Digestion and absorption of dietary fats in non-ruminants

1

• Digestion and absorption of dietary fats in
  non-ruminants

2
Background and Review

• Fatty acid nomenclature relevant to this advanced
  nutrition class
• 140 myristic acid
• 160 palmitic acid
• 180 stearic acid
• 181 cis ? 9 oleic acid
• 182 cis ? 9,12 linoleic acid
• 183 cis ? 9,12,15 linolenic acid
• 204 cis ? 5,8,11,14 arachidonic acid
• 205 cis ? 5,8,11,14,17 eicosapentaenoic acid (an
  omega-3 fatty acid because of double bond 3 C
  from distal end)

3
Nomenclature

• Chain length
• Medium chain caproic (C6), caprylic (C8), capric
  (C10) and lauric acid (C12)
• Long chain C14..

• Saturation
• Saturated (C160)
• Monounsaturated (C181)
• Polyunsaturated (C204)

4
Nomenclature

• Position of first double bond relative to
  carboxylic acid or methyl end
• n-3 fatty acids referred to as n-3 (?-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

C205, n-3 (eicosapentaenoic acid)
From the acid end, ? 5,8,11,14,17
5
Nomenclature

• Position of first double bond relative to
  carboxylic acid or methyl end
• n-6 fatty acids referred to as n-6 (?-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

C182, n-6 (linoleic acid)
If discuss with respect to the acid end, we would
use 182 cis ? 9,12
6
Lipid Digestion-The Overview

• 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

7
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

8
Triacylglycerol ester
9
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

10
Digestion

• Lipases

11
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

12
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

13
Not all fatty acids are equally absorbed by the
enterocyte

• Lard saturated fatty acids esterified in the
  sn-2 position lipase activity produces 2-MAG
  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

14
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

15
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 2-MAG, and because unsaturated
  fatty acids are more readily absorbed than
  saturated fatty acids

16
Animals not consuming just TAG

• Phospholipids

17
Phospholipid digestion

• Phospholipase A2
• - secreted by pancreas, some activity intrinsic
  in intestinal mucosa depending on species
• - activated by trypsin
• - targets sn-2 postion (FFA
  Lyso- phosphatidyl choline)

18
Digestion of Cholesteryl Esters
The R (fatty acid group) varies across plants and
across animals
19
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

20
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

21
(No Transcript)
22
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

23
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
24
Micelles
25
Entering the Enterocyte

• Passive
• Lipid-rich brush border
• TAG, phospholipids, cholesterol esters reformed
  to sustain gradient
• Glycerol, short chain FA, readily diffuse through
  unstirred water barrier and into enterocyte due
  to gradient

Initial diffusion followed by
re-esterification at the endoplasmic reticulum
26
Carrier-mediated active transport
Fatty acids

• High concentrations of FA in the lumen
• diffusion is likely major mechanism of
• uptake
• Importance of FATP-4 increases as the
• concentration of FA decreases

FATP-4
Fatty acids
27
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)

28
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

29
(No Transcript)
30
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

31
Cholesterol
Cholesterol (diet and endogenous)
Free Pool

• chylomicrons

LYMPH
32
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

33
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

34
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