Obesity

Question 1

How are fatty acids absorbed

Answer 1

Large fats are emulsified by bile salts
Emulsion digested by lipase to form micelles
Fatty acids and mono-glycerides leave micelles and enter cell
Fatty globules combine with protein forming chylomicrons
Chylomicrons removed from cell (extruded)
They enter lacteal (lymph capillary)

Question 2

What is a triglyceride broken down into

Answer 2

Ester of glycerol and 3 fatty acids

Question 3

what is the lipase mechanism of action

Answer 3

Serine activated by deprotonation from other residues
Attacks glyceride and cleaves ester bond
Covalent acyl enzyme intermediate is hydrolysed to release fatty acid

Question 4

What is Lipstatin an inhibitor of

Answer 4

Lipase

Question 5

What are features of lipstatin that give it a mechanism of action?

Answer 5

Contains 4 membered ring ester - prone to nucleophilic attack
Acyl serine intermediate is stable- essentially an irreversible inhibitor

Question 6

Why do we use tetrahydrolipstatin and not lipstatin

Answer 6

Alkenes in lipstatin make molecule oxidise in storage
Therefore we use a hydrogenated form (ORLISTAT)

Question 7

What is a disadvantage of orlistat?

Answer 7

Poor bioavailability (however this reduces systemic side effects)