Biochemistry Class: Lipid Chemistry

Biochemistry and Nutrition - Lipid Chemistry

• 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

Lipid Digestion and Objectives

• 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

Lipid Digestion in the Pancreas and Intestines

• 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

Lipid Degradation

• 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

Lipid Absorption

• 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

• 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

Control of Lipid Digestion

• 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

Other important notes

• 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