoskeletal protein
Define and explain the characteristics of a molecular switch
Signals by phosphorylation, off when phosphate group leaves, uses ATP. Signalling by GTP-Binding, Signals when GTP present, stops when GDP is left
Explain the components of a G protein-coupled receptor signalling pathway, including how the members interact and how the intracellular signal is transmitted
Ligand binding to receptor activates intracellular GTP-binding protein, regulates an enzyme that generates an intracellular second messenger
What is metabolic enzyme for
altered metabolism
What is gene regulartory protein for
altered gene expression
What is cytoskeletal protein for
altered cell shap or movement
What is contact dependent signal
membrane bound signal molecule
What is paracrine signalling
local mediator sent to signalling cell which sends signals to target cells
What is Synaptic signalling
Neuron sending neurotransmitter through axon between the synapse
What is endocrine signalling
Transmit hormone through blood to a receptor of the target cell.
What are the general characteristics of signalling pathways
Specificity(specific binding site), amplification (molecules increase geometrically in an enzyme cascade), modularity(multivalent affinities form diverse signaling complexes from interchangeable parts). reversible points`
Does extracellular signalling molecules usually express fast
Yes, degrade fast as well, signal is transient
Example of signalling effect
Contraction of muscle, decrease rate and force of muscle contraction in heart cells, secretion of salivar in salivary gland
components of a G protein-coupled receptor signalling pathway
inactive receptor, inactive G protein, inactive enzyme
how the members interact and how the intracellular signal is transmitted in G protein coupled receptor
It only activate when GTP is coupled with it, then it will attach it to enzyme which sends another signal
Define a Receptor tyrosine kinase
A receptor is only activate when both domain are bound to phosphate
Explain activation of the insulin receptor and its intracellular signals
insulin receptor activates when insulin is present, transmit ERK to cells needed for cell division
Explain the mechanistic basis of why allosteric enzymes exhibit a sigmoidal substrate dependence.
combination of two michealis-menton curves, same Vmax, different Km values. Equilibrium shifts T to R as substrate binding stabilizes R-state
Describe how stabilization of the T and R state of allosteric enzymes changes their activity
R-state more active, therefore binding to substrate as it converts from T to R. because it was activated by the substrate
Recurring Motifs in Regulation
(1) Compartmentalization–where do the reactions occur? (cytosol, mitochondria, etc.)
(2) Allosteric regulation–enzymes catalyzing committed and usually irreversible steps (3) Specialization of organs–we will compare the metabolism of brain, liver, muscle & adipose
Hormonal regulation
(4) Covalent regulation
(5) Enzyme levels
What reaction happens in cytosol
Glycolysis, glycogenolysis, glycogenesis, pentose phosphate pathway(PPP)
What reaction happens in ER?
gluconeogenesis (in cytosol and mitochondria as well)
What reaction happens in mitochondria
E- transport chain,
What is the definition of allosteric
involving a change in the shape and activity of an enzyme that results from the binding of a regulatory molecule at a site other than the active site
Describe the allosteric regulation of PFK-1, including a description of the enzyme quaternary structure, substrate(s), product(s), inhibitor(s) and/or activator(s) involved.
4 subunit, substrate turn to R state when activators ADP, AMP are present. T state when inhibitor ATP, citrate are present. fructose 6-phosphate is the substrate, product is fructose 1,6-bisphosphate
Rationalize the allosteric regulation of other metabolic enzymes, including hexokinase and pyruvate kinase.
inhibited by the product of the reaction it catalyses
Compare the major fuel sources, energy stores and metabolism for the following tissues: brain
(1) Fuel sources:-Glucoseis major fuel for the human brain
(2) Fuel stores:-Brain lacks fuel stores ∴ relies on a constant supply of blood glucose (via GLUT3, KM ≈ 1.0 mM)
(3) Resting Conditions:-Brain consumes 60% of total GNG glucose = 120 g/day(1.76 MJ) in the resting state.
Compare the major fuel sources, energy stores and metabolism for the following tissues: skeletal muscle
(1) Fuel sources:-Glucose, fatty acids & ketone bodies.
(2) Fuel stores:-Muscle stores 75% of total body glycogen (> 5 MJ) and can represent 1% of muscle weight after a meal (other 25% stored in liver).(3) Resting Conditions:-Muscle utilizes fatty acids (Fas) as the major fuel in the resting state (85% of energy). Heart muscle uses the one of the ketone bodies, acetoacetate, in preference to glucose.
(4) Muscle & Liver metabolites connected by the CoriCycle
Compare the major fuel sources, energy stores and metabolism for the following tissues: adipose
(1) Fuel sources:- Requires glucose to perform major task of synthesizing and storing triacylglycerol, which is mobilized during fasting.
(2) Fuel stores:-In a 70 kg person, adipose stores >80% of total available energy (565 MJ or 15 kg).
(3) Resting Conditions:-Highly active during starvation (↓ insulin activates hormone sensitive lipase which breaks down TAG -see opposite
Compare the major fuel sources, energy stores and metabolism for the following tissues: liver
(1) Fuel sources:- Can utilize glucose, fatty acids, ketone bodies and amino acids. But prefers α-keto acidsderived from the degradation of amino acids in preference to glucose.
(2) Fuel stores:-Liver stores ¼ of total body glycogen. Uses lactate & alanine from muscle, glycerol from adipose & glucogenic amino acids from diet to make ∼ 200 gof glucose per day via gluconeogenesis. (
3) Resting Conditions:-Highly active during starvation making glucosevia GNG to maintain blood [glucose] primarily for the brain & RBCs. Also oxidizes FAs for energy and formation of KBs for the brain, heart muscle & other tissues.
(4) Other Functions:-Synthesizes TAGs, PLs & cholesterol & secretes as VLDL for lipoprotein transport & synthesizes heme. AN ALTRUISTIC ORGAN
effect of glucagon on metabolic pathways
- Drop in blood glucose below 4.5 mMtriggers glucagon release from the pancreas: resting [glucose]blood = 5.0 mM
- Glucagon causes an increasein blood glucose levels
- Glucagon activatesgluconeogenesis (GNG) & glycogenolysis (GGL) in the liver
- Glucagon inhibits glycolysis (GL) and glycogenesis (GG)
Explain the basis of the tissue distribution of glucose transporters GLUT1-4, in terms of priority tissues and Kt values
GLUT 1, Synthesized in the α cells of the pancreas
• Secreted into the blood when [glucose]blood drops < 4.5 mM kt = 3
GLUT 2, =17
GLUT 3 = 1.4
GLUT 4 Kt = 5
the effect of adrenaline on metabolic pathways
Involved in the fright-flight-fight response largely targeting muscle, but also hits liver cells
key players in the adrenaline signaling pathway
Catecholamine released from the adrenal gland
roles of each of the key players in adrenaline signalling
Synthesized from tyrosine
cAMP dependent kinase & everything downstream are also switched on by adrenaline binding to the β-adrenergic receptor, but hepatocytes are more responsive to glucagon.
Describe the fright-flight-fight response in muscle and how adrenaline signaling differs in muscle as compared to liver
• In Liver:Adrenaline switches on gluconeogenesis &
glycogenolysis
• In Muscle:-Adrenaline switches on glycolysis and glycogenolysis, create pyruvate to prolong TCA cycle to create ATP
how neuronal signaling reinforces the metabolic affects of adrenaline signaling
Ca2+ release stimulates glycogenolysis
Rationalize the effect of insulin on metabolic pathways
allow GLUT4 to membrane (in muscle & adipose)
allow Glycogen synthesis (in liver & muscle
stops glycogen breakdown (in liver)
Describe the structure of prepro-insulin, pro-insulin and insulin and the processes that generate the mature hormone.
Prepro-insuline is where signal sequence is attached to Cpeptide.
Pro-insulin is were C peptide is still present
Mature peptide is where Cpeptide is removed
List the key players in the insulin signaling pathway.
(3) Insulin Receptor Substrate-1 (IRS-1) & (4) Phosphatidylinositol 3,4,5 triphosphate (PIP3)
Explain why Acetyl-CoA is such an important metabolic intermediate
Because alcohol, aa, fatty acids and carbs uses it to form
