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Lipid Metabolism

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Lipid Metabolism

Prof. Dr. Zeliha Büyükbingöl

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Lipids

The term lipids includes a divers group of structurally distinct hydrophobic and amphipathic molecules.

Most of the lipids found in the body fall into the categories of:

Fatty acids

Triacylglycerols

Glycerophospholipids and sphingolipids Eicosanoids

Cholesterol Bile salts

Steroid hormones

Fat-soluble vitamins

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Biological Functions

 Lipids are synthesized in the body using complex biosynthetic pathways.

 Lipids play important role in the body than previously believed.

 Lipids play the role of storage of energy

 forming cell membranes

 intracellular signalling

 hormonal regulation

 enzyme cofactors

 maintenance of body temperature …

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PLASMA MEMBRANES

 All mammalian cells are enclosed by a plasma membrane which is composed of various lipids, proteins and carbohydrates.

 Each layer of plasma membrane lipid bilayer is formed primarly by phospholipids. Additionally, cholesterol maintains membrane fluidity.

 Membranes are generally %40-%50 protein. Protein and lipid

composition is unique for each membrane.

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Fluid mosaic model

 The assembly of proteins and lipids into a membrane creates a fluid mosaic model.

 Proteins and lipids undergo two dimensional lateral diffusion in

membrane. Transverse diffusion is energetically unfavorable, exept flippase process.

 Fluidty is affected:- long chain saturated fatty acids interact strogly and

reduce fluidity, - double bonds increase fluidity,-cholesterol prevents

movement of fatty acid chains and reduces fluidity,- fluidity increases

with temperature,

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LIPID METABOLISM

is the synthesis and

degradation of lipids in cells

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OVERVIEW

Exogenous (dietary) & Endogenous Lipids

Digestion and Transport of Dietary Lipids

Lipoproteins

Synhesis of Fatty Acids (FA), Triacylglycerols (TAG) and Phospholipids

Triacylglycerol Mobilization and Fatty Acid Oxidation

Cholesterol Metabolism

Ketone Bodies

Bile salts and Bile Acids

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Dietary lipids (fats): Triacylglycerols (TAGs) are the major fat in the

human diet (90%). In addition to TAGs, free fatty acids, phospholipids

, cholesterol and cholesterol esters are present in the foods we eat.

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Digestion of Triacylglycerols and the Other Fats

Lingual lipase/ gastric lipase (limited digestion)

Action of bile acid : In the intestine, the fats are emulsified by bile salts.

Action of pancreatic lipase: In the intestine pancreatic lipase-

together with colipase- hydrolyses fatty acids of all chain lengths from position 1 and 3 of the glycerol moiety of the TAG, producing free fatty acids and 2-monoacyl glycerol.

 The pancreas also produces esterases that remove fatty acids from

compounds such as cholesterol esters and phospholipase A2 that

digests phospholipids to a free fatty acid and lysophospholipid.

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ABSORPTION OF DIETARTY LIPIDS

In the small intestine, dietary fat emulsified by bile salts, which are synhesized in the liver and stored in the gall-bladder. The products of enzymatic digestion form micells with bile acids in the intestinal lumenThe micelles interact with with the enterocyte membrane and allow diffusion of the lipid-soluble components acros sthe membrane. The bile acids do not enter enterocyte , they remain in the intestinal lumen travel down and are reabsorbed sent back to liver by enterohepatic circulation. Short and medium chained fatty acids do not require bile salts for their absorption. Within the intestinal epithelial cells resynthesize TAG from free fatty acids and 2-monoacylglycerol and package with apolipoprotein , phospholips, and cholesterol esters into a water soluble lipoprotein particle called chylomicron (CM). The cylomicrons are secreted into the lymph and eventually into the circulation where they can distrubute dietary lipids to all tissues.

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Other Plasma Lipoproteins

Chylomicron: density <0.95g/mL Transports dietary triacylglycerol to peripheral tissues

VLDL: density 0.95–1.006 g/mL Transports liver derived TAG to extrahepatic tissues. They are second -after CM- in the percentage triglyceride content.

IDL: density1.006–1.019g/mL

LDL: density1.019–1.063g/mL is the last VLDL remnant, delivers cholesterol from liver to extrahepatic tissues, called ‘bad cholesterol’

HDL: density>1.063g/mL Takes up cholesterol from peripheric tissues and

 returns it to liver, called ‘good cholesterol’

 High LDL, VLDL and triglyceride levels are associated with a high risk of cardiovascular disease. High HDL is correlated with reduced cholesterol levels, and a lower cardiovascular risk. Dyslipidemia is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein level that contributes to the

development of atherosclerosis.

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