Module 7: V7 - V11 Flashcards
What happens when blood glucose drops below 4.5 mM?
glucagon release is triggered by the pancreas which results in resting [glucose] in blood = 5.0 mM
What does glucagon release result in?
an increase in blood glucose levels
What does glucagon activate?
gluconeogenesis and glycogenolysis in the liver = increase glucose production
What does glucagon inhibit?
glycolysis and glycogenesis = decrease glucose storage / breakdown
What are priority tissues for glucose supply during fasting?
the brain and red blood cells
Why do red blood cells require glucose as a priority?
because they do not have mitochondria which is a cellular adaptation that prevents them from using up the oxygen they are transporting
What is glucagon?
a peptide hormone primary messenger which is synthesised in the ɑ cells of the pancreas
What is the glucagon receptor (and β-adrenergic receptor)?
a 7 transmembrane receptor since it contains 7 transmembrane ɑ-helices (GPCR)
What is cAMP?
secondary messenger which is made from ATP by the enzyme adenylate cyclase (AC)
What is the role of cAMP-dependent protein kinase or protein kinase A (PKA) in signalling?
cAMP activates PKA allosterically and when activated PKA phosphorylates several protein targets on Ser/Thr residues
Which enzymes is cAMP-dependent protein kinase able to target?
phosphorylase kinase which activates glycogen phosphorylase
l-pyruvate kinase, glycogen synthase, CREB protein which causes the transcription of PEPCK gene -> PEPCK
What happens when bifunctional PFK-2/FBPase-2 enzyme is phosphorylated by PKA?
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
What is the significance of bifunctional PFK-2/FBPase-2 enzyme?
able to determine whether gluconeogenesis or glycolysis is going to occur
What happens when l-pyruvate kinase is phosphorylated by PKA?
inhibiting PK activity shuts down the conversion of PEP to pyruvate slowing the feed into TCA cycle, tuse promoting gluconeogenesis
What happens when glycogen synthase is phosphorylated by PKA?
↓ 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
What happens when PKA phosphorylates the CREB protein?
results in expression of the PEPCK gene and ↑ production of PEPCK enzyme which converts oxaloacetate to PEP resulting in ↑ gluconeogenesis and glucose production
How is adrenaline synthesised? Where is it released?
from tyrosine in 4 steps via dopamine intermediate
from the adrenal gland
What is adrenaline involved in?
fright-flight-fight response largely targeting muscle, but also hits liver cells
How are β-adrenergic receptors activated?
adrenaline binding -> GDP is substituted for GTP -> adenylate cyclase is activated by G protein -> ↑ conversion of ATP to cAMP -> activation of PKA
How does adrenaline signalling affect the liver and muscle differently?
adrenaline switches on gluconeogenesis and glycogenolysis in the liver
in the muscle adrenaline switches on glycolysis and glycogenolysis
How are different effects achieved in the liver and the muscle in regards to bifunctional PFK-2/FBPase-2 enzyme?
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
How are different effects achieved in the liver and the muscle in regards to pyruvate kinase?
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
What happens when the brain tells muscles to get moving?
Ca2+ release stimulates both muscle contraction and glycogenolysis
What is the postprandial state?
the state after a meal
What is insulin?
peptide hormone which has two chains (A and B) linked by two -S-S- bonds
How is insulin synthesised?
synthesised as preproinsulin in the pancreas; pre-peptide and C-peptide is cleaved to yield active hormone
What is the mature form of insulin secreted by?
β-cells of the pancreas
Which pathways are activated by insulin (required to drop blood glucose)?
GLUT4 to membrane glycolysis amino acid uptake and protein synthesis fatty acid synthesis glycogen synthesis
Which pathways are inhibited by insulin (required to stop glycogen breakdown)?
TAG breakdown
gluconeogenesis
glycogen breakdown
How does insulin signalling affect glycogen synthase?
blocks inactivation of glycogen synthase (GS is more active)
How does insulin signalling affect GLUT4?
sends more GLUT4 to the membrane
What is beneficial about insulin inhibition of glycogen phosphorylase?
prevents breakdown of glycogen
Which molecule is central to metabolism?
acetyl-CoA
How can one protein be both a kinase and a phosphatase? What genetic mechanism(s) could have given rise to such a protein?
development of separate domains which have different enzymatic functions as a result of small changes to the genetic code over time
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?
this is because more glucose is required by the muscle to be broken down and converted into ATP
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?
carbohydrates can be converted into intermediates such as pyruvate and acetyl-CoA which can then be converted into fats
