Normal and deregulated metabolism Flashcards
Insulin promotes the intracellular uptake of which ion? [1]
K+
Which tissues use glucose as fuel?
Which organ is the exception and what does it use as a fuel source instead? [1]
Which tissues use glucose as fuel?
All tissues
Which organ is the exception and what does it use as a fuel source instead? [1]
Liver: fatty acid oxidation instead
How can triglycerides be used to produce ATP?
Triglycerides broken down by lipase in fatty acids and glycerol
Fatty acids can make acetyl coA via beta oxidation and therefore ATP
How much glucose does the brain cosume per day? [1]
Why is a steady glucose supply important for the brain? [1]
How much glucose does the brain cosume per day? [1]
120 g
Why is a steady glucose supply important for the brain? [1]
Brain has no store of glucose so must be supplied
How does body create fuel source at:
a) post absorb. state?
b) when glucose stores are used up?
c) continued fasting
d) further fasting
Post absorbative state:
- Muscle and adipose tissue reduce their glucose utilisation
If glucose stores are used up (24hr store) moves:
- triglyceride stores: fatty acids are used to make ATP via beta oxidation in cartinine shuffle.
- glucose made at the liver via gluconeogensis (using lactate, amino acids or glycerol) to continue a glucose supply
If continued fasting: ketogenesis occurs:
- Brain and RBC use glucose from hepatic and renal gluconeogenesis
- Other tissues use keto molecules as an additional fuel source
Prolonged fasting:
- Brain reduces glucose use; uses some ketone bodies (but glucose is still required)
- RBC use glucose from renal and hepatic GNG
How does body create fuel source at:
a) post absorb. state?
b) when glucose stores are used up?
c) continued fasting
d) further fasting
Post absorbative state:
- Muscle and adipose tissue reduce their glucose utilisation
If glucose stores are used up (24hr store) moves:
- triglyceride stores: fatty acids are used to make ATP via beta oxidation in cartinine shuffle.
- glucose made at the liver via gluconeogensis (using lactate, amino acids or glycerol) to continue a glucose supply
If continued fasting: ketogenesis occurs:
- Brain and RBC use glucose from hepatic and renal gluconeogenesis
- Other tissues use keto molecules as an additional fuel source
Prolonged fasting:
- Brain reduces glucose use; uses some ketone bodies (but glucose is still required)
- RBC use glucose from renal and hepatic GNG
What happens to electrolytes during starvation? [1]
Which electrolytes in particular? [2]
Loss of electrolytes: particularly phosphate and potassium
(insulin controls the uptake of K into the cell)
What is refeeding syndrome?
Which deficiences are like to get? [3]
What can it lead to? [2]
Upon refeeding, synthesis of glycogen, triglycerides, proteins
This requires intracellular ions, however these have been depleted throughout starvation. Get transport of ions (particularly K) intracellularly.
Causes a depletion of serum ion levels: can get Hypophosphataemia, hypokalamia, thiamine deficiencies
Leading to congestive heart failure and peripheral oedema
During the fasting state which processes are occurring in
a) muscle
b) liver
c) adipose
Muscle
* Glycogen is **broken down **(GLYCOGENOLYSIS) to provide ATP
Liver:
* GLYCOGENOLYSIS in liver releases glucose into bloodstream (reserve depleted in 24 h)
* GLYCOLYSIS is inhibited in the liver.
* Liver synthesises new glucose (GLUCONEOGENESIS) from amino acids, lactate, glycerol
Adipose tissue:
* Triglycerides are broken down in adipose tissues (LIPOLYSIS) – to provide glycerol (used in gluconeogenesis) and fatty acids
In post-absorb / fasting state which substance is used by the liver as a substrate for GNG? [1]
In post-absorb / fasting state which substance is converted to ketone bodies by the liver? [1]
Oxaloacetate is used by the liver as substrate for gluconeogenesis
Excess acetyl-CoA is converted into ketone bodies by the liver (KETOGENESIS), which then used to produce ATP
What type of receptor is insulin receptor? [1]
Tyrosine kinase receptor
Explain how insulin works to allow glucose into cell in healthy cells? [5]
- Insulin binds to insulin receptor
- Autophosphorylation of the receptor occurs
- IRS is phosphorylated by the receptor on Tyrosine residues
- Phosphorylated IRS can now bind to PI3K which moves from the cytoplasm
- Causes PIP2 to PIP3
- Causes activation of AKT pathwayand GLUT 4 to move to membrane
GLUT4 transporters are now inserted into the membrane
Glucose can cross the membrane & it can be stored
How can insulin resistance occur? [6]
Decrease in the number of insulin receptor
Decrease in the catalytic activity of the receptor
Increased activity of Tyrosine phosphatases
Decreased levels and function of GLUT4
Increased Ser/Thr phosphorylation of the receptor or of IRS
Decreased PI3K/Akt activity
Explain one mechanism of how obesity can cause deregulation in insulin resistance?
Pro-inflammatory cytokines, saturated FFAs, amino acids can activate Serine/Threonine kinases
Serine/Threonine kinases can phosphorylate IRS, reducing its Tyrosine phosphorylation and also increasing its degradation
Explain one mechanism of how obesity can cause deregulation in insulin resistance?
Pro-inflammatory cytokines, saturated FFAs, amino acids can activate Serine/Threonine kinases
Serine/Threonine kinases can phosphorylate IRS, reducing its Tyrosine phosphorylation and also increasing its degradation
When insulin binds, the cascade starts and IRS goes to the receptor but, because now IRS is phosphorylated on these amino acids, it cannot be phosphorylated by the receptor
The cascade stops so the message does not reach GLUT4 and the excess of glucose is not removed even if insulin is there
