Biochemistry Class: Lipid Chemistry

Study Notes

Lipids are a heterogeneous group of water-insoluble (hydrophobic) organic molecules
Lipids can be extracted from tissues using nonpolar solvents
Lipids are a major source of energy for the body
The digestive pathway of lipids begins in the stomach
Lipids are important for creating a barrier for the aqueous content of cells

Objectives: Explain the digestive pathway of lipids, discuss hormonal regulation of lipid digestion, and understand cystic fibrosis
Explain the digestive pathway of lipids in the stomach.
The digestion of lipids begins in the stomach, catalyzed by lingual lipase (glands at the back of the tongue) and gastric lipase (secreted by the gastric mucosa).
These enzymes are acid-stable, with pH optima of 4 to 6
Explain how these enzymes work on short- or medium-chain length fatty acids like milk fat
Explain how these enzymes work to break down molecules containing fatty acids

Lipase, assisted by colipase, is secreted by the pancreas to digest lipids
Colipase anchors lipase to the lipid-aqueous interface, restoring lipase activity when inhibited by bile acids
Orlistat, an antiobesity drug, inhibits gastric and pancreatic lipases, decreasing fat absorption and leading to weight loss

TAG degradation:
- Pancreatic lipase preferentially removes fatty acids at carbons 1 and 3.
- Hydrolysis products include 2-monoacylglycerol and free fatty acids
Cholesteryl ester degradation:
- Most dietary cholesterol is free (nonesterified).
- Cholesteryl esters are hydrolyzed by pancreatic cholesterol ester hydrolase (cholesterol esterase) to form cholesterol and free fatty acids.
- Bile salts increase cholesterol ester hydrolase activity
Phospholipid degradation:
- Pancreatic juice contains phospholipase A2, an enzyme activated by trypsin.
- Phospholipase A2 removes one fatty acid from carbon 2 of a phospholipid, requiring bile salts for optimal activity

Free fatty acids, free cholesterol, and 2-monoacylglycerol are primary products of lipid digestion.
Bile salts and fat-soluble vitamins (A, D, E, and K) form mixed micelles
Mixed micelles are disk-shaped clusters of amphipathic lipids, with hydrophobic groups inside and hydrophilic groups outside.
These micelles are soluble in the intestinal lumen
These lipid particles are absorbed by the brush border membrane of the enterocytes (mucosal cells)

Lipid malabsorption results in increased fat in the feces, called steatorrhea
Steatorrhea can occur due to disturbances in lipid digestion or absorption
Conditions like cystic fibrosis (CF) and shortened bowel can cause lipid malabsorption

Cells in the lower duodenum and jejunum secrete a peptide hormone called cholecystokinin (CCK) in response to lipids
CCK acts on the gallbladder to contract and release bile, and it also stimulates the exocrine pancreatic cells to secrete digestive enzymes
Secretin, another peptide hormone, regulates pancreatic secretion in response to acid in the duodenum
Secretin stimulates the pancreas to release bicarbonate-rich solutions, neutralizing the acidity of the intestinal contents

The diagram on diagram page 27 illustrates the key steps in lipid digestion from the gallbladder to the small intestine and its absorption into the cells.
The diagram on diagram page 21 shows lipid digestion and absorption, including the formation of chylomicrons for transport