Chemical Pathology 2 - Lipoprotein metabolism, CVD and obesity Flashcards
What is the role of HDL?
Picks up excess cholesterol from the periphery and transports it to liver
What is the role of the enzyme CETP in cholesterol metabolism?
HDL to VLDL conversion
What is the key enzyme involved in cholesterol synthesis?
HMG CoA reductase
Which enzyme converts cholesterol to cholesteryl ester?
ACAT
What is VLDL constituted of?
ApoB, cholesteryl ester and triglyceride
What is the function of 7-alpha hydroxase in cholesterol metabolism?
Converts cholesterol to bile acids
What is the main component of mixed micelles?
Bile acids
Where are bile acids resorbed?
Terminal ileum
What controls the amount of cholesterol resorbed into the intestine?
Balance of 2 enzymes: NPC1L1 and ABC G5/G8
What is the inheritance pattern of familial hypercholesterolaemia type II?
Autosomal dominant
AD: LDLR, apoB, PCSK9 - main one
AR: LDLRAP1
What name is given to an inherited predeliction to high HDL, and what mutation causes this?
Familial hyper alpha lipoproteinaemia
= CETP deficiency
What condition is caused by ABC G5/G8 mutation?
Phytosterolaemia
What is phytosterolaemia?
Inherited condition that allows plant sterols to enter the plasma freely, which are more athrogenic than cholesterol itself
Recall 3 clinical signs of hypercholesterolaemia
Xanthalasma
Arcus
Tendon xanthoma
How can you examine for tendon xanthoma?
Feel back of ACL
What are the different types of primary hypertriglyceridaemia?
Familial Type I: Lipoprotein lipase or apoCII def
Familial Type IV: increased synthesis of tglycerides
Familial Type V: apoAV deficiency
What is A-beta-lipoproteinaemia?
MTP, apoB48, apoB100 deficiency causing hypolipidaemia (low chylomicrons, VLDL, LDL)
Results in deficiencies in fat-soluble vitamins A,D,E,K and its associated complications
Recall 3 inherited conditions that can cause hypolipidaemia
A-beta-lipoproteinaemia (MTP deficiency, apoB48, apoB100 deficiencies)-very low VLDL, LDL (auto recessive) Hypo-beta-lipoproteinaemia (truncated apoB protein)-low LDL Tangier disease (HDL deficiency caused by ABC1 mutation)
What is the effect of statins on cholesterol levels?
Very effective at reducing LDL, also reduce triglyceride and increase HDL slightly
What is the effect of fibrate drugs on cholesterol levels?
Very effective at reducing triglycerides, also increases HDL
What is the role of PCSK9?
Binds LDLR and promotes its degradation
Evolocumab is a PCSK9 inhibitor - new kind of drugs
What is the mechanism of action of statins?
HMG coA reductase inhibition
