Hormonal Regulation

Question 1

Hypothalamus/pituitary gland function

Answer 1

Controls appetite and stress

Question 2

Adipocytes function

Answer 2

Secrete adipokines (appetite and metabolic activity)

Question 3

Adrenal glands function

Answer 3

Secrete catecholamines (epinephrine, norepinephrine)

Question 4

Pancreas function

Answer 4

Secretion of glucagon (catabolic) and insulin (anabolic)

Question 5

Glucagon is a [blank] homrone

Answer 5

catabolic

Question 6

Glucagon is secreted by [blank] and function is to

Answer 6

Secreted by pancreatic alpha cells and restores blood glucose levels (receptor expressed mainly in liver, kidney and adipose tissue)

Question 7

Hormonal signalling step 1 (catabolic = glucagon)

Answer 7

Hormone binds to a G-protein-coupled receptor
-G-proteins are guanine-nucleotide binding proteins
-Heterotrimeric complex (Gα, β and γ)
-Gα can bind GDP or GTP (active when bound to GTP)

Question 8

Hormonal signalling step 2 (catabolic = glucagon)

Answer 8

Binding of the hormone to its receptor leads to a change in conformation of the receptor that allows the recruitment of the G-proteins complex.

Question 9

Hormonal signalling step 3 (catabolic = glucagon)

Answer 9

This interaction allows the exchange of the GDP located on the Gα subunit for a new molecule of GTP.
The Gα -GTP complex detaches from the G-protein complex.

Question 10

Hormonal signalling step 4 (catabolic = glucagon)

Answer 10

Adenylyl cyclase (also called adenylate cyclase) is activated by binding of the active Ga (loaded with a GTP).
-The enzymatic activity of adenylyl cyclase take places in the cytoplasm.
-Adenylyl cyclase catalyzed the conversion of ATP into cyclic AMP (cAMP)

Question 11

Cyclic AMP (cAMP) function

Answer 11

is a second messenger important for many biological processes:
1) Regulation of glycogen, carbohydrates and lipids metabolism
2) cAMP is an activator of PKA (Protein kinase A)

Question 12

Hormonal signalling step 5 (catabolic = glucagon)

Answer 12

5. cAMP molecules bind to the regulatory subunits of PKA.
   -PKA is composed of two catalytic and two regulatory subunits.
   -In absence of cAMP, the regulatory units inhibit the activity of the catalytic subunits.
   -Binding of cAMP to the regulatory subunits of PKA causes a change in conformation in these subunits
   -The change in conformation release the catalytic subunits.

Question 13

Hormonal signalling step 6 (catabolic = glucagon)

Answer 13

The free catalytic subunits of PKA are now activated and can phosphorylated key regulating enzyme implicated in various metabolic pathway.

Question 14

How to restrict the effect of cAMP

Answer 14

To restrict the effect of cAMP, excess cAMP is converted to AMP by members of the phosphodiesterase (PDE) family.

Question 15

Homronal signalling pathway 9 steps summarized

Answer 15

1. Catabolic hormone receptors are coupled to G-proteins
2. Binding of the hormone leads to activation of the receptor
3. Receptor activation is mediated by the G-protein
4. Upon activation, the Gα monomer dissociates
5. Gα diffuses and activates adenylate cyclase (AC)
6. Adenylate cyclase converts ATP to cAMP
7. cAMP activates the cAMP-dependent protein kinase A (PKA)
8. PKA phosphorylates target regulatory enzymes
9. Phosphodiesterase (PDE) converts cAMP into AMP in order to attenuate the catabolic effect

Question 16

Key regulatory enzyme of glycogen synthesis

Answer 16

Glycogen synthase

Question 17

Key enzyme of glycogen breakdown

Answer 17

Glycogen phosphorylase

Question 18

Glucagons role in glycogenolysis

Answer 18

Question 19

Key regulatory enzyme of glycolysis

Answer 19

PFK and Pyruvate Kinase

Question 20

Key regulatory enzyme of gluconeogenesis

Answer 20

FBPase-1

Question 21

Role of F26BP in the liver and its impact on PFK-1 and FBPase-1 activity

Answer 21

Question 22

Glucagon role in gluconeogenesis

Answer 22

Question 23

Key regulatory enzyme of FAS

Answer 23

ACC (Acetyl-CoA carboxylase)

Question 24

Key regulator enzyme of cholesterol

Answer 24

HMG-CoA reductase

Question 25

Key regulatory enzyme of FA release from TAG

Answer 25

Perilipin and HSL

Question 26

Glucagon signalling on lipogenesis and ketogenesis

Answer 26

Question 27

Glucagon signalling on cholesterol biosynthesis

Answer 27

Question 28

Glucagon signalling on TAG homeostasis

Answer 28

Question 29

List of pathways glucagon regulates

Answer 29

Question 30

Insulin signalling (anabolic hormone) step 1

Answer 30

The binding of insulin to its receptor leads to a change in conformation resulting in the autophosphorylation of the receptor (tyrosine residues)

Question 31

Insulin signalling (anabolic hormone) step 2

Answer 31

Phosphorylated tyrosines are recognized by members of the Insulin Receptor Substrate family (mainly IRS1 and 2)

Question 32

Insulin signalling (anabolic hormone) step 3

Answer 32

This binding triggers the phosphorylation of tyrosine residues on IRS proteins

Question 33

Pip2 and Pip 3 are membrane lipids derived from

Answer 33

PI

Question 34

Insulin signalling (anabolic hormone) step 4

Answer 34

Phosphorylated IRS proteins are recognized by PI3-kinase (Phosphatidylinositol-4,5-bisphosphate 3-kinase)

Question 35

Insulin signalling (anabolic hormone) step 5

Answer 35

This binding leads to the activation of PI3K, which in turn phosphorylates PIP2 to make PIP3.

Question 36

Insulin signalling (anabolic hormone) step 6

Answer 36

Akt/PKB is recruited to the membrane by PIP3 where it will be phosphorylated by PDK1 (3-phosphoinositide-dependent protein kinase 1

Question 37

Phosphorylation of Akt/PKB by PDK1

Answer 37

Question 38

Insulin signalling (anabolic hormone) step 7

Answer 38

Once activated, Akt/PKB is released from the membrane. It will access the cytoplasm, where it will phosphorylate and inactivate GSK-3 (glycogen synthase kinase-3).

Question 39

Insulin signalling (anabolic hormone) step 8

Answer 39

Akt/PKB will also phosphorylate and activate PDE (phosphodiesterase), accelerating the conversion of cAMP into AMP.

Question 40

Insulin signallings effect on glycogen synthesis and break down

Answer 40

Question 41

Insulin signalling with glucose formation

Answer 41

**Note: Binding of insulin leads to the translocation of FLUT4 which occurs in the muscle

Question 42

Insulin signalling with glucose formation

Answer 42

**Note: Binding of insulin leads to the translocation of GLUT4 which occurs in the muscle

Question 43

Key regulatory enzyme for glucoose uptake

Answer 43

GLUT4

Question 44

Key enzyme for Fatty Acid storage

Answer 44

cAMP, LPL

Question 45

Insulin signalling in FA synthesis

Answer 45

Question 46

Insulin signalling in cholesterol synthesis

Answer 46

Question 47

Insulin signalling in TAG synthesis

Answer 47

Question 48

Summary of insulin and its metabolic effects

Answer 48

Question 49

Insulin pathway through all the systems we studied

Answer 49

Question 50

2 hormones that cause stress are

Answer 50

1) epinephrine 2) norepinephrine

Question 51

4 main effects of stress on metabolism and physiology

Answer 51