Signal Transduction

Question 1

What is signal tranduction

Answer 1

Way for signal from outside to affect function via amplification

Question 2

Flow chart of tranduction

Answer 2

Signal —– reception —- transuction —– response

Amplification from reception to transduction

Question 3

Epinephrine binds

Answer 3

7 transmembrane domain protein known as a G-protein coupled receptor

Question 4

G-protein coupled receptor that epinephrine binds to interacts with ____ and what does it do?

Answer 4

Heterotrimeric G protein that has 3 subunits

Will activate another enzyme

Question 5

Epinephrine signaling pathway

Answer 5

Epinephrine binds B adrenergic receptor…G-protein phorphorylated and loses beta and gamma subunits…GTP with alpha unit binds to adenylate cyclase…adenylate cyclase converts ATP to cyclic AMP….cyclic AMP activates protein kinase A…PKA then phosphorylates serine residues on target proteins

Question 6

Adenylate cyclase rxn

Answer 6

ATP —- cyclic AMP

Question 7

Cyclic AMP rxn

Answer 7

Protein Kinase A ——- activate protein Kinase A

Question 8

Protein kinase A regulated by (what mechanism)

Answer 8

Autoinhibition

Question 9

1st part of cAMP cascade termination

Answer 9

Epinephrine dissociates…bARK phosphorylates tail of receptor…this binds B-arrestin that blocks binding of new heterotrimeric proteins

Question 10

bARK name and function

Answer 10

Beta-adrenergic-receptor kinase

Phosphorylates receptor using ATP to allow recruitment of B-arrestin

Question 11

B-arrestin function

Answer 11

Blocks new heterotrimeric G-proteins from binding receptor

Question 12

Second part of cAMP termination

Answer 12

GTP associated G-protein with adenylate cyclase undergoes hydrolysis to make GDP…beta and gamma subunits return and molecule dissociates

Question 13

What happens to cyclic AMP during termination

Answer 13

Hydrolyzed by cyclic AMP phosphodiesterase to AMP

Question 14

Cholera enzyme rxn

Answer 14

Catalyzes ADP-ribosylkation of G-protein alpha subunit

Question 15

Cholera mechanism of disease

Answer 15

Internal GTPase is blocked and left in on state…overproduction of cAMP and PKA leads to membrane ion transport protein phosphorylation…loss of ions and water leads to diarrhea
Intestinal

Question 16

Pertussis rxn

Answer 16

ADP-ribosylation of the heterotrimeric subunit (which is inhibitory)

Question 17

Pertussis mechanism of disease

Answer 17

Blocks exchange of GTP for GDP and therefore heterotrimeric subunits with GDP remain off…adenylate cyclase, once on, is never turned off
Respiratory tract

Question 18

Enzyme-linked receptors

Answer 18

Transduce an external signal across membrane by generating intramolecular enzymatic activity

Question 19

Cytokine receptors

Answer 19

Receptor has NO intrinsic enzymatic activity and a second protein is activated by the binding of the cytokine or signaling agent

Question 20

Cytokine receptors often activated

Answer 20

Jak-STAT signaling

Question 21

Insulin receptor structure

Answer 21

Dimer with two extracellular alpha for binding pocket of insulin…each B subunit contains kinase omain

Question 22

Binding of insulin results in

Answer 22

Cross-phosphorylation and activation of the receptor

Question 23

Phosphorylated insulin receptor sites act as binding site ofor

Answer 23

IRS-1

Question 24

IRS-1 allows binding of

Answer 24

PI-3K

Question 25

PI-3K rxn

Answer 25

PIP2 ---- PIP 3

Question 26

PIP3 function

Answer 26

Activates PIP 3-dependent kinase

Question 27

PIP 3-dependent kinase function

Answer 27

phophorylates and activates kinases such as AKT

Question 28

Insulin pathway

Answer 28

Receptor phosphorlates IRS...IRS binds PI3K...PI3K converts PIP2 to PIP3 via phosphorylation...PIP3 activates Pip3 dependent kinase...PIP3 dependent kinase phosphorylates AKT to activate it

Question 29

insulin structures

Answer 29

Dimer linked by 2 disulfide

Question 30

Type 1/2 diabetes onset, age, body, ketoacidosis

Answer 30

1 - sudden, any age, thin or normal, common | 2 - gradual, adults, often obese, rare

Question 31

Type 1/2 diabetes autoantibodies, andogenous insulin, concordance in ID trwins, prev

Answer 31

1 - usually present, low or absent, 50%, less | 2 - Absent, Normal increased or decreased , 90%, more prevalent

Question 32

Type 1 diabetes symptoms

Answer 32

``` Polyuria Polydipsia Polyphagia Fatigue/weakness Irratability Blurred vision Increased yeast infections ```

Question 33

Characteristics of T1DM

Answer 33

Hyperglycemia caused by increased gluconeogenesis and insufficient glucose absorption Ketosis from accumulation of free fatty acids

Question 34

Underlying cause of T1DM

Answer 34

Autoimmune disorder leads to destruction of B cells in pancreas

Question 35

T2DM predominant cause

Answer 35

Obesity

Question 36

What happens in T2DM

Answer 36

Eat...food becomes glucose...pancreas secretes insulin...cells are resistant so glucose not absorbed...still feel hungry...eat again...hyperglycemic...hyperinsulinemic...eventual B cell death

Question 37

Metformin

Answer 37

Improves sensitivity of body tissues to insulin...also lowers glucose production in liver but not actual blood sugar

Question 38

Sulfonylureas

Answer 38

Increase insulin secretion

Question 39

Thiazolidinediones

Answer 39

Increase insulin sensitivity but have risks

Question 40

Adipokines

Answer 40

Cytokines secreted by adipose tissue

Question 41

Leptin function

Answer 41

Tells brain how much body fat you have (or how much energy storage you have)

Question 42

What happens to leptin after a few days of overeating?

Answer 42

Sets new baseline level as very hig h

Question 43

Leptin acts on what in brain?

Answer 43

Hypothalamus

Question 44

Insulin effect on leptin

Answer 44

Increases secretion

Question 45

Leptin effect on sinulin

Answer 45

Reduce secretion and gene expression

Question 46

How does leptin signal reach insulin

Answer 46

Directly from leptin on B cells | Via autonomic nervous system

Question 47

Leptin effect on pancres

Answer 47

Increase B cell proliferation

Question 48

Leptin signaling

Answer 48

Leptin binds to receptor, resulting in Jak-Kinases cross-phosphorylating tyrosine residues...STATs dock on tyrosines and are phosphorylated by JAK enzymes...STAT travels to nucleus to affect gene transcription

Question 49

Effect of STAT in nucleus

Answer 49

Decreased appetite and increased energy expenditure

Question 50

Leptin insensitivity

Answer 50

Leptin receptor unresponsive to STAT signaling decreases

Question 51

Results of decreased STAT signaling

Answer 51

Increased appetite Decreased energy expenditure Increased obesity and diabetes risk

Question 52

Repeated activation of _______ leads to leptin resistance

Answer 52

SOCS3

Question 53

Foxo1 is a product of

Answer 53

AKT - from insulin pathway

Question 54

How to leptin and insulin pathways interact in T2DM?

Answer 54

Stat5 and STAT3 normally phosphrylate Foxo1 in the nucleus which leads to B cell health...if STAT3 and STAT5 are diminished, then less FOXO1 and worse B cell health