Metabolisme lipoprotein(FILEminimizer)

7/25/2019 Metabolisme lipoprotein(FILEminimizer)

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Metabolism of Lipids andLipoproteins

Ajeng Diantini


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Lipids and Cardiovascular Disease

Evidence suggests :

there is positive correlation between the risk of developing

ischaemic heart disease and plasma LDL-cholesterol levels

and a negative one with those of HDL-cholesterol


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Atherogenesis

Lipid theory

esponse to !n"ury theory

#esenchymal theory

#utagenic theory


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Factors of Coronary HeartDiseases


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Cardiovascular Risk Factors


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Major Lipids of the Body $riglicerides %$riacylglycerols& : energy

reservoir'

(tructural components of membranes: )holesterol : precursor for steroid hormones

and bile acids *hospholipids: lipid comple+ consisting

phosphate and a nitrogenous base, lycolipids

!n blood stream' lipids are transported in theform of lipoproteins.


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.fter a fatty meal: the main of ingested $. in themucosal cells is absorbed into the lymph aschylomicrons which enter the blood mainlythrough the thoracic duct

.dipose tissue

Lipoprotein lipase %clearing factor lipase&

precursor of L*L is synthesi/ed in theadipocytes and transferred to an outer membrane

of the cells' where it is activated by heparin orrelated proteogycan' then transported to theendothelial cells of adipose tissue,

L*L controlled by insulin %promote activation&' and

adrenalin %inhibit activation&,


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.po )-!! is a cofactor for lipoprotein lipase' andthis apoprotein is transferred from HDL tochylomicrons or 0LDLs to activate the en/yme

when they reach endothelial cells,

.t the endothelial cells: hydrolysis of $. ofchylomicrons to monoglycerol 1 22.,

3 22. 1 monoacylglycerol from each $. cross thecell membrane, #ono. subse4uently hydrolysedto glycerol 1 22. %by mono. hydrolase&,

lycerol is released to circulation but the 2. areretained and synthesi/ed into $. in adiposetissue cells,


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Fase penetrasi sel dan intra luminal

asorpsi trigliserida


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Fase seluler asorpsi trigliserida


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R!L" !F #L$C!%" A&D '&%$L'&

.fter normal mi+ed meal'the plasmaglucose will rise and this cause the rise ofinsulin plasma, !nsulin enhances theactivation of L*L' so that circulating $.

are rapidly taken un into tissues, lucose also plays an important role in the

provision of glycerol-5-phosphate for thesynthesis of $. from 22. taken up fromthe chylomicrons,


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Cataolism of (riglyceride


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Lipid transport in the fasting state

)hylomicrons clearing : 67 hours' then theadipose tissue may begin to release its store of$. %by hs-Lipase&


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Li i l bl l


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Lipoprotein are water-soluble complexesof high molecular weight composed of

lipids (cholesterol, triglycerides,

phospholipids) and one or more specicproteins, called apolipoprotein.

Function of lipoproteins)Transport for water-insoluble lipids in theblood

%tructure )They form particles in which the hydrophilic moietiesof the phospholipids and apolipoproteins are arrangeat the surface and the hydrophobic triglycerides and

cholesteryl esters are oriented toward the interior to


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Classication$he lipoproteins are divided into various

categories according to density' asdetermined by ultracentrifugation

)hylomicrons:

D 8 7,9 g;ml 2ormed in the intestine' transport

e+ogenous triglycerides )omposed of 9< = 99, > lipid and 7, =

3 > protein 2loat to form a superficial layer on serum

allowed to stand overnight,


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Lipoptroteins


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LDL %Low-density Lipoproteins& d ? 6,769 = 6,7@5 g;ml transport cholesterol in the blood LDL arises as metabolic products of 0LDL )ontain appro+, A > lipid and 3 > protein

HDL %High Density Lipoproteins& d ? 6,7@5 = 6,36 g;ml contain appro+, 7 > lipid and 7 > protein are produced by the intestine and liver in precursor form'

then fully developed in plasma,

)apable of taking up cholesterol from cells andtransporting it back to the liver, HDL subfractions : HDL6 %6,7-6,7


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0LDL %0ery Low Density Lipioproteins&

d 8 6,77@ g;ml formed in the liver' transport endogenous

triglycerides

consist of lipid and 67-6 protein,

!DL %!ntermediate-density Lipoproteins&

d ? 6,77@ = 6,769 g;ml

found in the absence of metabolic diseases only

in very low concentration are thought to be metabolic products of 0LDL or

precursor particles of LDL


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Lipoproteins separated yelectrophoresis are classi*ed as) B-lipoproteins %LDL& pre B - lipoproteins %0LDL&

C-lipoproteins %HDL&

$he triglyceride-rich chylomicrons show almost no

migration at all and remain at the origin onsupporting media,

The -lipoproteins migrate with the -globulin.

pre - lipoproteins migrate with 2-globulins

-lipoproteins with 1-globulins


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!polipoprotein


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!polipoproteins


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Lipoproteins and apolipoproteins


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"sterication of Cholesterol


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#iosynthesis of $%L-Cholesterol


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&nternali'ation of L%L into the cell


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Metabolic pathways of lipid andlipoproteins

#a"or function of the plasma lipoprotein :

is transport of triglyceride from sites of synthesis inthe intestine or liver to sites of storage %adiposetissue&' energy use %muscles&' or metabolism %liver&,


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PROTECTIVE HDL

HDL is a Reverse Cholesterol

Transport.- HDL decreased LDL oxidation

(have an antioxidant function).- Paraoxonase (enzye present in HDL)

Prevents the accuulation of

Lipoperoxides in LDL.- HDL decreased expression of !C"#-$%

&C"#-$ and '-electin% induced

y T*+-.-


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+H! Classi*cation of hyperlipoproteinaemia


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Disorder of lipid metaolism

Hypertriglyceridemia :

- high level of chylomicron ' 0LDL or both, - turbid plasma

- associated with abdominal pain' pancreatitis' or symptomfree,

- reduce HDL' and;or increase LDL

Hypercholesterolemia:

- with little or no elevation of $' often is almost alwaysdue to raised LDL levels,

- #ain disorders that may produce a secondary increase

LDL and total chol: hypothyroidism' diabetes mellitus' nephrotic syndrome'

cholestasis Hyperchylomicronaemia:

- deficiency of L*L %lipoprotein lipase&


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Rare disorder of lipid metabolism

deficiencies of HDL ----premature )HD

- abnormal .po . result in e+cessive catabolism

of HDL

.po deficiency % abetalipoproteinemia' LDLdef& : impaired synthesis of chylomicron and0LDL,

------steatorrhea

Deficiency of L).$ ---accumulation of freechol-----premature atherosclerosis


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LIPIDS & LIPOPROTEINS

ANALYSIS.-

Cholesterol

Tri,lyceride

LDL-CholesterolHDL-Cholesterol

"po

Lp (a)

all-Dense LDL

x-LDL


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Parameter of Dislipidemia:

Ho, far and ,hy-

)hylomicron

$riglyceride

$otal cholesterol

)holesterol-LDL )holesterol-HDL

.po-.

.po-

atio .po .;.po

atio $otal )hol;HDL


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C

(trong pedictor of :6, #yocardial infarction

3, (troke

5, *eripheral vascular disease

, (udden cardiac death in individualswithout a history of heart disease


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ole of C inatherogenesis6, Local endothelial cell surface adhesion

molecule3, #onocyte chemoattractan protein-65, Endothelin-6

, Endothelial plasminogen activator inhibitor-6)* also:6, educes endothelial nitric o+ide bioactivity3, !ncreases the induction of tissue factor on

monocyte and LDL uptake og macrophage5, )o-locali/es with the complement #.)

%membrane attack comple+es& within arterylession


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$omocystein

!ncreased concentration of totalhomocystein %tHcy& correlate with )HD

(ulfur-containing amino acid with eachmolecule of Hcy containing one atom of

sulfur !t is formed during metabolism of

methionine and re4uires folic acid as co-

factor


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Metabolisme lipoprotein(FILEminimizer)

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