Lecture 14 Flashcards
What is plasma protien binding
The degree at whcih medications attach to protiens
What is the active form of a drug
The amount of free drug that there is, not the amount bound to the protien
What form of albumin binds calcium
The bovine cow form of albUMIN (BSA)
What is glycation
No enzymes do this, happens at free primary amines (n term and lysine)
If you have high levels of sugar in the blood your protiens get modified
This is because when in the linear form the sugar can attach to the protein and cause glycation
What protiens mostly get glycated
Hemoglobin and HSA
How can diabetes be diagnosed
They actually use antibodies against the glycated HSA and hemoglobin to find ratio of glycated to non glycated
Fasting glucose test (overnight): gives idea of glucose levels in one day
HbA1c test: gives an idea of the glucose concentration over three months
Glycated Albumin test: give idea of glucose concentration over 2-3 week (shorter time)
This diagnoses dibetes type 2
Is it just HSA and hemoglobin that can be glycated
No
Any protien can get glycated over time
What is the nomenclature of glycated hemoglobin
HbA1c
What are the drugs that treat diabetes
Why do we use these
Levemir
Victoza (liraglutide)
Recombinant HSA protiens (Albiglutide) : conjucgate HSA to whatever insulin drug
All so we can conjugate these drugs to HSA to increase its half life (since bound)
What is levemir
A myristoyl group added to insulin, lipidated
Lipidation Makes it bind to HSA to make HSA a carrier of the drug
Explain the glucose metabolism path way
There is starch from food that turns into glucose in the intestine
Most absorbed some unabsorbed (turns to poop)
If absorbed goes to blood where it’s taken into cells by insulin giving cells a signal to take up the sugar
In the cell is can be stored as glycogen in the liver or used as atp in the muscle
Explain what happens in the glucose pathway if insulin isn’t taken up by cells
In the blood it can be filtered to the kidney to be released as urine (this is how tested for diabetes)
During filtration there could be too much sugar in the blood so the pancreatic beta cells make more insulin so more sugar gets taken up by cells
What is GLP-1 and what does it do in the glucose metabolism pathway
If low amount of sugar in the blood , GLP-1 (glucose like peptide) is active and breaks down the stored glycogen
This indirectly increases insulin since now more glucose in blood
Good way to make insulin
What is victoza
A glucagon like peptide , glucagon is palmitolated on a glutamate that’s attached to a lysine
A agonist because it indirectly promotes insulin levels to go up
Binds to HSA because of plamitoyl group, promoted producting of insulin for anti diabetic
What are recombinant fusion protiens
Fuse hsa with the drug
examples 1:
Albuferon: fuse HSA with compound called interferon alpha
It is a cytokine that stimulates the immune system to make it more active
But less effective for cancer and more effective for viruses
Ex 2:
albiglutide: HSA couple to GLP-1
It’s GLP-1 receptor agonist (activates the receptor )
Bind to the receptor with is a gpcr to indirectly increase insulin levels
What is ozempic
What is wegovy
Victoza was liraglutide
Ozempic is semaglutide
Liraglutide was getting cleaved by a protease
Semaglutide has an unnatural amino acid that makes it protease resistant , this makes weight loss happen in addition to treating diabetes
Wegovy is actually purposely designed for weight loss
What length of fatty acid chain is in semaglutide (ozempic) and why
C18
The potentcy (how active the drug it) is lower but bind to HSA better, meaning you need fewer injections of it and gives a longer lasting result
So the length of the lipid is optimized to get maximal bing to HSA , low potency but higher binding to HSA less injections
Why does semaglutide make weight loss
It slows does the release of food from the stomach Making people feel full for longer
But there are a lot of side effects
What special about semaglutide now
Many diff versions are coming out
What parts of HSA are modified
The n term, the lysines, the cys 34
What type of protien is insulin
How else did they modify it
Preproprotien (modified twice)
Insulin degludec:
A lysine group of a diacid is attached to the proline in the insulin
Dcreases the number of injection of insulin needed
What else can be conjugated to HSA
Cisplatin
