Lipid Metabolism Overview

Water-insoluble molecules like fats, oils, and waxes that play crucial roles in energy storage, structural integrity, and cellular signaling.

Fatty acids are long chains of carbon atoms with a carboxyl group at one end. They are the building blocks of many other lipids.

The primary form of energy storage in the body. They consist of three fatty acids attached to a glycerol molecule.

They form the structural backbone of cell membranes and act as signaling molecules. Composed of a phosphate group, a glycerol molecule, and two fatty acids.

A type of lipid that acts as a structural component of cell membranes and is a precursor to steroid hormones like cholesterol.

Lipases are enzymes that break down fats (lipids) into smaller components. They are crucial for digesting dietary fats, primarily in the small intestine.

Lipase is a type of enzyme that specifically breaks down triglycerides (TAGs) into fatty acids (FAs) and 2-monoacylglycerol (2MAG). It removes fatty acids from the 1st and 3rd positions of the triglyceride molecule.

Colipase is a protein that helps lipase work efficiently. It binds to lipase, anchors it to the surface of fat droplets, and helps position lipase so it can break down fats.

Cholesterol esterase is an enzyme that breaks down cholesterol esters, which are a form of cholesterol bound to a fatty acid, into free cholesterol and a fatty acid.

Phospholipase A2 (PLA2) is an enzyme that breaks down phospholipids, which are important components of cell membranes, into fatty acids and lysophospholipids. It removes a fatty acid from the second position of the phospholipid molecule.

Bile acids are substances produced by the liver that help in the digestion of fats. They act as detergents, breaking down large fat droplets into smaller ones, making them easier for lipases to access.

Orlistat is a drug used to treat obesity. It works by blocking the activity of both gastric and pancreatic lipases, reducing the absorption of fats from the diet.

The digestion of lipids occurs in the mouth, stomach, and primarily in the small intestine. Different enzymes, including lingual lipase, gastric lipase, pancreatic lipase, and cholesterol esterase, contribute to the breakdown of fats.

Bile salts are the ionized form of bile acids, which are crucial for lipid digestion. They are produced in the liver, stored in the gallbladder, and synthesized from cholesterol. Chemically, they consist of a sterol ring, a side chain, and either glycine or taurine attached via an amide linkage.

Bile salts play a vital role in emulsifying lipids, breaking down large fat droplets into smaller ones. This increases the surface area for the action of pancreatic lipases, which are enzymes responsible for digesting fats.

Bile salts activate pancreatic lipases, enzymes that break down fats into smaller components that can be absorbed. This activation is essential for efficient lipid digestion.

Micelles are tiny, spherical structures formed in the small intestine that contain bile salts and the products of fat digestion. This crucial structure transports digested fats to the intestinal epithelial cells for absorption.

Short-chain fatty acids (SCFAs) and medium-chain fatty acids (MCFAs) are absorbed directly into the intestinal epithelial cells without needing micelles for transport. They are smaller and more soluble in water than long-chain fatty acids.

Lipid malabsorption is a condition where the body cannot properly absorb dietary fats. This can lead to deficiencies in essential fatty acids and fat-soluble vitamins. It can be caused by impaired bile secretion, pancreatic juice secretion, or defective intestinal mucosal cell function.

The products of lipid digestion, including fatty acids, cholesterol, and monoglycerides, are re-synthesized into triglycerides, phospholipids, and cholesterol esters within the intestinal epithelial cells. This process allows for the efficient packaging of lipids into chylomicrons for transport.

Chylomicrons are tiny particles responsible for transporting newly re-synthesized lipids from the intestinal epithelial cells to the bloodstream for delivery to various tissues throughout the body.

Cholecystokinin (CCK) is a hormone that stimulates the contraction of the gallbladder and the secretion of pancreatic enzymes. This process aids in the digestion of fats by releasing bile and digestive enzymes.

Secretin is a hormone that stimulates the release of bicarbonate from the pancreas. This bicarbonate neutralizes the acidic chyme from the stomach, creating an optimal pH for the proper functioning of pancreatic lipases.

Chylomicrons are lipoprotein complexes primarily composed of triglycerides (TAG) and cholesterol that are synthesized by the intestinal cells.

Lipoprotein complexes are spherical particles composed of proteins and lipids. They act as carriers for lipids in the bloodstream.

Apolipoproteins are protein molecules that are associated with lipoprotein complexes. They play various roles, including structural support, receptor binding, enzyme activation, and lipid exchange.

Nascent chylomicrons are newly synthesized chylomicrons that are secreted from the intestinal cells into the lymph.

Mature chylomicrons are formed when nascent chylomicrons acquire apolipoproteins CII and E from HDL in the bloodstream.

Lipoprotein lipase (LPL) is an enzyme responsible for the breakdown of triglycerides in chylomicrons into free fatty acids and glycerol during their circulation.

Chylomicron remnants are leftover parts of chylomicrons after LPL-mediated breakdown of triglycerides. They are transported back to the liver for recycling.

Apo B-48 and Apo E are apolipoproteins that are recognized by receptors on hepatocytes, facilitating the uptake of chylomicron remnants by the liver.

Nascent chylomicrons are first secreted into the lymphatic system (specifically the lacteals within intestinal villi) and then enter the bloodstream.

In the bloodstream, nascent chylomicrons acquire additional proteins, apoCII and apoE, from high-density lipoproteins (HDL).

Mature chylomicrons, now containing apoB48, apoCII, and apoE, circulate in the blood and reach capillary beds.

ApoCII, a protein present in mature chylomicrons, activates lipoprotein lipase (LPL) located on the surface of capillary walls.

Activated LPL breaks down the triglycerides (TAG) within mature chylomicrons into glycerol and free fatty acids (FFA).

After releasing most of their TAGs, chylomicrons become smaller and are now known as chylomicron remnants.

Chylomicron remnants return apoCII to HDL, and then travel to the liver.

Chylomicron remnants are recognized by receptors on liver cells, leading to receptor-mediated endocytosis.

Lipoprotein lipase (LPL) is an enzyme that breaks down triglycerides (TAG) in chylomicrons and very-low-density lipoproteins (VLDL). It is mainly found in capillary walls of adipose tissue, muscle cells, and lactating mammary glands.

LPL is activated by apoCII, a protein present in both chylomicrons and VLDL. It binds to the capillary walls via heparan sulfate.

The main substrates for LPL are triglycerides (TAGs) in chylomicrons and VLDL. It breaks down TAGs into glycerol and free fatty acids (FFA).

The glycerol produced by LPL activity can be transported to the liver for various metabolic processes, including glycolysis, gluconeogenesis, and TAG synthesis.

Free fatty acids (FFA) released by LPL can be used for energy production in various tissues like skeletal muscle, heart, kidney, and liver. They can also be stored as TAGs in adipose tissue or transported to other tissues bound to albumin.