Download Lecture 15

Digestion and absorption of
dietary fats in non-ruminants
Background and Review
• Fatty acid nomenclature relevant to this
advanced nutrition class
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14:0 myristic acid
16:0 palmitic acid
18:0 stearic acid
18:1 cis Δ 9 oleic acid
18:2 cis Δ 9,12 linoleic acid
18:3 cis Δ 9,12,15 linolenic acid
20:4 cis Δ 5,8,11,14 arachidonic acid
20:5 cis Δ 5,8,11,14,17 eicosapentaenoic acid (an
omega-3 fatty acid because of double bond 3 C from
distal end)
Nomenclature
• Chain length
– Medium chain: caproic (C6), caprylic (C8),
capric (C10) and lauric acid (C12)
– Long chain: C14……..
• Saturation
– Saturated (C16:0)
– Monounsaturated (C18:1)
– Polyunsaturated (C20:4)
Nomenclature
•
Position of first double bond relative to carboxylic acid or methyl end
– n−3 fatty acids: referred to as n-3 (ω−3 fatty acids or omega-3 fatty acids); a
family of unsaturated fatty acids that have a double bond in the “n-3” position;
that is, the third carbon from the methyl end of the fatty acid
C20:5, n-3 (eicosapentaenoic acid)
From the acid end, Δ 5,8,11,14,17
Nomenclature
•
Position of first double bond relative to carboxylic acid or methyl end
– n−6 fatty acids: referred to as n-6 (ω−6 fatty acids or omega-6 fatty acids); a
family of unsaturated fatty acids that have a double bond in the “n-6” position;
that is, the sixth carbon from the methyl end of the fatty acid
C18:2, n-6 (linoleic acid)
If discuss with respect to the acid end, we would use: 18:2 cis Δ 9,12
Lipid Digestion-The Overview
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Digestion to component parts
Absorption of component parts by enterocytes
Reassembly of complex lipids
Delivery to systemic circulation via blood (or
lymphatics)
• Uptake by recipient peripheral tissues (liver,
adipose tissue, muscle)
• Metabolism and utilization for energy or other
processes
Fundamental Problem
• Fatty acids are not stored in feeds or
animal tissues as fatty acids, they are
stored as triglycerides (triacylglycerol
esters), phospholipids, etc.
– Complexed lipids must be digested and the
constituent parts absorbed by the enterocyte
Triacylglycerol ester
Solution to problem
• Must hydrolyze to component parts before
molecules can traverse the lumen of the
intestine and be absorbed by the
enterocyte
• Must be able to accommodate
hydrophobic molecules in an
aqueous/hydrophilic environment
Digestion
• Lipases
Triacylglycerol (TAG) digestion
• Gastric/Lingual Lipase (Acid Lipase)
• Sn-3 position→ 1,2 DAG + FA to help emulsify additional
fat
• Active to pH 6.5 (through upper duodenum)
• Prefers triglycerides composed of medium chain FA
(milks are rich in MCT)
• Particularly important for newborns and suckling young
due to slow development of pancreatic lipase
• No activity on PL or cholesterol esters
• Gastric lipase + mixing/motility → fine lipid droplets less
than 0.5 mm diameter
Most fat digestion occurs in the
small intestine
• Pancreatic lipase
• Sn-1 and 3 positions → FFA + 2-MAG
• Requires co-lipase to function in presence
of bile salts:
pro-colipase + trypsin → co-lipase
co-lipase + lipase → TAG hydrolysis
Not all fatty acids are equally
absorbed by the enterocyte
• Lard: saturated fatty acids esterified in the
sn-2 position: lipase activity produces 2MAG + free fatty acids, many of which are
unsaturated
– As the free fatty acid, unsaturated fatty acids
are more readily absorbed than are saturated
fatty acids
Not all fatty acids are equally
absorbed by the enterocyte
• Beef Tallow: saturated fatty acids
esterified in the sn-1 and sn-3 positions:
lipase activity produces 2-MAG + free fatty
acids, many of which are saturated
– As the free fatty acid, saturated fatty acids are
less readily absorbed than are unsaturated
fatty acids
Which has the higher metabolizable energy value,
lard or beef tallow?
• Lard: less energy lost due to lack of
absorption, BECAUSE saturated fatty
acids are more readily absorbed as the 2MAG, and because unsaturated fatty acids
are more readily absorbed than saturated
fatty acids
Animals not consuming just TAG
• Phospholipids
Phospholipid digestion
•Phospholipase A2
- secreted by pancreas, some activity
intrinsic in intestinal mucosa depending on
species
- activated by trypsin
- targets sn-2 postion (FFA + Lysophosphatidyl choline)
Digestion of Cholesteryl Esters
The R (fatty acid group) varies across plants and across animals
Digestion of Cholesteryl Esters
• Cholesterol esterase (carboxyl ester hydrolase,
bile salt-stimulated lipase, nonspecific esterase)
– Secreted by pancreas, no activation required
– Broad esterase activity (TAG, CE,
phosphoglycerides, spingolipids, A, D, MAG)
– Bile salt micelles (sodium taurocholate); self
aggregation to polymeric form (dimer) to
protect against proteolytic degradation
How do we get lipid digestion products into the blood for
distribution to recipient tissues?
• Lipids have little solubility in water
(minimal polarity)
• “Unstirred water layer”, presents a barrier
even with vigorous intestinal motility and
mixing of intestinal contents
Bile is crucial for absorption of
lipids
• Bile is produced by hepatocytes in the liver, and drains out through
the many bile ducts that penetrate the liver
• The common bile duct in turn joins with the pancreatic duct to empty
into the duodenum; If the sphincter of Oddi is closed, bile is
prevented from draining into the intestine and instead flows into the
gall bladder, where it is stored and concentrated
• Cholesterol is released with the bile, dissolved in the acids and fats
found in the concentrated bile solution
• When food is released by the stomach into the duodenum in the
form of chyme, the gallbladder releases the concentrated bile to
provide bile salts to aid in digestion
Mixed Micelles at CMC (1-2 mM)
• Micelles form from bile salts (acids) + lipid
moieties (cholesterol, etc.), engulf hydrophobic
products of fat digestion, and provide the
polarity that enables these molecules to
penetrate the unstirred water barrier
• Increase the concentration of lipid digestion
products (100-1000X)
• Diffusion is thus toward the enterocyte
Micelles
Entering the Enterocyte
• Passive
– Lipid-rich brush border
Initial diffusion
followed by
re-esterification at
the endoplasmic
reticulum
– TAG, phospholipids, cholesterol esters reformed to
sustain [gradient]
– Glycerol, short chain FA, readily diffuse through
unstirred water barrier and into enterocyte due to
[gradient]
Carrier-mediated active transport
Fatty acids
FATP-4
• High concentrations of FA in the lumen:
diffusion is likely major mechanism of
uptake
Fatty acids
• Importance of FATP-4 increases as the
concentration of FA decreases
Intracellular Metabolism
• Must traverse an aqueous cytosol to get to
ER
– FABP (Villi vs. crypt; jejunum vs. ileum; high
fat diet vs. low fat diet)
– I-FABP (fatty acids only)
– L-FABP (lysophosphatidyl choline,
retinoids,…, MAG)
– SCP-1
– SCP-2 (cholesterol)
Re-esterification
• Triacylglycerol complex on cytosolic
surface of the ER
– Then TAG must penetrate the ER; aided by a
transport protein
– Abetalioproteinemia- chylomicrons not
formed, despite presence of apoB
Phospholipids
– Lysophatidyl choline, etc.
Acylated
Phosphatidyl choline
Hydrolyzed
glycerol 3-phosporyl choline
+
liver
fatty acids
MAG
TAG
– 2 lysophatidyl choline
phosphatidyl choline
+
Glycerol 3-phosporyl choline
Cholesterol
Cholesterol (diet and endogenous)
Free
Pool
•chylomicrons
LYMPH
Chylomicrons
• Apo A-1, apo A-II, apo B-48
apoE and C added in circulation
• Fatty acid composition ~ diet
(unlike phospholipids)
• ER Golgi prechylomicrons
Exocytosis
intracellular space
Avian vs. Mammalian Species
• Mammals: chylomicrons, enter circulation
via the lymphatics at the thoracic duct
• Avian: portomicrons, transported to the
liver via the portal vein, then delivered to
systemic circulation
Summary
• Digestion: lipases
• Micelle formation
• Uptake of component parts by diffusion and carrier
mediated (FATP) processes
• Reassembly of triglyceride via MAG or glycerol phosphate
pathways
• Incorporation of TAG, etc. and apo proteins into
lipoproteins called chylomicrons (or portomicrons) in
enterocyte
• Secretion via exocytosis and entry in systemic circulation
via lymphatics or portal circulation via liver