Dietary Lipids

Question 1

Fats Overview

Answer 1

1. About 38% of the calories ingested in the USA today are fat. It has been stated that 30% represents the maximal percentage of fat in the optimal diet.
2. Functions of fat include the following:
   
   1. Storage of energy (9 Kcal/gram, as opposed to carbohydrates and proteins which yield 4 Kcal/gram); since fat’s don’t have any water in them, more ‘concentrated’
   2. Transport/Utilization of fat-soluble vitamins (vitamins D, E, K and A) and other fat-soluble substances; “DEKA”
   3. Essential fatty acids
   4. Insulation against heat loss
   5. Insulation against trauma
   6. Insulation against water loss
   7. Brain structure and nervous function
   8. Hormones
   9. Cell membranes
   10. Mothers milk
   11. Etc.
3. The predominant lipid in our diet is triacylglycerol (formerly called “Triglyceride”)
4. Body can create fat from suars; high carb diet leads to increase in triacylglycerol (TAG)

Question 2

Digestion of TAG

Answer 2

1. Lingual and gastric lipases hydrolyze primarily short and medium chain fatty acids from TAG
   
   1. Above lipases are most active during early childhood (human mother’s and cow’s milk have relatively high levels of short and medium chain fatty acids)*; assure that the nutrient is being absorbed by the young.
2. Note: short and medium chain fatty acids (C4-C12) are NOT emulsified by bile salts and are absorbed directly into the enterocytes. They are not packaged into chylomicrons, but are transported through the portal system bound to serum albumin. In the liver, these fatty acids are oxidized.
3. Lipase hydrolyzes fatty acids from positions 1 and 3, yielding 2-monoacylglycerol and (free) fatty acids
4. Colipase enhances pancreatic lipase catalytic activity; colipase is a coenzyme; made as a zymogen first
5. Cholesterol esterase liberates fatty acids (which are esterified to cholesterol) from cholesterol
6. Phospholipase A₂ liberates a fatty acid from a phospholipid, while lysophospholipase liberates the second fatty acid
   7.

Question 3

Bile

Answer 3

1. Cholic (Bile) acid can be covalently attached to either a molecule of glycine or taurine (an animo acid-like structure). Taurine-conjugated cholic acid is more hydrophilic than glycine-conjugated cholic acid.
2. Bile consists of the following:
   
   1. Water
   2. Cholesterol
   3. Bilins (bile pigments such as bilirubin, etc.)
   4. Bile acids/bile salts (sterol ring covalently attached to glycine or taurine)
   5. Phospholipids (primarily lecithin)
   6. Bicarbonate and other ions
   7. Etc.
3. Humans produce up to 800 milliliters of bile per day
   
   1. Bile functions in the emulsification of fats and fat-soluble vitamins
   2. Bile also functions in the elimination of waste products; xenobiotics are removed via bile since bile secrete into small instestine and eventually end up getting excrete
   3. Bile salts inhibit pancreatic lipase by blocking access of the enzyme to the substrate.
   4. Colipase acts to permit the lipase access to the substrate
   5. All of these are taking place in small intestine
4. Emulsification is promoted by bile salts, and also by:
   
   1. phospholipids (primarily lecithin); Lecithin has emulsification and lubricant properties
   2. Peristalsis (churning action)

Question 4

Hormonal control of digestion

Answer 4

1. Cholecystokinin (CCK) slows down the gastric motility so that only appropriate amount of food goes down the GI tract at a given time so as to properly digest everything piecemeal.
2. Chole (bile) + Cyst (bladder) + Kinin (to make move) –> Cholecystokinin; it induces gall bladder to secrete its content.
3. CCK also activates secretion from panreas of pancreatic enzymes

Question 5

Overview of Lipid Absorbtion

Answer 5

1. Lingual/salivary (and gastric) lipases hydrolyze short/medium chain TAG’s
2. Bile salts, manufactured in liver, emulsify fats.
3. Pancreatic lipase and colipase are secreted from pancreas; lipase hydrolyzes TAG’s to 2-monoacylglycerols
4. Bile salt micelles are formed
5. Micelles contain the following: TAG’s, monoacylglycerides, fatty acids, fat-soluble vitamins (A, D, E, K)
6. Micelles are absorbed into intestinal mucosal cells
7. TAG’s are re-formed in intestinal mucosal cells. Chylomicrons are assembled.
8. Chylomicrons consist of: TAG, cholesteryl esterified to free fatty acid, apoprotein, and phospholipids
9. Short and medium chain length fatty acids are not incorporated into chylomicrons, but are released into portal (liver) circulation as complexes of fatty acids/albumin
10. Chylomicrons are released by exocytosis into lymphatic vessels (lacteals), yielding a milky-colored fluid called chyle.
11. TAG’s in chylomicrons are hydrolyzed in skeletal muscle and adipose tissue capillaries by lipoprotein lipase.

Question 6

Absorption of lipids

Answer 6

1. Absorption of lipids in a micelle by a mucosal cell
   
   1. These micelles can go right through the water layer on top of the apical side of mucosal cell whereas other materials have harder time
2. The micelles are spherical particles. These particles are characterized by their possessing a hydrophilic exterior and a hydrophobic interior
3. The bile salts aid in the formation of the micelles.
4. The absorption of the fat-soluble vitamins (Vitamins D, E, K and A) requires the formation and absorption of micelles.
5. Micelles (tiny droplets) are formed in the intestinal lumen
   
   1. Micelles can contain:
      
      1. 2-monoacylglycerols and fatty acids produced from lipase digestion
      2. Cholesterol
      3. Lysophospholipids (phospholipids which have undergone enzymatic cleavage of an acyl residue)
   2. Fat-soluble vitamins (A,D,E,K)
   3. Bile salts
6. Micelles are absorbed by enterocytes through brush border membrane
7. Bile salts are not absorbed at this point; they are, however, resorbed in the ileum and recycled

Question 7

Synthesis of chylomicron inside enterocyte

Answer 7

1. Once inside the enterocyte, work our way back to generate TAGs again
2. TAG are resynthesized in enterocyte smooth endoplasmic reticulum
   
   1. Fatty acids are activated to fatty acyl CoA
   2. FA₁ CoA + 2-monoacylglycerol →diacylglycerol
   3. Diacylglycerol + FA₃ CoA →triacylglycerol

Question 8

Secretion, transport, and utilization of lipids

Answer 8

1. Chylomicrons are secreted by exocytosis into lymphatic chyle
2. Chylomicrons are the least dense of all the lipoproteins (combination of TAGs). They prevent coalescence of TAGs
3. Chyle flows into blood
4. Chylomicrons enter blood for many hours after digestion of dietary lipid
5. TAG found in chylomicrons is digested by lipoprotein lipase, which is located on basement membranes of capillary endothelial cells of adipose tissue, muscle, and other organs. The final product is glycerol and fatty acids
6. Fatty acids that enter muscle are oxidized to CO₂and H₂O
7. Fatty acids that enter adipose cells and liver can be esterified to TAG utilizing glycerol 3-P
8. Free fatty acids in the blood can become water soluble by complexing with albumin
9. Glycerol is metabolized by liver to glycerol 3-phosphate

Question 9

Steatorrhea

Answer 9

1. Steatorrhea can result from any condition that causes maldigestion or malabsorption.
2. The above conditions can include any of the following:
   
   1. Celiac disease
   2. Pancreatitis
   3. Cystic fibrosis
   4. Crohn’s disease
   5. Bile duct obstruction
   6. Shortened bowel secondary to surgical resection, etc.

Question 10

Free fatty acids

Answer 10

1. Free fatty acids (hydrolyzed TAG’s thus glycerol unit) can do any of the following:
   
   1. FFA can be oxidized for energy (in muscles)
   2. FFA can be transported with serum albumin (NOT a glycoprotein) to other cells
   3. FFA can be re-esterified in adipose cells and in liver to TAG’s; made in liver but stored in facts
2. Glycerol is converted in the liver to glycerol 3-phosphate, which can enter pathways of glycolysis or gluconeogenesis

Question 11

Chylomicron remnants

Answer 11

1. Chylomicron remnants (chylomicrons after removal of the TAG) enter liver through endocytosis, and are subsequently hydrolyzed.
2. Regulatory intestinal hormones:
   
   1. Secretin is stimulated by acidification (from the stomach). It stimulates the release from the liver and pancreas of a watery bicarbonate solution.
   2. Cholecystokinin (CCK) stimulates pancreas to secrete digestive enzymes. It also stimulates the gallbladder to contract, and the stomach to reduce its gastric motility.