[PHARM 113] Lipids Part 1

Prof. Robertson G. Rivera I BS Pharmaceutical Sciences Batch 2018

DIGESTION AND TRANSPORT OF DIETARY LIPIDS

I. Digestion of Triacylglycerols
A. Action of Bile salts
Triacylglycerols (TAGs):
~major source of dat in the human
diet because they are the major
storage lipid in plants and animals
~conrains glycerol backbone to
which 3 fatty acids are esterified stomach
Dietary fat
Main route for digestion of TAGs
involve hydrolysis to fatty acids &
2-monoacyglycerols Emulsified by bile salts

Illustration: Bile salts:

> they emulsify fat to make it easier for
TAGs pancreatic lipases to digest
> amphipathic compounds
hydrolysis
> synthesized in the liver
Fatty acids +
> secreted via gall bladder to intestinal
2-monoacylgylcerols
lumen
Lumen ng intestine Cholecystokinin:
> a gut hormone that stimulates the
**route depends on the chain contraction of the gall bladder + secretion
length of the fatty acids of pancreatic enzymes
> is secreted by the intestinal cells when
Lingual and gastric lipases: stomach contents enter the small intestine

~Produced by cells at the back of the

tongue and in the stomach
~hydrolyze short and medium chain
fatty acids (C4 to C12) from dietary
triacylgylcerols
~Most active in infants and young
children (usually yung lactose
intolerance nagmamanifest lang as an
adult pag di ka na umiinom ng gamot)
 [PHARM 113] Lipids Part 1
Prof. Robertson G. Rivera I BS Pharmaceutical Sciences Batch 2018
B. Action of Pancreatic Lipase
Pancreatic lipase:
>major enzyme that digests dietary
triacylglycerols
>hydrolyzes fatty acids of all chain
lengths (basta nasa position 1 and 3 of
the glycerol moiety ng triacylglycerol,
ika-cut niya)
>is secreted with colipase
*colipase binds to the dietary fat and to
the lipase, which then increases
*bicarbonate raises pH to 6
*bicarbonate secretion from pancreas is
stimulated by the hormone secretin
*secretin is released from the intestines
when acid enters duodenum
Accdg sa book, bile salts increase lipase
activity (they make it easier for the enzyme
to break down triacylglycerols) by breaking
down TAGs into micelles. Pinapalibutan
niya yung small groups ng TAG para di sila
magclump together; so parang nagiging
membrane yung bile salts.
This set-up exposes more TAGs to be
broken down by lipase. (more surface
area, faster reaction)
However, too much of bile salts, can also
cause inhibition. Pag lumampas siya sa
tamang concentration (called critical
micelle concentration), magiging inihibitory
na yung effect niya. At this, point, it
surrounds the TAGs so much so that the
lipase can’t get to it na.
This is where colipase comes in. Colipase
allows the TAGs to enter the active site of
the enzyme. ( in the previous discussion it
was mentioned that colipase binds to both
TAG and lipase, thus increasing enzymatic
activity
Example: fats in milk
The mammary gland produces milk.
*milk:
> is a major source of nutrients for
a breastfed human infant
>fatty acid composition varies
depending on the mother’s diet
but long-chain fatty acids
predominate
> sa cows milk, there’s more short
and medium chain fatty acids w/
no long chain.
Concentrations of pancreatic lipase and
bile salts are low in the intestinal lumen of
infants.
But fat from human milk is still readily
absorbed.
Lingual and gastric lipases produced by
the infant partially compensate for the
lower levels of pancreatoc lipase.
Besides that, mamary glands also
produces lipases that enter milk.
(translation/ explanation on next page)
 [PHARM 113] Lipids Part 1

Prof. Robertson G. Rivera I BS Pharmaceutical Sciences Batch 2018

translation/ explanation for milk example Hemolytic anemia

-> yung fatty acid composition ng gatas ay

Nasisira yung RBCs
iba-iba depende sa kinakain ng nanay
pero kadalasan, marami itong laman na
long-chain fatty acids. Hemoglobin is released
-> halos pareho lang ang laman ng human
at cow milk, except yung cow milk ay
puno ng short and medium chain fatty Hemoglobin is further d degraded into
acids (C4 -C12) unlike yung human heme and protein

milk na puro long-chain

-> tapos, sa baby, konti lang yung
pancreatic lipase and bile salt niya.
Kaya parin niya magdigest at
mag-absorb ng human milk sa tulpong
ng lingual at gastric lipases produced
by the infant. Dagdag pa rito, meron din
napo-produce na lipase yung mammary
gland.
Diseases associated with bile excess:
1. Hemolytic anemia
> condition in which red blood cells are
destroyed faster than they are created so
you end up with a less than normal
amount of blood.
Good explanation:
youtube.com/watch?v=ZrnWYmJ0SZA
Time stamps: 3:27 and 9:40
*hemolytic anemia causes an increase in
concentration of bilirubin
Bilirubin:
~ degraded form of the heme of
hemoglobin
~ contributes to the increase of
production of bile salts
Heme is further degraded to bilirubin and
iron
Bilirubin enters the liver
Karamihan sa bilirubin na pumapasok sa
liver is in less water-soluble form (isipin
mo nalang medj insoluble)
Magprecipitate siya sa gall bladder at gall
stones
Kung maliit naman, pweds na daw itae.
2. Steatorrhea
> Fat laden stools caused by
malabsorption of of dietary fats
> caused by a lack of pancreatic
secretion (pancreatic lipase)
> di mo nada-digest yung fat kaya
tinatae mo nalang. Kaya oily yung tae mo.
Diseases associated with pancreatic
lipase:
> elevated serum levels of pancreatic
lipase and pancreatic amylase
~causes acute or chronic panreatitis
~due to escape of enxzymes from
inflamed exocrine cells of pancrease
 [PHARM 113] Lipids Part 1
Prof. Robertson G. Rivera I BS Pharmaceutical Sciences Batch 2018
II. Absorption of Dietary Lipids
fatty acids + 2-monoacylglycerols are
emulsified by bile salts
micelles travel through a layer of water
arrive at the microvilli on the surface of
the intestinal epithelial cells
absorption of everything except bile salts
bile salts travel to the ileum
ileu resorbs 95% of bile salts but gets rid
of 5%
resorbed bile salts travel throgh the
enterohepatic circulation
reaches the liver
goes into the bile for storage (parang
stored as bile instead of bile salts?)
goes to the gall bladder for storage
ejected to the intestinal lumen during
digestion (cycle restarts)
**short and medium chain fatty acids do
not require bile salts for their absorption.
They enter portal blood vessels then the
lymph where they are bound to albumin.
III. Synthesis of Chylomicrons
*u can think of chylomicrons as the
transportable form of TAGs
In the epithelial cells, fatty acids and
2-monoacylglycerols undergo
condensation via enzymatic reactions in
the smooth ER to reform into
triacylglycerols.
The process is discussed in detail below:
Fatty acids are activated by turning into
fatty acyl CoA
Fatty acyl CoA reacts with
2-monoacylglycerol to form diaglycerol
Diaglycerol reacts with another fatty acy
CoA to form a triacylglycerol
Triacylglycerols are repackaged by
intestinal cells together with proteins and
phospholipids in the chylomicrons,
otherwise magka-clump yung TAG sa
blood
**This process differs when it occurs
in the liver and adipose cells.
~in intestines, the intermediate is
2-monoacylglycerol
~for others, it’s phosphatidic acid
 [PHARM 113] Lipids Part 1

Prof. Robertson G. Rivera I BS Pharmaceutical Sciences Batch 2018

B-48: LPL:
> major apoprotein associated with ~enyme in capillary endothelial cells sa
chylomicrons as they leave intestinal muscle and adipose tissue, na
cells. nagda-digest ng TAG sa chylomicrons at
> structurally and genetically related to VLDL in the blood.
B-100 apoprotein
V. Fate of Chylomicrons
IV. Transport of Dietary Lipids in the
Blood TAGs are digested by LPLs. LPLs are
attached to proteoglycans in the basement
● The whole process is called membranes of endothelial cells that line
“exocytosis” the capillary walls.

Chylomicrons are secreted by intestinal LPLs are produced in:

epithelial cells >adipose cells - has higher Km than
isozyme in muscle cells
They are secreted into the chyle of the >muscle cells
lymphatic system
>lactating mammary glands
Enter the blood through the thoracic duct
at this point they are called ‘nascent’ or *Insulin:
newborn chylomicrons ~stimulates the synthesis and secretion
They accept proteins from HDL within the of adipose LPL
lymph and the blood ~facilitates hydrolysis of fatty acids from
TAGs
After that they mature and are called
mature chylomicrons
*fatty acids
~ are not very solubke in water so tehy
The proteins transferred to nascent
have to be complexed with albumin in
chlyomicrons from HDL are:
order to avoid precipitating in your blood
vessels
1. Apoprotein E (apoE)
~ it is mainly stored as triacylglycerols in
~recognized by membrane receptors
adipose tissue
in the surface of liver cells.
~ can also be oxidized for energy in
~allows apoE-bearing lipoproteins to
muscle and other tissues
enter liver cells by endocytosis
~digested by lysosomes

2. Apo CII
~activates LPL
 [PHARM 113] Lipids Part 1

Prof. Robertson G. Rivera I BS Pharmaceutical Sciences Batch 2018

Significance nung Km for LPL produced

in adipose cells:

High conc of fatty acids will activate LPL in

adipose tissue and turn fatty acids to fats.
The ones in the muscle cells have lower
Km which means they can extract fatty
acids from the blood to be used for energy
even at low concentrations.

Glycerol released from chylomicron TAGs

by the LPL may be used for TAG synthesis
in the liver during the fed state

Chylomicron left in the blood is called

chylomicron remnant

These remnants still bind to receptors or

hepatocytes which recognise apoE and is
taken up by the process of endocytosis

Lysosomes and endocytic vesicles merge

to form a pocket/container containing
lysosomal enzymes

Chlylomicron remnants go to this merged

container

Remnants are finally degraded by

lysosomal enzymes