Lipid Chemistry Lecture Notes

Lipid Chemistry Lecture Notes

• Lipids are a diverse group of hydrophobic organic molecules. They can be extracted from tissues using nonpolar solvents.
• Lipids function as a major energy source for the body. They also form a hydrophobic barrier which helps to partition the intracellular components of cells.
• Some fat-soluble vitamins act as regulatory or coenzyme factors. Prostaglandins and steroid hormones play roles in body homeostasis.
• Lipid metabolism imbalances can cause atherosclerosis and obesity.
• Dietary lipids are mostly triacylglycerols (TAGs). These also include cholesterol, cholesterol esters, phospholipids, and unesterified fatty acids.
• Lipid digestion begins in the stomach with lingual and gastric lipase. These enzymes are acid stable, with pH optima of 4-6. They hydrolyze short- or medium-chain TAGs (like those in milk fat).

Specific Lecture Objectives

• Explain lipid digestion pathway
• Discuss hormonal regulation of lipid digestion
• Understand the cause of cystic fibrosis

Lipid Digestion in the Stomach

• Lipid digestion starts in the stomach.
• Lingual lipase and gastric lipase initiate the process in the stomach.
• These lipases are acid stable with pH optima ranging from 4 to 6.
• These enzymes hydrolyze TAG molecules with short or medium chain fatty acids.

Acid Lipases

• These lipases are particularly important in neonates, where milk fat is the main source of calories.
• Acid lipases become vital in individuals with pancreatic insufficiency, including those with cystic fibrosis.

Cystic Fibrosis (CF)

• Autosomal recessive disorder caused by mutations impacting the CFTR protein which is a chloride channel in the epithelium.
• Defective CFTR leads to decreased chloride secretion and increased sodium and water reabsorption.
• These abnormalities cause thick, sticky mucus buildup in the airways and pancreas. This leads to pancreatic insufficiency and frequent infections.
• Treatment includes enzyme replacement, supplementation of fat-soluble vitamins (like vitamin D), and water-soluble vitamins.

Emulsification in the Duodenum

• Emulsification increases the surface area of hydrophobic lipid droplets.
• Bile salts, produced in the liver and stored in the gallbladder, are emulsifying agents. They are cholesterol derivatives.

Degradation of Dietary Lipids by Pancreatic Enzymes

• Pancreatic lipase preferentially removes fatty acids at carbons 1 and 3 of TAGs.
• The primary products of hydrolysis are 2-monoacylglycerol and free fatty acids.
• Colipase, also secreted by the pancreas, improves lipase activity and binds the enzyme to the lipid-aqueous interface, which greatly enhances the functionality.
• Orlistat, an antiobesity drug, inhibits gastric and pancreatic lipases, reducing fat absorption.

Cholesteryl Ester Degradation

• Most dietary cholesterol is in a free (nonesterified) form, with 10-15% esterified.
• Pancreatic cholesteryl ester hydrolase (cholesterol esterase) hydrolyzes cholesteryl esters, producing cholesterol and free fatty acids.
• Bile salts enhance the activity of cholesterol ester hydrolase.

Phospholipid Degradation

• Pancreatic juice contains proenzyme of phospholipase A2. This enzyme is activated by trypsin and requires bile salts for optimal activity.
• Phospholipase A2 removes a fatty acid from carbon 2 of phospholipids.

Lipid Absorption by Intestinal Mucosal Cells

• Free fatty acids, free cholesterol, and 2-monoacylglycerol are the primary products of lipid digestion in the jejunum.
• Bile salts and fat-soluble vitamins (A, D, E, K) form mixed micelles.
• Mixed micelles are disk-shaped clusters of amphipathic lipids with their hydrophobic groups inside and hydrophilic groups on the outside. They aid in lipid absorption in the intestinal lumen.
• These micelles are absorbed by the brush border membrane of the enterocytes (intestinal cells).
• The absorbed fats are combined with cholesterol and proteins in the intestinal cells to form chylomicrons which move into the lymphatic system then the circulatory system.

Lipid Malabsorption

• Lipid malabsorption, often marked by increased lipids and fat-soluble vitamins in the feces, is referred to as steatorrhea.
• Steatorrhea arises from disturbances in lipid digestion or absorption.
• Causes include cystic fibrosis (CF), reduced surface area of the intestinal tract due to bowel disease, or some other conditions.

Lipid Digestion Summary

• Lipids are a heterogeneous group of hydrophobic molecules
• Digestion begins in the stomach with lingual and gastric lipase
• Emulsification increases the surface area for enzymes
• Pancreatic lipases and Cholesteryl Ester Hydrolase (Cholesterol Esterase) further degrade lipids
• The products are absorbed by enterocytes through mixed micelles
• Hormones (CCK and Secretin) regulate these processes.

This quiz covers the essential aspects of lipid chemistry, including lipid digestion, metabolism, and the role of lipids in energy storage and cellular functions. Additionally, it addresses the hormonal regulation of lipid processes and the impact of dietary lipids on health. Test your knowledge on these fundamental concepts of lipid science.