LIPID TRANSPORT & STORAGE

Abdul Salam M. Sofro Faculty of Medicine YARSI University

Learning objectives

By the end of lectures, the students are expected to:

Understand lipid transport in the body (or the blood plasma) Recognize various lipoprotein and the role of liver in lipid transport and metabolism Understand lipid storage for energy reserve

Lipid are insoluble in water

How to transport in the blood plasma? Solved by associating non-polar lipid (TAG & cholesteryl ester) with amphipathic lipids (phospholipids & cholesterol) and protein to make water-miscible lipoprotein

Four major lipid classes are present in lipoprotein

Triacylglycerol (TAG) Phospholipids Cholesterol Cholesteryl 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 Structures
Phosphatidylcholine (PC)

Phosphatidylethanolamine (PE)

Phosphatidylserine (PS)

Cont.

Chylomicron derived from intestinal absorption of TAG Very Low Density Lipoproteins (VLDL of pre-lipoproteins) derived from the liver for export of TAG Low Density Lipoproteins (LDL or -lipoproteins) representing the final stage in the catabolism of VLDL High Density Lipoproteins (HDL) or -lipoproteins) involved in VLDL & chylomicron metabolism and also in cholesterol transport

Function of lipoproteins

Chylomicrons
Transport triacylglycerols from intestines to other tissue except kidneys

VLDL
Bind triacylglycerols in liver and carry them to fat tissue

LDL
Carry cholesterol to peripheral tissues

HDL
Bound to plasma cholesterol. Transport cholesterol to liver

Composition of lipoproteins in human plasma

Fraction
Chylomicrons Chylomicron remnants VLDL IDL LDL

Source
Intestine Chylomicrons Liver (intestine) VLDL VLDL

Protein (%)
1-2 6-8 7-10 11 21

Total lipid (%)

98-99 92-94 90-93 89 79

TAG (%)
88 80 56 29 13

HDL1 HDL2 HDL3 Pre--HDL

Albumin-FFA

Liver & intestine VLDL Chylomicrons

32 33 57 70
99

68 67 43 30
1

2 16 13 0

Adipose tissue

Protein moiety of a lipoprotein is known as apolipoprotein or apoprotein

One or more apolipoproteins are present in each lipoprotein:

Apo A is major apoprotein of HDL Apo B is major apoprotein of LDL (Apo B-100), but is found also in VLDL (Apo B-100) & chylomicrons (Apo B-48) Apo C-I, C-II & C-III are smaller polypeptides freely transferable between several different lipoproteins Apo E (arginine rich) are present in VLDL & HDL

Apolipoproteins of human plasma lipoproteins

Apolipoproteins Lipoproteins Molecular Mass (Da)

Apo A-I
Apo A-II Apo A-IV

HDL, Chylomicrons
HDL, Chylomicrons Secreted with chyomicrons but Transfer to HDL

28,000
17,000 46,000

Apo B-100
Apo B-48 Apo C-I Apo C-II Apo C-III Apo D Apo E

LDL, VLDL, IDL

Chyloicrons, chylomicron remnants VLDL, HDL, chylomicrons VLDL, HDL, chylomicrons VLDL, HDL, chylomicrons Subfraction of HDL VLDL, IDL, HDL, Chylomicrons, Chylomicron remnants

550,000
260,000 7,6000 8,916 8,750 19,300 34,000

Note:

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

TAG is transported from the intestines in chylomicrons and from the liver in VLDL. Chylomicrons are found in chyle formed by the lymphatic system draining the intestine and responsible for the transport of all dietary lipids into the circulation. Smaller & denser particles having the physical characteristics of VLDL are also to be found in chyle. Their formation occurs even in the fasting state, their lipids originating mainly from bile & intestinal secretion

Chylomicrons & VLDL are rapidly metabolized. Larger particles are catabolized more quickly than smaller ones. Liver does not metabolize native chylomicrons or VLDL significantly TAG of chylomicrons & VLDL are hydrolyzed by lipoprotein lipase located on the walls of blood capillaries

The action of lipoprotein lipase (results in the loss of approx. 90% of TAG of chylomicron & the loss of Apo C) forms remnant lipoproteins or chylomicron remnant. Liver is responsible for the uptake of remnant lipoproteins, mediated by a receptor specific for Apo E. LDL is metabolized via the LDL receptor HDL takes part in both lipoprotein TAG & cholesterol metabolism

Liver plays a central role in lipid transport & metabolism: Facilitate digestion & absorption of lipids by the production of bile It has active enzyme systems for synthesizing & oxidizing FA aand synthetizing TAGs & phospholipids It converts FA to ketone bodies (ketogenesis) It plays an integral part in the synthesis & metabolism of plasma lipoprotein.

Clinical aspects & others

Imbalance in the rate of TAG formation & export causes fatty liver when accumulation of lipid in the liver becomes chronic, fibrotic changes occur in the cell that progress to cirrhosis & impaired liver function. Ethanol also causes fatty liver. Adipose tissue is the main store of TAG in the body. Lipolysis is controlled by hormone-sensitive lipase

Increased glucose metabolism reduces the output of FFA Insulin reduces the output of FFA fall in circulating plasma FFA. Several hormones promote lipolysis:

Glucocorticoids Thyroid hormones Catecholamines

Brown adipose tissue promotes thermogenesis.