Module 7: V7 - V11

Question 1

What happens when blood glucose drops below 4.5 mM?

Answer 1

glucagon release is triggered by the pancreas which results in resting [glucose] in blood = 5.0 mM

Question 2

What does glucagon release result in?

Answer 2

an increase in blood glucose levels

Question 3

What does glucagon activate?

Answer 3

gluconeogenesis and glycogenolysis in the liver = increase glucose production

Question 4

What does glucagon inhibit?

Answer 4

glycolysis and glycogenesis = decrease glucose storage / breakdown

Question 5

What are priority tissues for glucose supply during fasting?

Answer 5

the brain and red blood cells

Question 6

Why do red blood cells require glucose as a priority?

Answer 6

because they do not have mitochondria which is a cellular adaptation that prevents them from using up the oxygen they are transporting

Question 7

What is glucagon?

Answer 7

a peptide hormone primary messenger which is synthesised in the ɑ cells of the pancreas

Question 8

What is the glucagon receptor (and β-adrenergic receptor)?

Answer 8

a 7 transmembrane receptor since it contains 7 transmembrane ɑ-helices (GPCR)

Question 9

What is cAMP?

Answer 9

secondary messenger which is made from ATP by the enzyme adenylate cyclase (AC)

Question 10

What is the role of cAMP-dependent protein kinase or protein kinase A (PKA) in signalling?

Answer 10

cAMP activates PKA allosterically and when activated PKA phosphorylates several protein targets on Ser/Thr residues

Question 11

Which enzymes is cAMP-dependent protein kinase able to target?

Answer 11

phosphorylase kinase which activates glycogen phosphorylase

l-pyruvate kinase, glycogen synthase, CREB protein which causes the transcription of PEPCK gene -> PEPCK

Question 12

What happens when bifunctional PFK-2/FBPase-2 enzyme is phosphorylated by PKA?

Answer 12

kinase domain becomes inactivated resulting in reduced production of F-2,6-bisP however the phosphatase domain will still be active allowing conversion of F-2,6-bisP to F-6-P

Question 13

What is the significance of bifunctional PFK-2/FBPase-2 enzyme?

Answer 13

able to determine whether gluconeogenesis or glycolysis is going to occur

Question 14

What happens when l-pyruvate kinase is phosphorylated by PKA?

Answer 14

inhibiting PK activity shuts down the conversion of PEP to pyruvate slowing the feed into TCA cycle, tuse promoting gluconeogenesis

Question 15

What happens when glycogen synthase is phosphorylated by PKA?

Answer 15

↓ activity resulting in ↓ movement of glucose into glycogen particles + PKA activates phosphorylase kinase which activates glycogen phosphorylase ↑ the breakdown of glycogen into glucose monophosphate which is converted into glucose

Question 16

What happens when PKA phosphorylates the CREB protein?

Answer 16

results in expression of the PEPCK gene and ↑ production of PEPCK enzyme which converts oxaloacetate to PEP resulting in ↑ gluconeogenesis and glucose production

Question 17

How is adrenaline synthesised? Where is it released?

Answer 17

from tyrosine in 4 steps via dopamine intermediate

from the adrenal gland

Question 18

What is adrenaline involved in?

Answer 18

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

Question 19

How are β-adrenergic receptors activated?

Answer 19

adrenaline binding -> GDP is substituted for GTP -> adenylate cyclase is activated by G protein -> ↑ conversion of ATP to cAMP -> activation of PKA

Question 20

How does adrenaline signalling affect the liver and muscle differently?

Answer 20

adrenaline switches on gluconeogenesis and glycogenolysis in the liver
in the muscle adrenaline switches on glycolysis and glycogenolysis

Question 21

How are different effects achieved in the liver and the muscle in regards to bifunctional PFK-2/FBPase-2 enzyme?

Answer 21

liver and muscle express different isoforms of the enzyme that controls F-2,6-bisP levels and PKA phosphorylation has opposite effect on these enzymes

Question 22

How are different effects achieved in the liver and the muscle in regards to pyruvate kinase?

Answer 22

muscle PK lacks the key serine residue that is phosphorylated by PKA in liver PK meaning muscle PK is not inhibited by adrenaline signaling
therefore glycolysis is suppressed in liver, but not in muscle

Question 23

What happens when the brain tells muscles to get moving?

Answer 23

Ca2+ release stimulates both muscle contraction and glycogenolysis

Question 24

What is the postprandial state?

Answer 24

the state after a meal

Question 25

What is insulin?

Answer 25

peptide hormone which has two chains (A and B) linked by two -S-S- bonds

Question 26

How is insulin synthesised?

Answer 26

synthesised as preproinsulin in the pancreas; pre-peptide and C-peptide is cleaved to yield active hormone

Question 27

What is the mature form of insulin secreted by?

Answer 27

β-cells of the pancreas

Question 28

Which pathways are activated by insulin (required to drop blood glucose)?

Answer 28

GLUT4 to membrane
glycolysis
amino acid uptake and protein synthesis
fatty acid synthesis
glycogen synthesis

Question 29

Which pathways are inhibited by insulin (required to stop glycogen breakdown)?

Answer 29

TAG breakdown
gluconeogenesis
glycogen breakdown

Question 30

How does insulin signalling affect glycogen synthase?

Answer 30

blocks inactivation of glycogen synthase (GS is more active)

Question 31

How does insulin signalling affect GLUT4?

Answer 31

sends more GLUT4 to the membrane

Question 32

What is beneficial about insulin inhibition of glycogen phosphorylase?

Answer 32

prevents breakdown of glycogen

Question 33

Which molecule is central to metabolism?

Answer 33

acetyl-CoA

Question 34

How can one protein be both a kinase and a phosphatase? What genetic mechanism(s) could have given rise to such a protein?

Answer 34

development of separate domains which have different enzymatic functions as a result of small changes to the genetic code over time

Question 35

If I am being chased by a tiger, why does adrenaline signalling need to decrease glycolysis in the liver, but increase glycolysis in the muscle?

Answer 35

this is because more glucose is required by the muscle to be broken down and converted into ATP

Question 36

In the 1980s people were worried about the health impacts of fatty foods. So, reduced fat processed foods were developed. They tasted terrible, and then sugar was added to make them more palatable. How is it that sugary foods can make you fat? Which key metabolic intermediate(s) might be involved in converting sugars to fats?

Answer 36

carbohydrates can be converted into intermediates such as pyruvate and acetyl-CoA which can then be converted into fats