metabolisme kolesterol, lipoprotein dan apolipoprotein
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METABOLISME KOLESTEROL,LIPOPROTEIN DAN
APOLIPOPROTEIN
Meizly Andina
DEPARTEMEN BIOKIMIAFAKULTAS KEDOKTERAN
UNIVERSITAS MUHAMMADIYAH SUMATERAUTARA
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U
Cholesterol is present in tissues and inplasma either as: Free cholesterol or
as a storage form, combined with a long-chainfatty acid as cholesteryl ester.
In plasma, both forms are transported inlipoproteins
Cholesterol is an amphipathic lipid and assuch is an essential structural componentof membranes and of the outer layer ofplasma lipoproteins.
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Cholesterol is obtained from the diet
or synthesized by a pathway that occursin most cells of the body,
but to a greater extent in cells of theliver and intestine.
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The precursor for cholesterolsynthesis is acetyl CoA, which
can be produced
from
glucose fatty acids,amino acids.
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Me!a"#li$%e
&'#le$!e(#l
Fungsi cholesterol:Membentuk garam empedu Integritas membranMembentuk hormon steroidMembentuk Vitamin !
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A"$#()$i dan !(an$)#(!a$i
li)id Free Fatty acids, free cholesterol dan
"- monoacylglycerol .
#esintesa $% dan Cholesteryl esterdidalam sel-sel mucosa usus &n'im Fatty acyl Co( synthetase
)$hiokinase* mengaktifkan F( F( rantai sedang dan pendek
langsung ke sirkulasi porta danditransport oleh (lbumin.
+ipid lainnya ditransport olehCh lomicron didalam embuluh
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T(an$)#(!a$i
li)id$% dari Chylomicron dihydrolisa oleh
en'im +ipoprotein lipase
Chylomicron remnant.epar mensynthese $%, ditransport oleh
V++ihydrolisa oleh +ipoprotein lipase I+ ++)"" nm, memp. /00 molekul
ester Cholesterol dng +inolat* ++ diselubungi oleh : - 1hospholipid
- Cholesterol non
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T(an$)#(!a$i
li)id Fungsi ++: - transport cholesterolke
3aringan peripher
- kontrol synthese de no4o
cholesterol di 3aringan
+: transport cholesterol dari3aringanrusak5mati kesirkulasi. 6leh(cyltransferase cholest. ini
diesteri7kasidan oleh protein transfer
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Lipoprotein generalstructure
+ipoproteins are characteri'ed according to theirdensities.
$he lipoprotein densities 4ary depending on theirlipid composition.
$he free hydro8yl group of cholesterol is e8posed
on the surface of the lipoprotein to interact withwater. $hese proteins are referred to asa)#)(#!ein$*
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APOLIPOPROTEINS
(polipoproteins are the proteincomponents of the lipoproteins. $hey
are important in :. Maintaining the structural integrity
of the lipoproteins". #egulaton certain en'ymes which
act on lipoproteins!. #eceptor recognition
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P(#)e(!ie$ #+ S#%e H%anA)#li)#)(#!ein$
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STRU-TURE OFLIPOPROTEIN
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-#%)#$i!i#n #+ !'e Li)#)(#!ein$in Pla$%a #+ H%an$
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Lipoprotein Composition
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LIPOPROTEINFUN-TIONS
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F#( &la$$e$ #+ li)#)(#!ein$, .i$alized in !'e ele&!(#n %i&(#$)ea+!e( ne/a!i.e $!ainin/*-'yl#%i&(#n$, 0 !# 200 n% in dia%e!e(1 VLDL, 2 !# 30 n%1 HDL, !# n%1and LDL, 20 !# 2 n%*
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M#le&la( $!(&!(e #+ a &'yl#%i&(#n
$he surface is a layer of phospholipids,with head groups facing the a9ueousphase. $riacylglycerols se9uestered in theinterior )yellow* make up more than 0; ofthe mass.
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LIPOPROTEINMETABOLISM
$he two key en'yme systems arein4ol4ed in lipoprotein metabolism,
e8ample :
. +ipoprotein lipase releases freefatty acids and glycerol fromchylomicrons and V++ into thetissues
". +echitin cholesterol acyl transferase
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Me!a"#li& +a!e #+ &'yl#%i&(#n$*4A, a)#li)#)(#!ein A1 B56, a)#li)#)(#!ein B561 ,a)#li)#)(#!ein -1 E, a)#li)#)(#!ein E1 HDL, 'i/'5den$i!y li)#)(#!ein1 T7, !(ia&yl/ly&e(#l1 -,
&'#le$!e(#l and &'#le$!e(yl e$!e(1 P, )'#$)'#li)id1 HL, 'e)a!i& li)a$e1 LRP, LDL (e&e)!#(5(ela!ed )(#!ein*8 Only !'e )(ed#%inan! li)id$ a(e $'#9n*
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VERY LO: DENSITYLIPOPROTEIN 4VLDL8
Very low density lipoprotein )V++* isformed in the li4er from triacylglycerol and
cholesterol pro4ided by the tissue andwith the assistance of apoprotein 2-00.
It is mostly made in the body )>0;* with a
small portion )0;* deri4ed from the diet.
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$he V++ is e8ported and picks up apoprotein CIIand & in the blood. ?ote that since ++ is deri4edfrom V++, the V++ molecule contains the
apoproteins needed for both V++ and ++functions.
$he role of V++ is to transport and deli4er fattyacids to peripheral tissues. $riacylglycerolscontained in V++, as in chylomicrons, aresubstrates for lipoprotein lipase in capillaries.
LIPID
MOBILI;ATION
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$he mature V++ reaches the peripheral tissues)adipose tissue and skeletal and cardiac muscles* whereit is acted upon by the en'yme plasma lipoprotein lipase)+1+* which needs apoCII for its acti4ation.
$he action of this en'yme results in hydrolysis oftriglycerides into glycerol and free fatty acids.
$he fatty acids are taken up by the cells in these tissues
and are either used in the production of energy )skeletaland cardiac muscles* or used in the synthesis of tissueor milk fat )adipose tissues and lactating mammaryglands.
LIPID
MOBILI;ATION
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(fter losing the main bulk of itstriglycerides, the V++ returns the
apoC back to the + and becomeV++ remnants )I+*.
$hen V++ remnants gi4e their apo&back to the + and become ++.
LIPID
MOBILI;ATION
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LIPID
MOBILI;ATION
-'a(a&!e(i$!i&$ #+ -#%%#n
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-'a(a&!e(i$!i&$ #+ -#%%#nHy)e(li)ide%ia
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-lini&al Mani+e$!a!i#n$ #+Hy)e(li)ide%ia
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Li)#)(#!ein Me!a"#li$% andA!'e(#$&le(#$i$
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A!'e(#%a in A(!e(y
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L#/5linea( (ela!i#n$'i) "e!9een LDL5- le.el$ and(ela!i.e (i$> +#( -HD
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Se>ian ?