cholesterol Flashcards
(32 cards)
what does high plasma LDL levels mean?
high risk of CHD
Why do humans need cholesterol?
synthesis of: cell membranes/ steroid hormones/bile acids
what are the two major sources of cholesterol?
Exogenous–dietarysupply,e.g.eggs,shellfish
Endogenous–denovo synthesis in organs&tissues e.g.liver,intestines,ovaries,adrenals
is cholesterol water soluble?
no, it is water insoluble
what is cholesterol transported as?
water-soluble cholesterol lipoproteins
what makes up the inner fatty hydrophobic core?
cholesterol / cholesterol esters
triglycerides/free fatty acids(FFAs)
what makes up the outer hydropillic coat?
apolipoproteins
phospholipid
cholesterol
what are the key functions of Apolipoproteins?
Lipoprotein assembly & transport
Maintenance of structural integrity of lipoproteins Enzyme activation & inhibition
Cellular receptor binding
what are the 5 classes of lipoproteins?
VLDL/IDL/HDL/LDL/ CHYLOMICRONS
what are all the types of Apolipoproteins?
apoA, apoB-100, apoB-48, ApoA-1,apoA2, apoC
what are the 3 Pathways of Plasma Lipid Transport and Metabolism?
Exogenous (Intestinal) Pathway
Endogenous (Hepatic) Pathway
Reverse Cholesterol Transport
what are the pathways co-ordinated by?
the liver- to ensure balance
what happens in the exo-intestinal pathway?- in intestine walll
Lipid (cholesterol) synthesis in the intestinal wall
Dietary & biliary cholesterol -absorbed into enterocytes via the Niemann-Pick C1-Like 1 (NPC1L1) transporter
Esterified through acyl-coenzyme A:cholesterol acyltransferase (ACAT)
Packaged into apoB-48 containing & triglyceride-rich chylomicrons (CMs) by microsomal triglyceride transfer protein (MTP)
what happens in the exogenous pathway?- in blood
Lipid (cholesterol) transport in the blood
Triglyceride-rich CMs leave the intestine via lymphatic system & enter blood stream
Triglycerides in CM core are hydrolysed by endothelial lipoprotein lipase (LPL) to release free fatty acids (FFAs), as CMs pass through capillaries in muscle & adipose tissue
FFAs utilised for energy in muscle cells, or stored as fat in adipose tissue
Resulting chylomicron remnant particles are removed from plasma by the liver, viaapo
Ebinding to the remnant receptor (LRP) or LDL receptor (LDLR), for further metabolism
what happens in the Endogenous (Hepatic) Pathway?
Once inside hepatocytes, CM remnants are packaged with more cholesterol, cholesteryl esters & ApoB100 to form triglyceride-rich
VLDLVLDL particles are released into circulation & triglycerides in the core are hydrolysed by LPL to release FFAs, to be utilised for energy in muscle cells, or stored as fat in adipose tissue
The resulting IDL is either taken up directly by the liver or converted to LDL-C by hepatic lipase (HL)LDL-C is then taken up by peripheral tissues via the LDLR to meet local cholesterol needs
Any left-over LDL-C particles are finally removed by the liver via the LDLR
what happens in the reverse transport?
Return of excess LDL-C from peripheral cells to the liver by HDL
Nascent or pre-HDL (rich in apoA-I) particles, secreted directly from the gut and liver or generated from LPL-mediated lipolysis of triglyceride-rich CM & VLDL, enters the circulation
Remove free cholesterol from deposits in peripheral tissues via the ATP-binding cassette A1 (ABCA1)
Plasma lecithin-cholesterol acyltransferase (LCAT) converts free cholesterol in pre-HDL to cholesteryl ester (CE), resulting in mature a-HDL
a-HDL cholesterol is transported to the liver by a director indirect pathway
what happens in the direct pathway?
hepatocytes selectively take up cholesteryl ester from a-HDL via the scavenger receptor, class B, type 1 (SR-B1)
what happens in the indirect pathway?
a-HDL cholesteryl ester is exchanged for triglycerides in apoB-rich VLDL & LDL via the cholesteryl-ester-transfer protein (CETP)
what are the first generating agents?
Bile acid sequestrants
Fibric acid derivatives
Nicotinic acid group
what do bile acid seq do?
Bind bile acids & prevent enterohepatic cycling
dec Hepatic cholesterol levels
inc LDL-R expression- inc hepatic cholesterol uptake
what are the adverse effects of bile acid seq?
GIT interactions
pharmacokinetics
what do fibric acid derivatives do?
Effects mediated viaPPAR-receptoractivation
inc Uptake & b-oxidation of FFAin liver & muscle cells
inc Lipoprotein lipase activity incTG hydrolysis in VLDL & CM incelimination of TG-rich particles
what do nicotinic acids do?
decrease FFA mobilisation from peripheral tissues
dec TG synthesis &VLDL secretion
dec plasma LDL
dec apoA-I uptake by liver inc HDL & reverse cholesterol transport
what are the second gen agents?
statins
Selective cholesterol absorption inhibitors
