NUBIO Week 2: Concept 3 Lipids- Transport & Storage

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Lipoprotein Physiology: Overview (1/4) http://www.youtube.com/watch?v=4D6CqHpvVz8 Lipoprotein Physiology: Chylomicron (2/4) http://www.youtube.com/watch?v=xAqL9fLwnDs Lipoprotein Physiology: LDL (3/4) http://www.youtube.com/watch?v=4nXPQo4FdL8 Lipoprotein Physiology: HDL (4/4) http://www.youtube.com/watch?v=9u8YSD6StOg

Definitions • Apolipoprotein - a protein that binds to

lipids

• Cholesteryl ester - a compound of cholesterol and a fatty acid

• Triglyceride- a compound of glycerol and three fatty acids, an ordinary fat molecule

• Phospholipid- a compound of glycerol, two fatty acids, and an amino alcohol eg choline

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Lipid Transport & Storage • Chylomicrons

– Belong to a family of lipid-protein complexes lipoproteins

• Primary form of lipoprotein formed from exogenous dietary lipids

• Transport exogenous dietary lipids – Other lipoproteins (VLDL & LDL especially) transport

endogenous lipids from tissue to tissue to supply cellular needs.

• Lipoproteins differ according to ratio of lipid to

protein • This difference influences the density of the particle

e.g. LDL, HDL COPYRIGHT CENGAGE LEARNING

COPYRIGHT CENGAGE LEARNING Fig 5-14 pg 152

COPYRIGHT CENGAGE LEARNING Fig 5-15 pg 152

Lipid Transport & Storage • Apolipoproteins

– The protein component of the lipoproteins stablise the lipoproteins as they circulate in the blood

– Allows the lipoproteins to be recognised by specific cell receptors

– Stimulates certain enzymatic reactions – ApoB-48 is most important

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Lipid Distribution • Reformed lipid exits the enterocytes as chylomicrons, which then

undergo conversion to chylomicron remnants – The chylomicrons contain TAG, cholesteryl esters, phospholipids (PL), vitamins A

and E in the core, a monolayer of PL, free cholesterol, and apolipoprotein • Chylomicrons enter lymphatic vessels of the abdominal region first,

then into the blood – Continues up to 14 hours after consumption of a fatty meal – Peak blood plasma lipid levels occur usually 30 mins to 3 hours after

ingestion

• Deliver 80% dietary lipid to muscle and adipose and 20% delivered to liver as chylomicron remnants.

• Hydrolysis occurs at particular tissue sites for uptake, especially muscle and adipose tissue.

• Free fatty acids and diacylglcerol are released and absorbed

by the tissue cells.

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Triglyceride Storage • Lipoprotein lipase solubilises chylomicrons (lipolysis) resulting in a smaller

particle- the Chylomicron remnant. • Chylomicron remnants are relatively lower in TAG, but richer in cholesterol

& cholesterol esters.

• Chylomicron remnants are removed from the blood stream via hepatocyte endoctyotosis

• Nascent VLDL of liver origin also undergoes triacylglycerol stripping by

lipoprotein lipase resulting in the formation of a cholesterol rich LDL. • Within muscles cells, the free fatty acids are primarily used for energy • In adipose tissue the absorbed fatty acids are largely used for synthesis of

triacylglycerols

• Chylomicrons are cleared from the plasma in a matter of minutes and and VLDL in a matter of hours from the time they enter the bloodstream

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Role of the Liver in Lipid Metabolism

The liver plays an important role in the body’s use of lipids and lipoproteins

1. Synthesis of the bile salts 2. Synthesis of lipoproteins and thus transports fats 3. Synthesis of new lipids from non-lipid precursors e.g. glucose and amino

acids 4. Can take up and catabolise dietary lipids delivered to it. 5. The synthesis of fatty acids, monoaclyglycerols, diacylglycerols &

triacylglycerols, VLDL, HDL & LDL, glycerol, cholesterol. 6. Dietary MC free fatty acids may be used for energy, or to resynthesise

other lipids 7. Cholesterol and cholesteryl esters from chylomicron remnants may be:

a) Converted to bile salts and secreted in the bile b) Secreted into the bile as neutral sterol c) Incorporated into VLDL or HDL and released into plasma

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COPYRIGHT CENGAGE LEARNING Fig 5-16 pg 155

Role of Adipose Tissue in Lipid Metabolism

The adipose tissues shares with the liver an important role in the metabolism of lipids

1. Storage and supply 2. Absorbs TAG & cholesterol from

chylomicrons through lipoprotein lipase 3. Major storage site for triacylglcerol (TAG) 4. TAGs are continually in a state of flux-

constant lipolysis (hydrolysis) that is countered by constant re-esterification to form new TAG

5. Thus, the adipose tissue determines the level of circulating fatty acids

6. Adipocyte TAG sythesised from glucose influenced by insulin

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Fig 5-17 pg 156

Role of the Liver & Adipose Tissue in Lipid Metabolism- a combined effort

• Metabolism of triacylglycerol during fasting • During fasting the metabolism in tissues shifts.

– Adipocytes: • Lipolysis, release FA and glycerol into blood • FA are oxidised for energy by way of acetyl CoA

formation – Liver:

• Produces ketone bodies that serve as energy for muscle and brain

• Continues to synthesize VLDL & HDL • Glucose & FFA become major precursors for VLDL

synthesis

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Metabolism of Lipoproteins • Low-density lipoprotein (LDL)

– Transports cholesterol to tissues – Binds with LDL receptor on cells

• The LDL receptor: structure & genetic aberrations – Mutant cells can’t bind efficiently; synthesize

cholesterol to meet needs – Free cholesterol in the cell serves regulatory

functions

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COPYRIGHT CENGAGE LEARNING Fig5.20 pg 158

Metabolism of Lipoproteins

• High-density lipoprotein (HDL) – Removes unesterified cholesterol from

cells/other lipoproteins – Returns it to the liver for excretion in

bile (reverse cholesterol transport) – Binds to receptors on hepatic and extra-

hepatic cells – Cholesterol acyltransferase (LCAT)

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