top of page

Lipids: Structure, Digestion & Absorption

image.png

Lipids

Lipids are...

  • biomolecules that contain fatty acids or a steroid nucleus

  • soluble in organic solvents but not water

  • extracted from cells using organic solvents

Types of lipids: 

  • waxes

  • fats and oils

  • phospholipids

  • prostaglandins

image.png

Fatty Acids

Fatty acids are 

  • long chain carboxylic acids

  • usually 12-18 carbons

  • insoluble in water

  • saturated or unsaturated 

Fatty acid formulas

  • condensed formula

  • line bond formulas

image.png
image.png

Properties of saturated fatty acids

  • only contain single bonds

  • are closely packed

  • have high melting points

  • solids at room temp

image.png

Properties of unsaturated fatty acids

  • contain one (MUFA) or multiple (PUFA) cis double C=C bonds

  • have "kinks" in the fatty acid chains

  • low melting points

  • liquids at room temp

image.png
image.png

Naming Fatty Acids

image.png

Nomenclature

image.png

Omega-6 and Omega-3 Fatty Acids

  • vegetable oils are mostly omega-6 with the 1st C=C at C6 from the omega end

  • fish oils are mostly omega-3 with the first C=C at C3 from the omega end

image.png

Essential Fatty Acids

Essential fatty acids are fatty acids that we MUST obtain from the diet - our bodies cannot synthesize them

  • PUFA linoleic (18:2 n-6) and linolenic acids (18:3 n-3)

  • humans lack the enzyme to insert double bond beyond omega-9 carbon

  • plant foods such as peanuts, corn, and safflower

  • precursors for

    • prostaglandins

    • leukotrienes

    • thromboxanes

  • important in maintaining membranes and lowering plasma and cholesterol levels

image.png

  • n-3 and n-6 compete with each other

    • same enzymes for elongation and desaturation

    • why the n-3/n-6 ratio is important

  • functional molecules derived from n-3 and n-6 often function in different ways

Prostaglandins

  • 20 carbon atoms in their fatty acid chains

  • an -OH on C11 and C15

  • a trans double bond at C13

  • formed from omega-6 FA and omega-3 FA

prostaglandins are: 

  • produced by injured tissues

  • involved in pain, fever and inflammation

  • not produced when anti-inflammatory drugs such as aspirin inhibit their synthesis 

image.png

Triaglycerols (TAGs)

Triglyceride

  • Fats and oils are also called triaglycerols

  • esters of glycerol

  • produced by esterfication

  • formed when the hydroxyl groups of glycerol react with the carboxyl groups of FAs

image.png
image.png

Oils

  • have more unsaturated fats

  • have cis double bonds that cause "kinks" in the fatty acid chains

  • with "kinks" the TAG molecules in the chain cannot pack close together

  • unsaturated TAG -->

image.png

Cis vs Trans bonds

image.png

Hydrogenation and Trans Fatty Acids

  • Most naturally occuring fatty acids have cis double bonds

    • during hydrogenation, some cis bonds are converted to trans bonds​

    • trans fatty acids behave like saturated fatty acids

    • 2-4% of our calories are in the form of trans fatty acid

    • trans fatty acids raise LDL and lower HDL cholesterol

Phospholipids

  • hydrophilic polar head (PO4 end)

  • long hydrophobic hydrocarbon tail

  • major components of membranes

  • amphipathic

  • most in membranes are phosphoglycerides (glycerol as the backbone)

    • fatty acids at carbons 1 and 2​

    • phosphoric acid attached at carbon 3

image.png

  • If attached to an alcohol by an ester linkage to the phosphate group, you get other phosphoglycerides

    • phosphatidylcholine​ (lecithin) 

    • phosphatidylethanolamin (cephalin) 

    • phosphatidylserine

    • lecithin and cephalin most prominent in membranes

image.png

Lipid Digestion

Dietary lipids

  • triaglycerols (TAGs)

  • phospholipids

  • sterols (mainly cholesterol)

Enzymes

  • lipases

  • phospholipases

  • cholesteryl esterase

Bile acids and bile salts as emulsifiers

image.png

Helpful Visuals

image.png
image.png
image.png

Digestion of Lipids

In the mouth (lingual lipase) and the stomach (gastric lipase)

Gastric Lipase

  • hydrolyze fat at sn-3 carbon (carbon 3)

  • TAGs with medium chained FAs  are hydrolyzed quicker than TAGs with long chained FAs

  • does NOT hydrolyze cholesterol esters or phospholipids

  • the natural movements of the stomach help disperse the lipid into droplets that move into duodenum 

Issues in the small intestine

  • lumen is an H2O environment (fats are hydrophobic)

  • mucosal cell

    • brush border is a lipid environment (good)

    • cell interior is an H2O environment

    • blood is an H2O environment

    • therefore will need transporters and emulsifiers (chylomicrons, bile)

Lipid emulsion enters small GI

  • continues hydrolysis

  • solubilization of products in lumen

  • diffusion across water in lumen to brush border membrane

BILE SALTS

  • biological determinants

  • help make emulsions

  • micelles (aggregates of bile salts)

  • mixed micelles (bile salts and other lipids)

EMULSIONS

  • process that breaks down large triglycerides and bile acids

  • allows pancreatic lipase and cholesterol esterase

    • breaks up fat droplets, therefore increasing surface area for enzyme action​

image.png

Colipase is a heat stable protein from the pancreas. It helps pancreatic lipase bind to TAG at a 1:1 ratio

Pancreatic lipase with colipase

Digestion also occurs in small intestine!

1. Hydrolysis​​

  • mostly pancreatic lipase with the help of bile salts

  • also cholesterol esterase secreted by pancreas as active enzyme

  • self-aggregation to protect itself from proteolytic inactivation

  • also hydrolyzes all 3 ester linkages in TAG

  • there is also phospholipase A2​

    • from pancreas​

    • activated in the lumen

    • attacks sn-2 ester linkage (lysophospholipids)

  • lysophospholipids can also work as emulsifiers because they are amphipathic

  • some phospholipids secreted as part of bile to aid in digestion

image.png
image.png
image.png
image.png

2. Solubilization

  • bile salts + products form a MICELLE, or mixed micelle

  • products: 

    • 2-monoacylglycerol​

    • FFAs

    • cholesterol

    • lysophospholipids

  • micelles are what are need to diffuse across the unstirred water layer

image.png

3. Diffusion

the "unstirred water layer"

  • the epithelial surface of the small GI is surrounded by a layer of water = unstirred water layer​

  • the thickness of this layer depends on how vigorously contents are mixed

  • increased mixing reduces the thickness of this layer

  • this layer is a barrier that the products of lipid digestion must cross before they can be absorbed by enterocytes

HOW EXACTLY DO MICELLES WORK?

  • allows digestion products to mix

  • makes them soluble in the water phase in the lumen since they can readily cross the unstirred water layer

  • increases concentration of lipid products favoring diffusion across the brush border membrane

image.png

Overview of Lipid Digestion

image.png
image.png

Lipid Absorption

FOUR STEPS

  1. diffusion of digestion products across brush border membrane

  2. reesterfication​​ (MAG + FA --> TAG, Chol + FA --> CE)

  3. synthesis of chylomicrons

  4. release of chylomicrons from the cell to lymphatic system

1. absorption across brush border

  • mostly in jejunum

  • firstly, the micelle breaks apart

  • the components diffuse down gradient across lipid membrane into cell

  • bile stays in lumen until it reaches ileum

    • reabsorbed into the liver via enterohepatic circulation​

Inside mucosal cells

  • short and medium chain fatty acids

    • <10-12C​

    • water miscible

    • leave mucosal cell to go to liver via portal vein

      • similar to AAs and glucose​

      • stay free as FAs

      • bind to albumin in blood

2. Reesterfication inside mucosal cells

  • other lipid products than short and medium chain FAs

  • need to be reesterfied before released from muscosal cell

  • resynthesized via ester linkages

    • 2-monoglyceride + 2 FA --> TAG​

    • Chol + FA --> CE

    • lysophospholipids + FA --> PL

  • still not water soluble

Inside mucosal cell

  • reesterfication also helps keep intracellular concentration of lipid products low to help aid absorption of products into the cell

    • maintains a low concentration relative to the lumen​

    • favors cellular uptake

3. chlyomicron synthesis

  • need to get lipid reesterfied products ready for release in blood

  • to make this happen, they get wrapped up in a lipoprotein called chlymicron

    • only carries exogenous dietary lipids​

  • chylomicrons are VLDLs because it has a high amount of lipids compared to protein

    • lipids are less dense than proteins​

  • contains TAG, PL, CE, and retinyl esters (vitamin A)

image.png
image.png

4. release of chylomicrons

  • chylomicrons are released by exocytosis into the lymphatic system

image.png

©2023 by Syracuse University Dr.Margaret Voss

bottom of page