seminar week 1 - SS Flashcards
What are lipoproteins and the funciton
- Spherical macromolecular complexes.
- help transport pf lipids through blood stream betweem tissues- TAG, Cholestrol ester, cholestrol, fat-soluble vitamons)
general structure of lipoproteins
- non polar core: mostly TAG and cholestrol ester
- single surface layer amphipathic lipids: phospho and cholestrol
- protein moiety of lipoprotein=apolipoprotein or apoprotein
classification of LPP according to
a) denisty
b) electrophoretic mobilities
LOW TO HIGH
a: chylomikrony, VLDL, IDL, LDL, HDL
b: chylomricon, LDL, VLDL, HDL
Class of LPP according to
a. triacylglycerol
b. choelstrol
c.phospholipid
d. proteins
LOW TO HIGH
a. HDL-LDL-VLDL-CHOLYMIKRON
b. CHOLY-VLDL-HDL-LDL
c. CHYLO-VLDL-LDL-HDL
d. CHYLO-VLDL-LDL-HDL
what are the functions of apoproteins
- form part of structure of lipoprotein(apoB, struc comp of VLDL and chylo)
- enzyme cofactors(apoC-11 doe LPP lipase, apoA-1 doe lecithin: cholestrol acyl transferase (LCAT), enzyme inhibitors like apo a-2 and apo c3 for lipase)
- act as ligands for interaction with lipoprotein receptors in tissues(apoB-100 and apoE for LDL receptor, apo-1 for HDL receptor)
Function of Chylomicrons and its assembly
function: transport of all dieatry lipids into circulation
assembly:
- intestinal mucosal cells
- carry dietayr(Exogenous ) TAG, chole, fat soluble vit and esters–>peripheral tissues
- apoliprotein synthesis:
- apo B-48 in RER
- long chain esterified–>yield TAG in mucosal cells and with other dietary thing–>incorportaed into LP in SER - assembly of apolipoproteins and lipids–>chylo: need microsomal TAG trasnfer protein
- secretory vesicles–>exocytosis - lymphatic sys –>syst circulation
what is nascent CM modification
- incomplete
- receive apoE and apoC-II from HDL
- Apoc-11–>act LPL
degradation of TAG by LPL
LPL: extracellular enzume, anchored by heparan sulfate. Hydrolyzes TAG in CM –>FFA +glycerol.
- FFA stored
-glycerol used by liver
what happens with the CM remnants: formation and digestion
- apoC-11 –>HDL
- remnant remove dby liver
- CM remnants bind to receptors–>apo e–>hepatocytes by endocytosis. –>lysosome, apoproteins and cholestryl esters and other components are hydrolytically degraded–>AA, chol, FFA
- Free CH -de novo CH stnthesis in liver(allosterid inhibition of HMG-coa red and lowwe the enzyme cell content)
VLDL function and release
function: carry lipids from liver to peripheral tissus
release:
-apoB-100 in RER
- secreted–>blood bt liver as nascent VLDL. contain: TAG, choelstrol, cholestrol estera and phospholipid apob-100 , apoA-1
Modification of circulating VLDL
- apoC-2+apoE + VLDL form HDL
- TAG degreaded by LPL–>VLDL smaller
- apoC-2 and E–>HDL
- some TAG from VLDL–>HDL, same time as cholesttryl ester from HDL–>VLDL by CEPT
LDL production from VLDL in plasma
- Formation of VLDL remnants or intermediate-density lipoprotein(IDL)
- IDL: liver via LDL(apoB-100, E) receptor, or converted to LDL
LDL function and formation
function: transport choelstrol to the peripheral tissues(or return it to the liver)
formation
- from VLDL via IDL in plasma, contain apoB-100
- high con of choelstrol and esters, less TAG
- bind to LDL receptors(apoB-100(apo E receptors
- LDL
LDL : receptor mediated endocytosis
- LDL receptors: neg charhed glycoproteins clustered on membranes
- intracellular side: protein clathrin-stabilizises
- binding–>endocytosis–>endosomes
ph falls–>sep of LDL from receptor - receptors recycled
lipoprotein remnants –>lysosome–Zlysosomal enzymes–>chol, aa, FA and phos - reutilized
effect of endocytosed choelstrol on cell cholestrol content
nhibition of HMG-CoA reductase (cholesterol derived from CM, HDL, LDL)
* ECH formation – ACAT ( acyl-CoA cholesterol acyltransferase)
* low of LDL receptor synthesis
what participate in formation of atherosclerotic plaque
In addition to the highly specific and regulated LDL-mediated pathway,
scavenger receptor class A (SR-A) of macrophages, can bind oxidized LDL.
* Cholesterol esters accumulate in macrophages and cause their transformation
into “foam” cells, which participate in the formation of atherosclerotic plaque.
HDL function and formation
function: reverse cholestrol transport-from peripheral tissues to liver
- acr as repository for apoC-2 and apoE required in metabolism of CM and VLDL
fromation
- syntehsized and secreted from liver and intestine
- apoC-2 and apoE: in liver: form liver HDL–>interstinal HDL when in plasma
- nascent HDL: discoid phospholipid bilayer with apo A and free chol
HDL uptake of free CH
- Reverse cholestrol trabsport: atp-bidning casette transportter A1(ABCA1)
- hydrolysis of ATP to binding of substrae: cant cross membrane.
- it transfer chol from cell–>poorly lipiated particles like pre-HDL or apo A-1–>HDL3
Esterification of free CH
- cholestrol taken up by HDL–>esterified by LCAT
- LCAT and apo A-1 bidn to discoidal particles=> phos + free chol–>cholestryl esters+lysolechitim
- ninpolar choelstryl ester–>int bilareye
- lysolecthin–>plasma albumin
- nacent HDL–>poor HDL3 then HDL2 which carry esters to liver
- SR-B1 mediate uptake, it binds to HDL
Referance values of
- TCH
- HDL
-LDL
-TAG
TCH (total cholesterol) 5,17 mmol/l
HDL >1,03-2,00 mmol/l men
>1,20-2,20 mmol/l women
LDL < 3,4 mmol/l = TCH – (TAG/2.2 + HDL)
if TAG < 4.6 mmol/l
TAG 0,4-1,7 mmol/l
TCH = LDL + VLDL + HDL + C
Index parameters
TCH/HDL < 5.2
LDL/HDL < 3.5
DiSsorder of plasma LP metabolism-Dyslipoproteinemias
what types do we have
Primary: independant, geneteically
secondary: consequence
most common primary HLP
Familiar hypercholestrolemia (FH)
- Mutation in the LDLR gene(chr 19)
-increase of plasma CH depends on the type of mutation, and hetero or homozygosity(gene dosage effect)
- conseqeunces: skin xantomas and tendon xantelasma, arcus cornea, premature atherosclerosis
secondary DLP
- by other primary disease
- cardiovascular system is same
- treatment: primary disease and hypolipidemic drugs
- responds to dietary intervention
