Lipid Metabolism Biochemistry MBBS 1st Year: Digestion, Absorption & Clinical Relevance

The Pathway Of Lipid Digestion

Dietary lipids primarily consist of triacylglycerols (TAGs), cholesterol esters, and phospholipids. Their digestion follows a specific path through the gastrointestinal tract.

• Mouth: Digestion is negligible. Lingual lipase is secreted but has little effect due to the short transit time of food.

• Stomach: Minimal digestion occurs. Gastric lipase, along with lingual lipase (acid-stable lipases), acts on short and medium-chain fatty acids. This is more significant in infants whose diet is milk-based.

• Small Intestine (Duodenum): This is the principal site for lipid digestion and absorption. The acidic chyme from the stomach triggers key hormonal responses.

Hormonal Regulation In The Duodenum

The arrival of food in the duodenum stimulates the release of two critical hormones from intestinal cells:

1. Cholecystokinin (CCK): This hormone has two major functions. It stimulates the gallbladder to release bile and triggers the pancreas to secrete digestive enzymes.
2. Secretin: This hormone causes the pancreas to release bicarbonate, which neutralizes the acidic chyme. This creates an optimal pH environment for pancreatic enzymes to function.                                                                          

Key Steps In Digestion

Emulsification: Increasing Surface Area

Emulsification is the process where large fat globules are broken down into smaller droplets. This is not chemical digestion but a physical dispersion that dramatically increases the surface area available for enzymes to act upon. Bile Salts, released in bile, are essential for this process due to their detergent-like action, which reduces surface tension.

Enzymatic Digestion

The pancreas releases a trio of powerful enzymes that chemically digest the emulsified lipid droplets.

• Pancreatic Lipase: This is the major enzyme in lipid digestion. It hydrolyzes triacylglycerols at the C1 and C3 positions, yielding two free fatty acids and a 2-monoacylglycerol.
• Cholesterol Esterase: This enzyme breaks down cholesterol esters into free cholesterol and a fatty acid.
• Phospholipase A2: This enzyme acts on phospholipids, cleaving the fatty acid at the C2 position to produce a free fatty acid and a lysophospholipid.

Absorption And Transport Of Lipids

Mixed Micelle Formation

The products of digestion (free fatty acids, monoacylglycerols, cholesterol, lysophospholipids) are insoluble in water. To be absorbed, they are packaged into Mixed Micelles. These are small, water-soluble aggregates with Bile Salts forming the outer layer and the hydrophobic lipid products in the core.

Absorption Into Intestinal Cells

The Mixed Micelles travel to the surface of the intestinal cells (enterocytes). The lipid contents are then absorbed from the micelle into the cell via Simple Diffusion, a process that does not require energy or a carrier protein.

Re-synthesis And Chylomicron Formation

Inside the enterocyte, a unique process called re-synthesis occurs:

1. Monoacylglycerols and fatty acids are re-formed into triacylglycerols.

2. Cholesterol is re-esterified to form cholesterol esters.

3. Lysophospholipids are converted back into phospholipids.

These newly re-synthesized lipids, being insoluble, are packaged into a special lipoprotein particle called a Chylomicron. This particle consists of a lipid core (mainly TAGs) and a protein coat (ApoB-48), making it water-soluble.

Chylomicrons are then secreted from the enterocytes into the lymphatic system, bypassing the liver initially. They travel through the thoracic duct to enter the bloodstream, delivering lipids to the rest of the body.

Disorders Of Lipid Absorption

Impaired lipid digestion or absorption leads to malabsorption, characterized by the presence of undigested fat in faeces, a condition known as Steatorrhea. Common causes include:

• Bile Flow Obstruction: Conditions like gallstones or tumors can block the flow of bile, preventing Emulsification and Mixed Micelle formation.

• Pancreatitis: Inflammation of the pancreas can impair the secretion of essential digestive enzymes like Pancreatic Lipase, leading to incomplete fat digestion.