Obesity Flashcards
How has obesity been targeted through medications?
Appetite suppression (CNS acting, simulation of satiety), decreased absorption, increased metabolism
How is fat broken down and distributed?
Large fat droplets are emulsified by bile salts. Pancreatic lipase breaks down TAGs into glycerol and fatty acid chains. Short and medium chain fatty acids and glycerol are directly absorbed into the capillaries in the gut epithelial tissue. Longer chain fatty acids and monoglycerides form triglycerides and combine with proteins to form chylomicrons in the Golgi Apparatus. These vesicles are then transported to the lymph vessels.
What is a triglyceride?
An ester of glycerol and 3 fatty acids.
What does Lipase do?
The enzyme contains an active site serine residue. The serine residue becomes activated by deprotonation by neighbouring residues. It then attacks the glyceride and cleaves the ester bond. A covalent acyl enzyme intermediate is formed which is then hydrolysed by water to release the fatty acid.
What does Lipstatin do?
Lipstatin contains a strained four membered ring ester that is prone to nucleophilic attack. The ester ring is then attacked by the active site serine in lipase. The acylserine intermediate is stable and hydrolysing it requires ~24 hours, meaning it is basically irreversible.
What issues were associated with Lipstatin?
The alkene groups are easily oxidised in vivo hence the drug cannot be used.
Why is Orlistat used over Lipstatin?
Because the molecule is hydrogenated which removes the problem associated with Lipstatin metabolism. Orlistat also has poor oral bioavailability but this is useful as it avoids systemic side effects.
What side effects are associated with Orlistat?
Steatorrhea (fat in the faeces), flatulence, faecal incontinence. These side effects are an example of aversion therapy, which forces patients to avoid eating fats.
What hormone causes the feeling of hunger?
Ghrelin
What hormone causes the feeling of satiety?
Leptin
