Obesity

Question 1

What can decrease fat absorption?

Answer 1

Inhibition of lipase.

Question 2

How are fatty acids absorbed?

Answer 2

Fatty acids are emusified by bile salts.
Emulsion digested by lipase to form micells.
Fatty acidss and mono-glyceride leave micells and enter cells.
Fatty globules combine with protein forming chylomicons.
Chylomicrons removed from cell.
Enter lacteal.

Question 3

MOA of lipase.

Answer 3

Enzyme contains an active site serine residue.
Serine activated by deprotonation by neighbouring resiude. Attacks the glyceride and cleaves the ester bond.
Covalent acel enzyme intermediate is formed which is then hydrolysed by water to release fatty acid.

Question 4

MOA of Lipstatin?

Answer 4

Contains strained 4 membered ring ester that is prone to nucleophilic attack.
Ester is attacked by serine residue in panreatic lipase.
Natural tricylglyceride substrate, acylserine intermediate undergo hydrolysis to release the free fatty acid.
Irreveresible inhibitor.

Question 5

Why is lipstatin not used over orlistat?

Answer 5

Bc alkene in lipstatin make the molecule prone to oxidation upon storage and in vivo metabolism.

Question 6

What are the side effects of orlistat?

Answer 6

GI effects, steatorrhea, wind , faecal incontinence.