Lecture 27 & 28_Digestion of Lipids and Nutritional Importance of Lipids

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    Digestion of lipids and nutritionalimportance of lipids I & II

    Lecture 27 & 28

    Dr. S. Annie JeyachristyLecturer in Biochemistry

    Faculty of MedicineAIMST University

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    Lecture 27to discuss digestive enzymes, their action on dietary

    lipids, absorption of lipids and disorders of digestion

    and absorption.

    Lecture 28

    to discuss nutritional role of lipids, naturally occurringfatty acids and the relative proportion of fatty acids in

    lipids.

    OBJECTIVES

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    LEARNING OUTCOMESLecture 27

    Describe the digestion, absorption, secretion and utilization of dietary

    lipids.

    Describe the role of enzymes in the digestion of lipids in mouth, stomach

    and intestine.

    Describe the causes, symptoms and treatment of steatorrhea.

    Explain the general malabsorption disorders associated with lipids.

    Lecture 28

    Provide the sources of lipids and the relative proportion of fatty acids in

    lipids.

    Name the naturally-occurring fatty acids.

    Give the values and reasons for the recommended intake of fats.

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    LIPIDSHeterogeneous group of water-insoluble (hydrophobic)

    organic molecules

    Can be extracted from tissues by nonpolar solvents

    Generally found compartmentalized because of its

    insoluble nature. Eg. membrane associated lipids or

    droplets of triacylglycerol in adipocytes, protein associated

    lipids as lipoproteins for transport of lipids.

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    CLASSIFICATION of LIPIDSLIPIDS

    SIMPLE LIPIDS COMPOUND LIPIDS DERIVED LIPIDS

    FATS & OIL

    WAXES

    PHOSPHOLIPIDS

    GLYCOLIPIDS

    LECITHIN

    CEPHALIN

    PLASMALOGEN

    SPHINGOMYELIN

    CEREBROSIDES

    GANGLIOSIDES

    ALCOHOL

    FATTY ACIDS

    STEROLS

    ISOPRENOIDS

    TERPENOIDS

    CAROTENOIDS

    SULFOLIPIDS

    SIMPLE

    MIXED

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    CLASSIFICATION of FATTY ACIDSFatty acids

    SATURATED

    UNSATURATED

    MONOUNSATURATED

    POLYUNSATURATED

    PROSTAGLANDINS

    THROMBOXANES

    STRAIGHT CHAIN CYCLIC

    OMEGA 3

    OMEGA 6

    Cis-

    Trans-

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    Lipids/ Fat

    In food In body

    Energy EssentialNutrient

    Flavor AdiposeTissue CellMembrane

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    Functions

    Major source of energy for the body

    Also provides hydrophobic barrier that permits

    partitioning of the aqueous contents of cells and

    subcellular structures.

    Fat-soluble vitamins have regulatory or coenzyme

    functions.

    Prostaglandins and steroid hormones plays role in

    maintaining body homeostasis.

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    Food Sources of Fat

    Animal Fats

    Meat Fat (bacon, sausage.)

    Dairy Fats and products (cream, butter, cheese..)

    Egg yolk

    Plant Fats

    Monounsaturated, polyunsaturated Fatty acidVegetable oil (safflower, corn, soybean, cottonseed,

    olive oil)

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    Characteristics Of Food Fat Sources

    Visible fat

    Butter, margarin, salad oils and dressing,shirteninig

    fat meat

    Invisible fat

    Cheese, cream portion of homogenised milk, egg

    yolk, nuts, seeds, olives..

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    DIGESTION, ABSORPTION, SECRETION AND UTILIZATION

    OF DIETARY LIPIDS

    Ingestion of lipids by adults60-80g per day

    More than 90% is normally triacylglycerolRemaining consists of cholesterol, cholesteryl esters,

    phospholipids, unesterified (free) fatty acids.

    Digestion of lipids begins in stomach.

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    Digestion of lipids in stomach

    Lingual lipase (originates from the glands at the back of the tongue)

    Gastric lipase (secreted by gastric mucosa)

    Both are acid stable lipases, with pH optimum of pH4 to pH8

    Act on triacylglycerols with short and medium-length fatty acids (

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    Digestion of lipids in small intestine

    Emulsification of lipids

    Emulsification increases the surface area of the hydrophobic lipid droplets sothat the digestive enzymes, can work at the interface of the droplet and the

    surrounding aqueous solution can act effectively.

    Bile saltsderivative of cholesterol, made in liver, stored in gall bladder,

    association with glycine or taurine

    Mechanical mixing due to peristalsis

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    Bile Acids

    1. The end products of cholesterol utilization are the bile acids, synthesized in theliver.

    2. Primary bile acids in human bile are

    1. chenodeoxycholic acid (45%) and

    2. cholic acid (31%).

    3. Secondary bile acids,

    1. deoxycholate (from cholate) and

    2. lithocholate (from chenodeoxycholate).

    4. Conjugation with glycine or taurine before their secretion into the bile yield

    1. Glycocholic acid

    2. Taurocholic acid

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    Micelles: tiny emulsified fat packets that can enter intestinal cells (enterocytes)

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    Lipid (fats and oils) is insoluble in water (hydrophobic).

    Lipids tend to coalesce into larger droplets which reduces the surface

    area for digestion.

    The hydrophobic lipid is only accessible to the water soluble lipases

    at the interface between lipid and water.

    To increase the access (increased surface area) and rate of lipid

    digestion the lipid droplet must be broken up.

    Bile salts secreted from the liver (via gallbladder) have moleculeswith a combination of hydrophobic and (lipophilic) hydrophilic

    regions.

    Bile salts break up the lipid droplet into many smaller droplets

    thereby increasing the surface area of lipid-water access.

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    Enzymatic degradation of lipids by pancreatic enzymes

    Triacylglycerol degradation

    Pancreatic lipase

    Triacylglycerol molecules are too large

    Cannot be taken up efficiently by the mucosal cells of the intestinal villi

    Removes fatty acid at C1 and C3.

    Products are 2 monacylglycerol and free fatty acids

    Triglycerides 2 fatty acids + Mono glycerides

    Colipase

    Also secreted by pancreas and binds pancreatic lipase at a ratio of one to

    one.

    Anchors at lipid aqueous interface.

    Procolipase

    colipase

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    Cholesteryl ester degradation

    Mostly in free form ; 10-15% in esterified form

    Cholesteryl esters are hydrolysed by pancreatic cholesterol ester

    hydrolase (cholesterol esterase)

    Products are cholesterol and free fatty acids

    Cholesteryl esterase activity is greatly increased in the presence of bile

    salts

    Cholesteryl esters

    fatty acids + cholesterol

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    Phospholipid degradation

    Phospholipids are hydrolysed by phospholipase A2.Pancreatic juice is rich in phospholipase A2; activated by trypsin;

    requires bile salts for optimum activity

    Products are lysophospholipid and free fatty acid

    Lysophospholipase removes another fatty acid and the product is

    glycerylphosphoryl base.

    Glycerylphosphoryl base may be excreted in feces, further degraded or

    absorbed.

    Phosphatidyl choline fatty acid +lysophosphatidyl choline

    Lysophosphatidylcholine

    fatty acid +Glycerylphosphoryl choline

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    Regulation of lipid digestion - Hormonally controlled

    CholecystokininSecretin

    Cholecystokinin (formerly called as pancreozymin)

    Small peptide hormone

    Produced by mucosal cells of jejunum and lower duodenum

    Secreted in response to presence of lipids and partially digested proteins

    entering upper small intestine

    Mode of actionActs on gall bladder causing contraction and release of bile

    Acts on exocrine cells of pancreas and aids release of digestive enzymes

    Decreases gastric motility resulting in slower release of gastric contents

    into the small intestine.

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    SecretinSmall peptide hormone

    Produced by intestinal cells

    Secreted in response to low pH of the chyme entering the intestine.

    Mode of action

    Acts on pancreas and liver resulting in release of watery solution rich in

    bicarbonate that helps in neutralization of pH of the intestinal contents.

    Maintains the appropriate pH for enzymatic digestion by pancreaticenzymes.

    Chymesemifluid mass of partially digested food that passes from the stomach to the duodenum

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    Absorption of lipids by intestinal mucosal cells

    Free fatty acids

    Free cholesterol

    2-monoacyl glycerol

    Bile salts Mixed micelles

    Brush border membrane

    of intestinal mucosal cells

    Together

    with

    Primary products

    of lipid digestion

    Disc shaped clusters of

    amphipathic lipids(hydrophilic groups

    outside and hydorphobic

    groups inside)

    This membrane is separated from the liquid contents of the intestinal lumen by an

    unstirred water layer that is partially miscible with the bulky fluid.

    Hydrophilic surface of micelles facilitates transport of hydrophobic lipids through

    unstirred water layer for absorption

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    Resynthesis of triacylglycerols and cholesteryl esters

    Mixture of lipids

    (absorbed)For biosynthesis of complex lipids

    Migrates to

    ER

    In enterocytes

    Fatty acids Fatty acyl CoA derivatives

    Thiokinase (Fatty acylCoA synthetase)

    Activation

    Conversion

    Monoacylglycerol TriacylglycerolMonoacylglyceol acyl transferase

    Diacylglycerol acyl transferase

    Lysophospholipids PhospholipidsAcyl transferases

    Cholesterol Cholesteryl esterAcyl CoA cholesterol acyl

    transferase

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    Long- chain fatty acids

    Resynthesis in the similar fashion

    Small- and Medium- chain fatty acids

    Need not form mixed micelles for absorption by the intestinal mucosa.

    (dietary therapy for individuals with malabsorption of other lipids)

    Not converted to CoA derivatives and not reesterified

    They are released into portal circulation and are carried by serum albumin to

    liver.

    Cholesterol and other sterols are poorly absorbed. Overall, about 50% of dietarycholesterol is absorbed.

    Dietary fat increases cholesterol absorption

    Fiber (especially soluble fiber) and phytosterols decrease cholesterol absorption

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    Secretion of lipids from enterocytes

    Newly synthesized triacylglycerols and cholesteryl esters are hydrophobic and

    aggregate in aqueous environment.

    Hence, they are packaged as lipid droplets surrounded by thin layer of

    phospholipids, unesterified cholesterol and protein molecule (apolipoprotein B48)

    - chylomicrons

    This thin layer stabilizes the lipid particle and increases solubility preventing

    coalescing of multiple particles.Chylomicrons are released by exocytosis from enterocytes into lacteals (lymphatic

    vessels villi of small intestine)

    Enter thoracic duct and then to the left subciavian vein and finally enter into blood

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    triglycerides

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    Utilization of lipids by tissues

    Triacylglycerol in chylomicrons are broken down in the capillaries of skeletal

    muscle , adipose tissues, heart, lung, kidney and liver.

    Triacylglycerol is degraded by to free fatty acids and glycerol by lipoprotein

    lipase.

    Lipoprotein lipase is synthesized primarily by adipocytes and muscle cells and is

    secreted and associated with the luminal surface of the endothelial cells of the

    capillary beds of the peripheral tissues

    Deficiency of lipoprotein lipase or its coenzyme apo C-II leads to rare, autosomal

    recessive disorderFamilial lipoprotein lipase deficiency (Type I

    hyperlipoproteinemia) resulting in massive chylomicronemia

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    Fate of free fatty acids

    From the hydrolysis of triacylglycerols directly enters mucosal cells or

    adipocytes.

    Or transported in the blood with serum albumin until taken up by cells.

    Most cells oxidize fatty acids for energy

    Adipocytes reesterifies to produce triacylglycerol for storage purpose.

    Fate of glycerol

    Released from triacylglycerol is almost used by liver to produce glycerol-3-

    phosphate which enters glycolysis or gluconeogenesis (oxidation of

    dihydroxyacetone phosphate)

    Fate of chylomicron components

    Chylomicron remnants bind to receptors in liver and then endocytosed.

    Defect in chylomicron remnant removal by liver resulting in accumulation of

    chylomicron remnants in plasma leads to Familial dysbetalipoproteinemia (Type

    III hyperlipoproteinemia)

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    Source Destination Major lipids Functions

    Chylomicrons Intestine Many organs Triglycerides, other

    lipids

    Deliver lipids of

    dietary origin to

    body cell.

    VLDLs Liver Many organs Triglycerides,

    Cholesterol

    Deliver

    endogenously

    produced

    triglycerides to

    body cells.

    LDLs Intraviscular

    removal of

    triglycerides from

    VLDL

    Blood vessels, Liver Cholesterol Deliver

    endogenously

    produced

    cholesterol to

    various organs.

    HDLs Liver and intestine Liver and steroid-

    hormone-producing

    glands

    Cholesterol Remove and

    degrade

    Cholesterol.

    Lipids are transported in the plasma as lipoproteins

    Transportation of lipids