Lecture 27 & 28

Digestion of lipids and nutritional importance of lipids I & II

Dr. S. Annie Jeyachristy
Lecturer in Biochemistry Faculty of Medicine AIMST University

OBJECTIVES
Lecture 27 to 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 occurring

fatty acids and the relative proportion of fatty acids in

lipids.

LEARNING OUTCOMES
Lecture 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.

LIPIDS
Heterogeneous 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.

CLASSIFICATION of LIPIDS
LIPIDS

SIMPLE LIPIDS

COMPOUND LIPIDS PHOSPHOLIPIDS LECITHIN

DERIVED LIPIDS ALCOHOL

FATS & OIL SIMPLE MIXED WAXES

FATTY ACIDS STEROLS

CEPHALIN
ISOPRENOIDS PLASMALOGEN SPHINGOMYELIN CAROTENOIDS GLYCOLIPIDS CEREBROSIDES GANGLIOSIDES SULFOLIPIDS TERPENOIDS

CLASSIFICATION of FATTY ACIDS

Fatty acids

STRAIGHT CHAIN

CYCLIC PROSTAGLANDINS

SATURATED UNSATURATED MONOUNSATURATED POLYUNSATURATED OMEGA 3 OMEGA 6

THROMBOXANES

CisTrans-

Lipids/ Fat

In food

In body

Energy

Essential Nutrient

Flavor

Adipose Tissue

Cell Membrane

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.

Food Sources of Fat Animal Fats Meat Fat (bacon, sausage.) Dairy Fats and products (cream, butter, cheese..) Egg yolk Plant Fats Monounsaturated, polyunsaturated Fatty acid Vegetable oil (safflower, corn, soybean, cottonseed, olive oil)

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..

DIGESTION, ABSORPTION, SECRETION AND UTILIZATION OF DIETARY LIPIDS

Ingestion of lipids by adults 60-80g per day

More than 90% is normally triacylglycerol

Remaining consists of cholesterol, cholesteryl esters,

phospholipids, unesterified (free) fatty acids. Digestion of lipids begins in stomach.

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 (<12 carbon) Importance in Neonates (to digest milk fat)

Cystic fibrosis (individuals with pancreatic insufficiency- lack pancreatic

lipase)

Digestion of lipids in small intestine

Emulsification of lipids Emulsification increases the surface area of the hydrophobic lipid droplets so that the digestive enzymes, can work at the interface of the droplet and the surrounding aqueous solution can act effectively. Bile salts derivative of cholesterol, made in liver, stored in gall bladder, association with glycine or taurine Mechanical mixing due to peristalsis

Bile Acids
1. The end products of cholesterol utilization are the bile acids, synthesized in the liver. Primary bile acids in human bile are 1. chenodeoxycholic acid (45%) and 2. cholic acid (31%). Secondary bile acids, 1. deoxycholate (from cholate) and 2. lithocholate (from chenodeoxycholate). Conjugation with glycine or taurine before their secretion into the bile yield 1. Glycocholic acid 2. Taurocholic acid

2.

3.

4.

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

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 molecules with 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.

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 Colipase Also secreted by pancreas and binds pancreatic lipase at a ratio of one to 2 fatty acids + Mono glycerides

one.
Anchors at lipid aqueous interface. Procolipase

colipase

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

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
Lysophosphatidylcholine

fatty acid + lysophosphatidyl choline

fatty acid + Glycerylphosphoryl choline

Regulation of lipid digestion - Hormonally controlled

Cholecystokinin Secretin 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 action

Acts 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.

Secretin Small 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 pancreatic

enzymes.
Chyme semifluid mass of partially digested food that passes from the stomach to the duodenum

Absorption of lipids by intestinal mucosal cells

Free fatty acids

Free cholesterol
2-monoacyl glycerol
Primary products of lipid digestion

Together with

Bile salts

Mixed micelles
Disc shaped clusters of amphipathic lipids (hydrophilic groups outside and hydorphobic groups inside)

Brush border membrane of intestinal mucosal cells

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

Resynthesis of triacylglycerols and cholesteryl esters

In enterocytes

Mixture of lipids (absorbed)

Activation Fatty acids Thiokinase (Fatty acyl CoA synthetase) Conversion Fatty acyl CoA derivatives

For biosynthesis of complex lipids

Migrates to ER

Monoacylglycerol
Monoacylglyceol acyl transferase Diacylglycerol acyl transferase Lysophospholipids Acyl transferases Cholesterol Acyl CoA cholesterol acyl transferase

Triacylglycerol

Phospholipids Cholesteryl ester

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 dietary cholesterol is absorbed. Dietary fat increases cholesterol absorption Fiber (especially soluble fiber) and phytosterols decrease cholesterol absorption

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

triglycerides

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 disorder Familial lipoprotein lipase deficiency (Type I hyperlipoproteinemia) resulting in massive chylomicronemia

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-3phosphate 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)

Transportation of lipids Lipids are transported in the plasma as lipoproteins

Source Chylomicrons Intestine Destination Many organs Major lipids Triglycerides, other lipids Triglycerides, Cholesterol Functions Deliver lipids of dietary origin to body cell. Deliver endogenously produced triglycerides to body cells. Deliver endogenously produced cholesterol to various organs. Remove and degrade Cholesterol.

VLDLs

Liver

Many organs

LDLs

Intraviscular removal of triglycerides from VLDL Liver and intestine

Blood vessels, Liver

Cholesterol

HDLs

Liver and steroidhormone-producing glands

Cholesterol