LIPID TRANSPORT LIPID TRANSPORT & STORAGE& STORAGEAbdul Salam M. SofroAbdul Salam M. SofroFaculty of MedicineFaculty of Medicine

YARSI UniversityYARSI University

Learning objectivesLearning objectives

By the end of lectures, the students By the end of lectures, the students are expected to:are expected to: Understand lipid transport in the body Understand lipid transport in the body

(or the blood plasma)(or the blood plasma) Recognize various lipoprotein and the Recognize various lipoprotein and the

role of liver in lipid transport and role of liver in lipid transport and metabolismmetabolism

Understand lipid storage for energy Understand lipid storage for energy reservereserve

Lipid are insoluble in waterLipid are insoluble in water

How to transport in the blood How to transport in the blood plasma?plasma? Solved by associating non-polar Solved by associating non-polar

lipid (TAG & cholesteryl ester) lipid (TAG & cholesteryl ester) with amphipathic lipids with amphipathic lipids (phospholipids & cholesterol) and (phospholipids & cholesterol) and protein to make water-miscible protein to make water-miscible lipoproteinlipoprotein

Four major lipid classes are Four major lipid classes are present in lipoprotein present in lipoprotein

Triacylglycerol (TAG)Triacylglycerol (TAG) PhospholipidsPhospholipids CholesterolCholesterol Cholesteryl esterCholesteryl ester

Another plasma lipid: Free Fatty Acids (FFA) only 5% of the total FA present in the plasma and the most metabolically active plasma lipid

Sites of action of the phospholipases A1, A2, C and D.

Phospholipid StructuresPhospholipid Structures

Phosphatidylcholine (PC)

Phosphatidylethanolamine (PE)

Phosphatidylserine (PS)

Cont.Cont. Chylomicron – derived from intestinal Chylomicron – derived from intestinal

absorption of TAGabsorption of TAG Very Low Density Lipoproteins (VLDL of pre-Very Low Density Lipoproteins (VLDL of pre-

ββ-lipoproteins) – derived from the liver for -lipoproteins) – derived from the liver for export of TAGexport of TAG

Low Density Lipoproteins (LDL or Low Density Lipoproteins (LDL or ββ--lipoproteins) – representing the final stage in lipoproteins) – representing the final stage in the catabolism of VLDLthe catabolism of VLDL

High Density Lipoproteins (HDL) or High Density Lipoproteins (HDL) or αα--lipoproteins) – involved in VLDL & lipoproteins) – involved in VLDL & chylomicron metabolism and also in chylomicron metabolism and also in cholesterol transport cholesterol transport

Function of lipoproteinsFunction of lipoproteins ChylomicronsChylomicrons

Transport triacylglycerols from intestines Transport triacylglycerols from intestines to other tissue – except kidneysto other tissue – except kidneys

VLDLVLDL Bind triacylglycerols in liver and carry Bind triacylglycerols in liver and carry

them to fat tissuethem to fat tissue LDLLDL

Carry cholesterol to peripheral tissuesCarry cholesterol to peripheral tissues HDLHDL

Bound to plasma cholesterol. Transport Bound to plasma cholesterol. Transport cholesterol to livercholesterol to liver

Composition of lipoproteins in human Composition of lipoproteins in human plasmaplasma

FractionFraction SourceSource ProteinProtein(%)(%)

Total Total lipidlipid(%)(%)

TAGTAG(%)(%)

ChylomicroChylomicronsns

ChylomicroChylomicronn

remnantsremnantsVLDLVLDLIDLIDLLDLLDL

HDL1HDL1HDL2HDL2HDL3HDL3

Pre-Pre-ββ-HDL-HDL

IntestineIntestineChylomicronsChylomicrons

Liver Liver (intestine)(intestine)

VLDLVLDLVLDLVLDL

Liver & Liver & intestineintestineVLDL VLDL

ChylomicronsChylomicrons

1-21-26-86-8

7-107-1011112121

3232333357577070

98-9998-9992-9492-94

90-9390-9389897979

6868676743433030

88888080

565629291313

2216161313--

Albumin-Albumin-FFAFFA

Adipose tissueAdipose tissue 9999 11 00

Protein moiety of a lipoprotein Protein moiety of a lipoprotein is known as apolipoprotein or is known as apolipoprotein or

apoproteinapoprotein One or more apolipoproteins are One or more apolipoproteins are

present in each lipoprotein:present in each lipoprotein: Apo A is major apoprotein of HDLApo A is major apoprotein of HDL Apo B is major apoprotein of LDL (Apo B-Apo B is major apoprotein of LDL (Apo B-

100), but is found also in VLDL (Apo B-100), but is found also in VLDL (Apo B-100) & chylomicrons (Apo B-48)100) & chylomicrons (Apo B-48)

Apo C-I, C-II & C-III are smaller Apo C-I, C-II & C-III are smaller polypeptides freely transferable between polypeptides freely transferable between several different lipoproteinsseveral different lipoproteins

Apo E (arginine rich) are present in Apo E (arginine rich) are present in VLDL & HDLVLDL & HDL

Apolipoproteins of human plasma Apolipoproteins of human plasma lipoproteinslipoproteins

ApolipoproteinApolipoproteinss

LipoproteinsLipoproteins Molecular Molecular Mass (Da)Mass (Da)

Apo A-IApo A-I HDL, ChylomicronsHDL, Chylomicrons 28,00028,000Apo A-IIApo A-II HDL, ChylomicronsHDL, Chylomicrons 17,00017,000Apo A-IVApo A-IV Secreted with chyomicrons Secreted with chyomicrons

but but Transfer to HDLTransfer to HDL

46,00046,000

Apo B-100Apo B-100 LDL, VLDL, IDLLDL, VLDL, IDL 550,000550,000Apo B-48Apo B-48 Chyloicrons, chylomicron Chyloicrons, chylomicron

remnantsremnants260,000260,000

Apo C-IApo C-I VLDL, HDL, chylomicronsVLDL, HDL, chylomicrons 7,60007,6000Apo C-IIApo C-II VLDL, HDL, chylomicronsVLDL, HDL, chylomicrons 8,9168,916Apo C-IIIApo C-III VLDL, HDL, chylomicronsVLDL, HDL, chylomicrons 8,7508,750

Apo DApo D Subfraction of HDLSubfraction of HDL 19,30019,300Apo EApo E VLDL, IDL, HDL, VLDL, IDL, HDL,

Chylomicrons,Chylomicrons,Chylomicron remnantsChylomicron remnants

34,00034,000

Note:Note:

FFAs in the plasma arise from FFAs in the plasma arise from lipolysis of TAG in adipose tissue or lipolysis of TAG in adipose tissue or as a result of the action of as a result of the action of lipoprotein lipase during uptake of lipoprotein lipase during uptake of plasma TAG into tissues. They found plasma TAG into tissues. They found in combination with albumin, rapidly in combination with albumin, rapidly metabolized to form energy or metabolized to form energy or esterified, the level may arise in esterified, the level may arise in uncontrolled DMuncontrolled DM

TAG is transported from the TAG is transported from the intestinesintestines in in chylomicronschylomicrons and from the and from the liverliver in in VLDL.VLDL.

Chylomicrons are found in chyle formed Chylomicrons are found in chyle formed by the lymphatic system draining the by the lymphatic system draining the intestine and responsible for the intestine and responsible for the transport of all dietary lipids into the transport of all dietary lipids into the circulation.circulation.

Smaller & denser particles having the Smaller & denser particles having the physical characteristics of VLDL are also physical characteristics of VLDL are also to be found in chyle. Their formation to be found in chyle. Their formation occurs even in the fasting state, their occurs even in the fasting state, their lipids originating mainly from bile & lipids originating mainly from bile & intestinal secretionintestinal secretion

Chylomicrons & VLDL are rapidly Chylomicrons & VLDL are rapidly metabolized. Larger particles are metabolized. Larger particles are catabolized more quickly than smaller catabolized more quickly than smaller ones.ones.

Liver does not metabolize native Liver does not metabolize native chylomicrons or VLDL significantlychylomicrons or VLDL significantly

TAG of chylomicrons & VLDL are TAG of chylomicrons & VLDL are hydrolyzed by lipoprotein lipase hydrolyzed by lipoprotein lipase located on the walls of blood located on the walls of blood capillariescapillaries

The action of lipoprotein lipase The action of lipoprotein lipase (results in the loss of approx. 90% of (results in the loss of approx. 90% of TAG of chylomicron & the loss of Apo TAG of chylomicron & the loss of Apo C) forms remnant lipoproteins or C) forms remnant lipoproteins or chylomicron remnant.chylomicron remnant.

Liver is responsible for the uptake of Liver is responsible for the uptake of remnant lipoproteins, mediated by a remnant lipoproteins, mediated by a receptor specific for Apo E.receptor specific for Apo E.

LDL is metabolized via the LDL LDL is metabolized via the LDL receptorreceptor

HDL takes part in both lipoprotein HDL takes part in both lipoprotein TAG & cholesterol metabolismTAG & cholesterol metabolism

Liver plays a central role in lipid Liver plays a central role in lipid transport & metabolism:transport & metabolism: Facilitate digestion & absorption of Facilitate digestion & absorption of

lipids by the production of bilelipids by the production of bile It has active enzyme systems for It has active enzyme systems for

synthesizing & oxidizing FA aand synthesizing & oxidizing FA aand synthetizing TAGs & phospholipidssynthetizing TAGs & phospholipids

It converts FA to ketone bodies It converts FA to ketone bodies (ketogenesis)(ketogenesis)

It plays an integral part in the It plays an integral part in the synthesis & metabolism of plasma synthesis & metabolism of plasma lipoprotein.lipoprotein.

Clinical aspects & othersClinical aspects & others Imbalance in the rate of TAG formation Imbalance in the rate of TAG formation

& export causes fatty liver & export causes fatty liver when when accumulation of lipid in the liver accumulation of lipid in the liver becomes chronic, fibrotic changes occur becomes chronic, fibrotic changes occur in the cell that progress to cirrhosis & in the cell that progress to cirrhosis & impaired liver function.impaired liver function.

Ethanol also causes fatty liver.Ethanol also causes fatty liver. Adipose tissue is the main store of TAG Adipose tissue is the main store of TAG

in the body.in the body. Lipolysis is controlled by hormone-Lipolysis is controlled by hormone-

sensitive lipasesensitive lipase

Increased glucose metabolism reduces the Increased glucose metabolism reduces the output of FFAoutput of FFA

Insulin reduces the output of FFA Insulin reduces the output of FFA fall in fall in circulating plasma FFA.circulating plasma FFA.

Several hormones promote lipolysis:Several hormones promote lipolysis: GlucocorticoidsGlucocorticoids Thyroid hormonesThyroid hormones CatecholaminesCatecholamines

Brown adipose tissue promotes Brown adipose tissue promotes thermogenesis.thermogenesis.