Medicines Design - Lloyd Flashcards
What is a glycation reaction?
A non enzymatic reaction between sugars (glucose) and nucleophillic groups
Glycation of haemoglobin often used as a measure of blood glucose
How can monosaccharides be classified?
And name 3 examples of them
By the number of carbon atoms that they have
Glucose (hexose)
Ribose and Deoxyribose (pentoses)
What configuration are most hexose monosaccharides have?
And so how many isomers are there?
D configuration
8 possible isomers
What is an anomer?
When either a newly formed isomer can either be in an (a) or (B) form
Eg, the ring closure of glucose (the far right alcohol)
What are the main points about reducing sugars?
Glycation can only occur with them (those with a free aldehyde/ketone)
They reduce Cu2+/Ag+ ions in basic solution, oxidising themselves
What is the most common residue to be glycated?
Lysine
What are the main consequences of glycation?
Glycated proteins are difficult to degrade, so there is a build up of damaged cells in the cell –> This causes auto-antibodies to be created….causing inflammation
Damage causes ROS –> creating an oxidising environment
What are the 4 main ways of measuring glycation?
Ion-exchange chromatography
Affinity chromotography/Gel electrophesis
Isoelectric focussing –> changes in the isoelectric point
Immunoassays such as ELISA –> detect certain antigens
What are the different types of GLUT transporters?
GLUT1 and 3 –> Km = 1mM
Found in all cell types, and always present
GLUT2 –> Km = 15-20mM
Only avaliable after a carbohydrate rich meal
GLUT4 –> Km = 5mM
Found in adipose/muscle tissue, and is the intermediate transporter
GLUT5 –> Transports dietary fructose from the small intestine (to convert it to glucose)
GLUT7 –> Transports dietary fructose and glucose from the small interstine and colon
What is the primary control enzyme of glycolysis?
PFK-1 –> which creates Frutose-6-phosphate
Has a higher activity at low levels of ATP
Activated by AMP
Substrates = ATP…..which is also an allosteric effector
