218
chapter 12
Gastrointestinal Digestion and Absorption
vein. Thus, medium-chain triacylglycerols can be digested
and absorbed in the presence of minimal amounts of pan-
creatic lipase and in the absence of bile salts. For this
reason, they are used to supplement energy intake in pa-
tients with malabsorption syndromes. Coconut oil is rich
in trioctanoyl-glycerol (
8
-carbon) and tridecanoylglycerol
(
1 0
-carbon).
In tra c e llu la r (M u co sa l) P h a se
Fatty acids (long-chain) are activated and monoacyl-
glycerols are converted to triacylglycerols at the smooth
endoplasmic reticulum. The steps involved are as follows:
1. Conversion of fatty acids to acyl CoA derivatives by
acyl-CoA synthetase.
RCOCT + HSCoA + ATP4“
^
RCOSCoA + AMP
2
+ PP2“
2. Esterification of monoacylglycerol to diacylglycérol
and triacylglycerol catalyzed by monoacylglycerol
transacylase and diacylglycérol transacylase,
respectively.
H 2C O H
h
2
C O O C R ,
I
I
R jC O O C H
+ R C O S C o A
î î R 2C O O C H
+ C o ASH
I
I
H 2C O H
A cyl-C oA
H 2C O H
M o n o ac y lg ly c e ro l
D iacy lg ly céro l
h
2
c o o c r ,
h
2
c o o c r ,
I
I
R2C O O C H
+ R
3
C O S C
0
A
f t
R2C O O C H
+ C oA SH
I
I
H 2C O H
A cyl-C oA
H
2
C O O C R
3
D iacy lg ly céro l
T riacy lg ly cero l
In a minor alternative pathway, triacylglycerol is syn-
thesized from glycerol-3-phosphate and acyl-CoA by es-
terification at the
1
,
2
-positions of glycerol, removal of the
phosphate group, and esterification at C
3
(Chapter 19).
The triacylglycerols are incorporated into a heteroge-
neous population of spherical lipoprotein particles known
as
ch ylo m icro n s
(diameter, 75-600 nm) that contain
about 89% triacylglycerol,
8
% phospholipid, 2% choles-
terol, and 1% protein. Phospholipids of the chylomicron
arise by
de novo
synthesis (Chapter 19) or from reacyla-
tion of absorbed lysolecithin. Cholesterol is supplied by
d e n ovo
synthesis (Chapter 19) or is absorbed. The protein
apolipoprotein B-48 (apo B-48) forms a characteristic
protein complement of chylomicrons and is synthesized in
the enterocyte. Synthesis of apo B-48 is an obligatory step
in chylomicron formation. Absence of apo B-48 synthe-
sis, as in the rare hereditary disease
abetalipoproteinemia,
leads to fat malabsorption. Enterocytes are involved in the
synthesis of other lipoproteins (Chapter 20).
S ecretion
Vesicles that contain chylomicrons synthesized within
the endoplasmic reticulum and the saccules of the Golgi
apparatus migrate toward the laterobasal membrane, fuse
with it, and extrude the chylomicrons into the intersti-
tial fluid, where they enter the lymphatic vessels through
fenestrations. Medium-chain triacylglycerols are absorbed
and transported by portal blood capillaries without for-
mation of micelles or chylomicrons. Chylomicrons en-
ter the bloodstream at the left subclavian vein via the
thoracic duct. In the bloodstream, they are progressively
hydrolyzed by endothelial lipoprotein lipase activated by
apolipoprotein C-II. Fatty acids so released are taken up
by the tissues (e.g., muscle and adipose) as blood passes
through them. The chylomicron remnants consist primar-
ily of lipid-soluble vitamins and cholesterol (and its esters)
and are metabolized in the liver. Chylomicrons normally
begin to appear in the plasma within
1
hour after ingestion
of fat and are completely removed within 5-8 hours (see
Chapters 18-20).
D iso rd ers o f L ip id D ig estio n a n d A b so rp tio n
Normally more than 95% of ingested lipid is absorbed.
When a large fraction is excreted in the feces, it is called
steato rrh ea .
Measurement of fecal lipid with adequate
lipid intake is a sensitive indicator of lipid malabsorption.
Malabsorption can result from impairment in lipolysis
(Table 12-6), micelle formation (Table 12-7), absorption,
chylomicron formation, or transport of chylomicrons via
the lymph to blood.
G en era l M a la b so rp tive P roblem s
A malabsorptive disorder caused by proteins found in
wheat, rye, and barley produces chronic sensitivity that
damages the small intestine in susceptible individuals.
This disorder is known as
g lu ten -sen sitive en teropath y
or
celia c disease.
The toxicity of the cereals are associated
with a group of proteins known as
g lia d in s
that leads to
production of antibodies to endomysium of smooth muscle
(Chapter 21). The damage to the small bowel consists of
conversion of normal columnar mucosal cells to cuboidal
cells, villous flattening, crypt hyperplasia, and infiltration
of lymphocytes and plasma cells into the lamina pro-
pria. Celiac disease has characteristics of an autoimmune
disorder associated with a genetic predisposition. High-
risk populations for celiac disease include patients with
Down’s syndrome, insulin-dependent diabetes, those with
