ChemPath - Lipoprotein metabolism Flashcards
What are the types of lipoprotein metabolism disorders
Primary hypercholesterolaemia
Primary hypertriglyceridaemia
Primary mixed hyperlipidaemia
Hypolipidaemia
What are the types of Primary Hypercholesteraemia and what is the associated pathology
Familial hypercholesteraemia:
- AD: LDLR, apoB, PCSK9
- AR: LDLRAP1
Polygenic hypercholesteraemia: several polymorphisms
Familial hyper(a)-lipoproteinaemia: CETP deficiency
Phytosterolaemia: ABC G5 & G8
What are the types of primary hypertriglyceridaemia and what are the associated pathologies
Familial type I: lipoprotein lipase of apoC II deficiency
Familial type V: apoA V deficiency
Familial type IV: increased synthesis of TG
What are the types of primary mixed hyperlipidaemia
Familial combined hyperlipidaemia
Familial dys(b)lipoproteinaemia
Familial hepatic lipase deficiency
What are the causes of hypolipidaemia and what are the associated pathologies
(A)(B)lipoproteinaemia: MTP deficiency
Hypo(B)lipoproteinaemia: truncated apoB protein
Tangier disease: HDL deficiency
Hypo(a)lipoproteinaemia: apoA-I mutations
What are the types of lipoprotein in order of density
Chylomicron (least)
Free fatty acid
very low density lipoprotein
Low density lipoprotein
Intermediate density lipoprotein
High density lipoprotein
What is the role of PCSK9 in lipoprotein metabolism
Binds LDLR and promotes its degradation
Loss of function mutation of PCSK9 → lower LDL levels
Novel form of LDL-lowering therapy is Anti-PCSK9 MAb
What is the management for hyperlipidaemia
First line: lifestyle (dietary modification and exercise)
Second line: Statin therapy
Third line: ezetimibe
What is the management for obesity
First line: conservative (Exercise and diet)
Second line: none for sustained weight loss
- Orlistat
Third line: bariatric surgery
What is the MOA for statins and what are the side effects
HMG-CoA reductase inhibitor
Reduces intrinsic synthesis of cholesterol in the liver
Side effects – myopathy/rhabdomyolysis, fatigue
What is the MOA of Orlistat and what are the side effects
Pancreatic lipase inhibitor
SE: profound flatus, diarrhoea
What is rimonabant
Cannabinoid antagonist
Discontinued due to high risk of suicide
