Lipid Digestion

Classes of Lipids

• Fatty Acids

• Triacylglycerides (TAG)

• Phospholipids

• Sphingolipids

• Free Sterols

• Sterol Esters

Functions of Lipids

• Structural Components of Cell Membranes

  • Provide integrity and fluidity to membranes.

• Energy Storage

  • Serve as an efficient energy reserve for the body.

• Provide Lubrication

  • Important in joints and for skin health.

• Signaling Molecules

  • Involved in cell signaling processes.

• Receptors

• Antigens

• Sensors

• Electrical Insulators

  • Essential for proper nerve function.

• Biological Detergents

  • Help in emulsifying fats in digestion.

• Membrane Anchors for Proteins

Fatty Acids Overview

Specific Fatty Acids

Lipid Composition in Adipose Tissue of Rats (µg/protein mg)

• Cholesterol: 43

• Total Phospholipids: 180

  • Phosphatidylcholine: 90

  • Phosphatidylethanolamine: 45

  • Phosphatidylserine: 16

  • Phosphatidylinositol: 10

  • Sphingomyelin: 5

  • Other phospholipid: 12

Lipid Digestion

• Dietary Lipids: Predominantly TAGs

• Average Intake: 33% of caloric intake

• Effectiveness of Digestion and Absorption: Very high, primarily occurs in the stomach and small intestine.

  • Mostly in the small intestine

Digestive Enzymes Involved in Lipid Digestion

• Gastric Lipase:

  • Hydrolyzes sn-3 ester bond.

    • Does better on medium chain FA compared to long chain FA

• Pancreatic Lipase:

  • Hydrolyzes sn-1 and sn-3 ester bonds; also acts on retinyl esters; requires colipase.

• Pancreatic Lipase-Related Protein 2:

  • Has a broad activity.

• Carboxyl Ester Lipase:

  • Exhibits broad activity.

• Pancreatic Phospholipase A2:

  • Hydrolyzes sn-2 of phospholipids.

• PLRP2 (Pancreatic Lipase-related protein 2)

  • acts as a versatile lipase, specifically essential for fat digestion in newborns, including milk fat globules

• Phospholipase B:

  • hydrolyzes the sn-1 and sn-2 positions of phospholipids, further contributing to the digestion and absorption of dietary fats.

• Sphingomyelinase:

  • catalyzes the breakdown of sphingomyelin into ceramide and phosphocholine, playing a crucial role in the metabolism of cell membranes and lipid signaling.

• Lactase-phlorizine hydroiase

  • catalyzes the hydrolysis of lactose into glucose and galactose, thereby facilitating the digestion of dairy products and providing essential energy sources.

• Ceramidase

  • catalyzes the hydrolysis of ceramide into sphingosine and free fatty acids, which is critical for maintaining cellular homeostasis and regulating various signaling pathways associated with cell growth and apoptosis.

Enterocytes

• Monoacylglycerol Pathway

• Glycerol 3-phosphate pathway

Lipids are either absorbed as MAG or free FA

Dietary Composition (g)

• Triacylglycerol: 70-100 g

• Phospholipids: 1-2 g

• Sphingolipids: 0.3-0.4 g

• Cholesterol: 200 g

• Cholesteryl Esters: 25-40 g

• Plasmalogens: 0.01-0.1 g

Digestive Process Overview

MOUTH

• Initial Digestive Action: Gastric lipase acts on dietary TAG and galactolipids (MGDG, DGDG) in the stomach.

SMALL INTESTINE - LUMEN

• Digestive Enzymes Activity:

  • Pancreatic lipase, PLRP2, and carboxyl ester lipase act on TAG to produce 1,2-DAG + FA

  • 1,2-DAG is further hydrolyzed to 2-MAG + FA and then to glycerol + FA

  • Phospholipase A2 hydrolyzes phospholipids to produce lysophospholipids + FA.

  • Sphingomyelin is converted to ceramide + phosphocholine.

  • Cholesteryl esters are converted to cholesterol + FA.

  • Retinyl esters are converted to retinol + FA.

  • MGDG and DGDG are hydrolyzed into monoglycerides and free fatty acids.

ENTEROCYTES - BRUSH-BORDER MEMBRANE

• Enzyme Activities:

  • Phospholipase B converts phospholipids to lysophospholipids + FA.

  • Sphingomyelinase breaks down sphingomyelin into ceramide + phosphocholine.

  • Lactase-phlorizine hydrolase acts on glycosylceramide and galactosylceramide.

Intracellular Lipid Metabolism

Pathways for Re-esterification

• Monoacylglycerol Pathway:

  • 2-MAG + 2 FA-COA → TAG + 2 COA

• Glycerol 3-Phosphate Pathway:

  • Glycerol 3-phosphate + 3 FA-COA → TAG + 3 CoA + P

• Lysophospholipid Pathway:

  • Lysophospholipid + FA-COA → Phospholipid - COA

• Cholesterol Esterification:

  • Cholesterol + FA-COA → Cholesteryl ester + COA

  • Involves ApoB-48, ApoA-IV, and ApoA-I in chylomicron synthesis.

Chylomicrons

• Synthesis Location:

  • Synthesized in the small intestine (SI)

• Components:

  • Contain apolipoprotein B-48, carry dietary lipids, large amounts of TAG along with cholesterol esters (CE) in the core, and non-esterified cholesterol and phospholipids on their surface.

• Transport Mechanism:

  • Absorbed into lacteals in the SI, carried through the lymphatic system to central circulation, and pick up other apolipoproteins while in circulation.

Portal Transport of Fatty Acids

• Small amounts of FA taken up into portal blood as NEFA (non-esterified fatty acid [free fatty acid {FFA}])

• MCFA and poly-unsaturated LCFA are more readily absorbed in portal blood

  • MCFA is most absorbed into portal blood

• NEFAs transported to liver this way can be re-esterified onto glycerol-3-P and packaged as VLDL

• Pathological conditions that impair CM synthesis enhance portal transport of NEFA

  • Chylothorax is a condition where lymphatic fluid accumulates in the pleural cavity, often leading to impaired lipid absorption and resulting in increased levels of chylomicrons in the bloodstream.

  • LCHAD Deficiency (Long chain 3-hydroxyacyl CoA dehydrogenase deficiency) is a rare genetic disorder that affects the body's ability to break down certain fats, leading to the accumulation of long-chain fatty acids and impairing lipid metabolism.

Orlistat

• Mechanism of Action:

  • Inhibits both gastric lipase and pancreatic lipase, leading to up to 30% reduction in digestion and absorption of lipids.

  • Fatty stool

    • A lot harder to control than normal stool

Absorption Process

• Hydrolysis by Brush Border Membrane Enzymes:

  • Dietary sphingolipids, phospholipids, and retinyl esters are hydrolyzed, allowing absorption into enterocytes.

  • Transport Mechanisms:

  • Absorption occurs via passive diffusion and carrier-mediated transport.

  • FABP - Fatty Acid Binding Protein - a cytoplasmic protein that binds fatty acids and facilitates their transport within enterocytes.

• Rapid Re-esterification:

  • Lipids are quickly re-esterified contributing to concentration gradient within the enterocytes.

• MPC1L1

  • Cholesterol transporter

    • 30-50%

  • Also plant sterols

    • ~5%

      • Plant sterols in your diet inhibit cholesterol absorption

  • MPC1L1 is targeted by medicine Ezetimibe

    • Lowers absorption for dietary cholesterol

Example Product for Special Needs

Pregestimil®

• Target Group:

  • Infants with fat absorption issues or sensitivity to intact proteins.

• Composition:

  • Contains 55% fat from MCT oil, hypoallergenic, lactose-free, and enriched with DHA and ARA for brain and eye development.

Enfaport™

• Target Group:

  • Designed for infants with Chylothorax or LCHAD deficiency.

• Composition:

  • High levels of MCT oil for better fat absorption, high protein content, includes essential fatty acids, DHA, and ARA.