Module 8

Question 1

What is the purpose for cell communication

Answer 1

Survival, divide, differentiate

Question 2

Explain the different cell signals may be sent

Answer 2

contact-dependent, paracrine, synaptic, endocrine

Question 3

Describe some general characteristics of cell signalling pathways

Answer 3

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

Question 4

Define and explain the characteristics of a molecular switch

Answer 4

Signals by phosphorylation, off when phosphate group leaves, uses ATP. Signalling by GTP-Binding, Signals when GTP present, stops when GDP is left

Question 5

Explain the components of a G protein-coupled receptor signalling pathway, including how the members interact and how the intracellular signal is transmitted

Answer 5

Ligand binding to receptor activates intracellular GTP-binding protein, regulates an enzyme that generates an intracellular second messenger

Question 6

What is metabolic enzyme for

Answer 6

altered metabolism

Question 7

What is gene regulartory protein for

Answer 7

altered gene expression

Question 8

What is cytoskeletal protein for

Answer 8

altered cell shap or movement

Question 9

What is contact dependent signal

Answer 9

membrane bound signal molecule

Question 10

What is paracrine signalling

Answer 10

local mediator sent to signalling cell which sends signals to target cells

Question 11

What is Synaptic signalling

Answer 11

Neuron sending neurotransmitter through axon between the synapse

Question 12

What is endocrine signalling

Answer 12

Transmit hormone through blood to a receptor of the target cell.

Question 13

What are the general characteristics of signalling pathways

Answer 13

Specificity(specific binding site), amplification (molecules increase geometrically in an enzyme cascade), modularity(multivalent affinities form diverse signaling complexes from interchangeable parts). reversible points`

Question 14

Does extracellular signalling molecules usually express fast

Answer 14

Yes, degrade fast as well, signal is transient

Question 15

Example of signalling effect

Answer 15

Contraction of muscle, decrease rate and force of muscle contraction in heart cells, secretion of salivar in salivary gland

Question 16

components of a G protein-coupled receptor signalling pathway

Answer 16

inactive receptor, inactive G protein, inactive enzyme

Question 17

how the members interact and how the intracellular signal is transmitted in G protein coupled receptor

Answer 17

It only activate when GTP is coupled with it, then it will attach it to enzyme which sends another signal

Question 18

Define a Receptor tyrosine kinase

Answer 18

A receptor is only activate when both domain are bound to phosphate

Question 19

Explain activation of the insulin receptor and its intracellular signals

Answer 19

insulin receptor activates when insulin is present, transmit ERK to cells needed for cell division

Question 20

Explain the mechanistic basis of why allosteric enzymes exhibit a sigmoidal substrate dependence.

Answer 20

combination of two michealis-menton curves, same Vmax, different Km values. Equilibrium shifts T to R as substrate binding stabilizes R-state

Question 21

Describe how stabilization of the T and R state of allosteric enzymes changes their activity

Answer 21

R-state more active, therefore binding to substrate as it converts from T to R. because it was activated by the substrate

Question 22

Recurring Motifs in Regulation

Answer 22

(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

Question 23

What reaction happens in cytosol

Answer 23

Glycolysis, glycogenolysis, glycogenesis, pentose phosphate pathway(PPP)

Question 24

What reaction happens in ER?

Answer 24

gluconeogenesis (in cytosol and mitochondria as well)

Question 25

What reaction happens in mitochondria

Answer 25

E- transport chain,

Question 26

What is the definition of allosteric

Answer 26

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

Question 27

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.

Answer 27

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

Question 28

Rationalize the allosteric regulation of other metabolic enzymes, including hexokinase and pyruvate kinase.

Answer 28

inhibited by the product of the reaction it catalyses

Question 29

Compare the major fuel sources, energy stores and metabolism for the following tissues: brain

Answer 29

(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.

Question 30

Compare the major fuel sources, energy stores and metabolism for the following tissues: skeletal muscle

Answer 30

(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

Question 31

Compare the major fuel sources, energy stores and metabolism for the following tissues: adipose

Answer 31

(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

Question 32

Compare the major fuel sources, energy stores and metabolism for the following tissues: liver

Answer 32

(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

Question 33

effect of glucagon on metabolic pathways

Answer 33

* 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)

Question 34

Explain the basis of the tissue distribution of glucose transporters GLUT1-4, in terms of priority tissues and Kt values

Answer 34

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

Question 35

the effect of adrenaline on metabolic pathways

Answer 35

Involved in the fright-flight-fight response largely targeting muscle, but also hits liver cells

Question 36

key players in the adrenaline signaling pathway

Answer 36

Catecholamine released from the adrenal gland

Question 37

roles of each of the key players in adrenaline signalling

Answer 37

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.

Question 38

Describe the fright-flight-fight response in muscle and how adrenaline signaling differs in muscle as compared to liver

Answer 38

• In Liver:Adrenaline switches on gluconeogenesis & glycogenolysis • In Muscle:-Adrenaline switches on glycolysis and glycogenolysis, create pyruvate to prolong TCA cycle to create ATP

Question 39

how neuronal signaling reinforces the metabolic affects of adrenaline signaling

Answer 39

Ca2+ release stimulates glycogenolysis

Question 40

Rationalize the effect of insulin on metabolic pathways

Answer 40

allow GLUT4 to membrane (in muscle & adipose) allow Glycogen synthesis (in liver & muscle stops glycogen breakdown (in liver)

Question 41

Describe the structure of prepro-insulin, pro-insulin and insulin and the processes that generate the mature hormone.

Answer 41

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

Question 42

List the key players in the insulin signaling pathway.

Answer 42

(3) Insulin Receptor Substrate-1 (IRS-1) & (4) Phosphatidylinositol 3,4,5 triphosphate (PIP3)

Question 43

Explain why Acetyl-CoA is such an important metabolic intermediate

Answer 43

Because alcohol, aa, fatty acids and carbs uses it to form