Lipids are water-insoluble organic molecules that can be extracted from tissues by nonpolar solvents.
They are present as membrane-associated components, lipoproteins, or droplets of triglycerides in adipose tissues.
Lipids are a major source of energy.
They play a role in dissolving fat-soluble vitamins, which have regulatory or coenzyme functions in the body.
Prostaglandins and steroid hormones are involved in the body’s homeostasis.
Lipid Digestion
An adult typically ingests 60-90 g of fat per day, with 90% as triglycerides and the rest as cholesterol, phospholipids, and free fatty acids.
Digestion starts in the stomach via lingual lipase and gastric lipase.
These enzymes primarily target triglycerides with short and medium chain length fatty acids (less than 12 carbons).
These enzymes are important in neonates for digesting fat in milk and in people with cystic fibrosis (who lack pancreatic lipase).
Emulsification of dietary lipids occurs in the duodenum with the aid of bile salts and peristalsis, which increases the surface area for digestion.
Bile salts are produced in the liver and stored in the gallbladder.
Triacylglycerol Degradation
Triacylglycerols are degraded by pancreatic lipase into 2-monoacylglycerol and free fatty acids.
Colipase, activated by trypsin, binds to lipase in a 1:1 ratio and anchors it to the lipid-aqueous interface.
Orlistat, an anti-obesity drug, inhibits gastric and pancreatic lipase, thereby decreasing fat absorption.
Cholesteryl Ester Degradation
10-15% of cholesterol is present in esterified form.
It is hydrolyzed by pancreatic cholesterol esterase to cholesterol and free fatty acids.
The activity of cholesterol esterase is increased in the presence of bile salts.
Cholesterol esterase breaks down fatty acids attached to the OH group, converting the compound from mostly nonpolar to polar (due to the remaining OH). This process is called hydrolysis, yielding Cholesterol + Free Fatty acids
Phospholipid Degradation
Phospholipids, like phosphatidylcholine, are degraded by phospholipase A2 in the presence of bile salts, which removes a fatty acid from C2 of the phospholipid to form lysophospholipid.
Lysophospholipid is then hydrolyzed by lysophospholipase, which releases a free fatty acid and a glyceryl phosphoryl base.
Glyceryl phosphoryl base can be excreted in feces, further degraded, or absorbed.
Control of Lipid Digestion
Lipid digestion is hormonally controlled.
Cholecystokinin (CCK)
Secreted from the mucosa of the jejunum and lower duodenum.
Stimulates the gallbladder to release bile.
Stimulates the pancreas to release pancreatic enzymes.
Secreted by intestinal cells in response to lower pH of the chyme.
Causes the pancreas and liver to release bicarbonate, which neutralizes the pH to the optimum level for pancreatic enzymes to function.
Optimum pH of pancreatic enzymes: 6-7 (same pH in the intestine).
Absorption of Lipids by Intestinal Mucosal Cells
The degradation products of lipids, along with bile salts, form mixed micelles (hydrophobic inside and hydrophilic outside).
The hydrophilic surface facilitates the transport of hydrophobic lipids through the unstirred water layer to the brush border membrane, where they are absorbed.
Formation of mixed micelles is not required for the absorption of short and medium chain length fatty acids.
The mixed micelles have a polar exterior and a hydrophobic interior. Cholesterol has an OH group on the outside.
The unstirred water layer requires compounds to be polar in order to pass through
Short and medium chain fatty acids do not require mixed micelles for digestion by lingual and gastric lipase and absorption
Lipid Re-synthesis in Enterocytes
In enterocytes, triacylglycerols and cholesteryl esters are resynthesized.
Short and medium chain length fatty acids are not converted to their CoA derivatives but are released into portal circulation and carried by serum albumin to the liver for metabolism.
Monoacylglycerol and fatty acids combine to form triglycerides, which associate with lipoproteins and enter the circulation.
Lipid Malabsorption (Steatorrhea)
Cystic fibrosis
Shortened bowl
Both cause a decrease in the absorption of lipids (including fat-soluble vitamins and essential fatty acids), leading to an increase in lipids in feces (Steatorrhea).
The pancreatic duct becomes blocked, impairing the secretion of pancreatic enzymes, which leads to digestion problems.
Gallbladder issues can also decrease bile salt secretion which are needed for emulsification and enzyme activation.
Shortened bowels reduce surface area, impeding on fat absorption.
Secretion of Lipids from Enterocytes
Phospholipids, unesterified cholesterol, and apolipoprotein B-48 are located at the outer layer.
Triacylglycerols and cholesterol esters form the core of chylomicrons, which are released to the chyle (giving it a milky appearance).
This chyle is then released into the blood.
Activation occurs via the addition of CO-A to fatty acids by fatty acid CO-A with Acyltransferase, while 2 Monoacylglycerol combines with fatty acids using Monoacylglycerol-acyltransferase which produces triglycerol using Diacylglycerol- Acytltransferase
Use of Lipids in Tissues
Triacylglycerol is broken down primarily in the capillaries of skeletal muscle, adipose tissues, heart, lung, kidney, and liver.
Triacylglycerol in chylomicrons is degraded to free fatty acids and glycerol by lipoprotein lipase. This enzyme is synthesized primarily by adipocytes and muscle cells.
Familial lipoprotein lipase deficiency (type I hyperlipoproteinemia) is a rare, autosomal recessive disorder resulting from a deficiency of lipoprotein lipase or its coenzyme, apo C-II. The result is massive chylomicronemia.
Fate of Free Fatty Acids
The free fatty acids derived from the hydrolysis of triacylglycerol may directly enter adjacent muscle cells or adipocytes.
They may be transported in the blood in association with serum albumin until they are taken up by cells.
Most cells can oxidize fatty acids to produce energy.
Adipocytes can also re-esterify free fatty acids to produce triacylglycerol molecules, which are stored until the fatty acids are needed by the body.
Fate of Glycerol
Glycerol released from triacylglycerol is almost exclusively used by the liver to produce glycerol 3-phosphate, which can enter either glycolysis or gluconeogenesis by oxidation to dihydroxyacetone phosphate.