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Transcript
IV
Human Lipid Digestive Enzyme System
Why Those suffering From Malnutrition and Those Less Than
Two Years Old Can Benefit From Pre-digestion of Their Food
Lipids are essential for health and normal development. They
store energy in the body. Animals use triglycerides for energy
storage because of its high caloric content as compared to the less
compact carbohydrates utilized in plants. Lipids are major
components of cell membranes. They are essential for normal brain
development and maintenance as well as the neurological system
in general. Linoleic and alpha-linoleic fatty acids are essential
because they can not be synthesized by the normal human body.
Cholesterol is the base molecule for bile salt production.
Cholesterol is also a precursor of steroid hormones. Lipids are
necessary to solubilize fat soluble vitamins for absorption.
To understand lipid digestion, one of the things that needs to
be understood is the process of emulsification (making an
emulsion). An emulsion is the suspension of small globules of one
liquid in a second liquid with which the first will not mix. An
example is the mixture of vinegar and oil. In the intestines it is
lipid and water. They will stay mixed only as long as they are
stirred together unless an emulsifying agent or emulgent is present.
Bile salts are emulgents. Bile acids are derivatives of
cholesterol and are produced in the liver. These acids are
constituents of bile which is produced in the liver and delivered to
the duodenum (the first part of the small intestines). Here these bile
acids are converted to bile salts by the alkaline or basic
environment of the duodenum. Part of the bile salt is hydrophilic
(attracts water) and part is hydrophobic (repels water). When bile
salts come in contact with lipids, the hydrophobic parts bind into
the lipid with the hydrophilic part remaining at the surface. This
allows the break down of large aggregates or droplets of the lipid
1
into smaller and smaller droplets (micelles) in the water
environment of the duodenum. For any given triglyceride volume,
the smaller the micelles, the greater surface area of triglyceride
available for digestive enzyme activity.
About 90% of the bile acids are reabsorbed in the ileum, the
last part of the small intestines. This is known as enterohepatic
circulation. On the average, about 25 grams of bile salts are
delivered to the small intestines daily. Therefore, about 2.5 grams
of bile salts in the adult are produced by the liver on a daily basis
and 22.5 grams are reabsorbed daily. Diarrhea significantly
interferes with enterohepatic circulation, resulting in loss of bile
salts and, therefore, over time, fat digestion. This results in
increased diarrhea secondary to malabsorption of the lipids. A
vicious cycle is created.
Lipids are fats, oils, phospholipids, and sterols. Fats are
triglycerides containing saturated fatty acids. Fats are generally
solid at room temperature and are from animals. Oils are
triglycerides containing mono or polyunsaturated fatty acids
usually from plants and fish. They are liquid at room temperature.
A triglyceride is made up of glycerol with three attached fatty
acids:
H2C – Fatty Acid
l
HC – Fatty Acid
l
H2C – Fatty Acid
Phospholipids are triglycerides that have a fatty acid replaced by a
phosphate linked fatty acid group. The major dietary sterol is
cholesterol
Lipases are enzymes that digest lipids. In the human, there
are lipases which are produced in the tongue, the stomach and the
pancreas. Stomach and lingual lipases hydrolyze or digest a limited
number of fatty acids. The lipases produced by the pancreas are the
2
major lipases utilized in lipid digestion in the adult. Pancreatic
lipases will be discussed first.
Pancreatic lipases are secreted by the pancreas in their active
forms. There is a second protein that is secreted by the pancreas in
conjunction with lipase. This is a protein co-factor required for
optimal enzyme activity of pancreatic lipase, facilitating binding of
the pancreatic lipases at the lipid water interface. It is called
colipase. Colipase is secreted in an inactive form and is activated
in the duodenum by trypsin.
Lipases are water soluble enzymes that catalyze the
hydrolysis (breakdown) of water insoluble lipid substrates (made
possible by the bile salt interactions forming micelles as described
above). Lipase acts to convert triglycerides to a monoglyceride and
two fatty acids. The sequence is as follows:
Bile Salts (mechanical digestion)
digestion)
l
Lipase (chemical
l
Fatty
acids
Large fat droplets -------------------------small fat droplets-------------------monoglycerides
glycerol
[1].
A pancreas produced lipase called phospholipase hydrolyzes
phospholipids into a glycerolphospholipid + two free fatty acids.
Another lipase called glycerolphospholipase separates the
remaining molecule of glycerolphospholipid into glycerol and a
fatty acid. These products then are able to be absorbed by the small
intestines.
3
Cholesterol also is included in the micelles where a lipase
called cholesterol esterase removes a fatty acid from the
cholesterol molecule, thus making both available for absorption.
Lipases are also produced by the salivary glands of the
tongue and by the stomach, lingual and gastric lipase respectively.
There are several differences from the pancreatic lipases in
addition to their sites of production. These lipases are functional at
lower pH than the pancreatic amylases that function in the basic
environment of the duodenum. Gastric lipase works optimally at a
pH of 3 to 6 [2], and lingual lipase at 4.5 to 5.4 [3]. Neither require
colipase or bile salts to function As much as 20% of fat digestion
can occur as a result the actions of gastric and lingual lipases, with
the majority of this activity being the result of gastric lipase [2].
These acid lipases, however, are much less efficient than the
pancreatic lipases. They only separate one fatty acid from the
triglyceride. The free fatty acid is absorbable, but the residual
diglyceride is not
The production of pancreatic lipase is age related. Pancreatic
response to hormonal secretory stimulation is absent or minimal at
birth up to about age six months. After six months the response
increases and is normal by age two [4,5]. Bile salt is also deficient
in newborns. Breast milk does contain lipase and bile salts which
accounts for 2/3 of the lipid hydrolysis in the newborn [15]. Those
who are weaned early do not have the advantage of breast milk
digestion of lipids, losing a significant amount of the lipid derived
products necessary for cell wall structure, tissue development, and
specifically brain growth and development.
The lingual and gastric lipases are present at birth. Although
this digestion of lipase is not as efficient as the pancreatic lipases,
it does provide some lipid digestive products for absorption and
utilization. In infants, these lipases provide up to 50% of lipolytic
activity [2]. As a result, the absorptive rate of dietary fat by young
infants can be as low as 65 % of that of the adult [3].
With malnutrition, all of the pancreatic enzyme activity is
reduced, including lipase [7]. The size of the pancreas significantly
4
decreases in conjunction with the decrease in enzyme production
[8]. In addition, the lining of the small intestines flattens and the
mucosa is hypoplastic (reduced cellular production). This results in
malabsorption due to increased amounts of sugar and fat remaining
in the intestinal lumen. This, then, secondarily results in bile salt
loss which compounds the effects of malabsorption and the
resulting diarrhea [9]. Correction of malnutrition results in the
pancreas and the small intestines returning to a normal state. This
takes a few weeks [8]. In cases of pancreatic insufficiency other
than as a result of malnutrition, the lingual and gastric lipases help
compensate for pancreatic lipase deficit. The reason for decrease
production of pancreatic enzymes in malnutrition is due to the
inability to manufacture protein. Protein is actually broken down
for energy production. This, no doubt, affects the enzyme
(protein) production by the tongue and stomach as well as by the
pancreas.
Lipase is an active enzyme in barley malt. It is reasonably
heat stable, surviving mashing [11,12]. Kilning, which has a peak
temperature of 70 degrees centigrade, results a reduced lipase
activity by about 10%. The optimal pH range of activity is between
4.0 and 5.0 [14], making it suitable for pre-digestion of the starchbased foods commonly used in the developing world. Because of
this, the use of barley malt flour to predigest the common porridges
and gruels of the developing world will provide essential products
of lipid digestion for absorption by the intestines of weanlings,
young infants and malnourished people of all ages that otherwise
would not be made available to them.
It is of note that it became obvious to those conducting the
double blind study utilizing PowerFlour in Panama which children
were receiving barley malt enhanced food. They were the ones
whose diarrhea quickly resolved. This occurrence was most likely
due to the fact that the pre-digested carbohydrate, protein and
lipids were able to be absorbed , and, thus, removed from the
gastrointestinal tract. The carbohydrate, protein and lipid in the
5
non-treated group remains in the gastrointestinal tract, resulting in
the diarrhea commonly seen with malabsorption.
BIBLIOGRAPHY
1 – Class Notes on Digestion – Accessed at
http://www.stout.edu/faculty/millerlou/CLASS%@)%@)DIGESTION.htm on 11/11/2008
2 – Gastric Lipase – Accessed at
http://en.wikipedia.org/wiki/gastric_lipase on 11/11/2008
3 – Lingual Lipase – Accessed at
http://en.wikipedia.org/wiki/lingual_lipase on 11/11/2008
4 – Development of Functional Response in Human
Exocrine Pancreas, Emanuel Lebenthal MD and P. C. Lee
PhD, Pediatrics Vol. 66, No. 4, October 1980, pp556-560
5 – Serum Levels of Immunoreactive Trypsin during
Development: Comparison with levels of Lipase and
Amylase, Colombo C., Malavacca R, Ronchi M, Bottani
P., Stripparo L, Corbetta C, and Sereni LP, Pediatric
Gastroenterology Nutrition Vol. 9, No. 2, August 1989, pp
194-9
6
6 – Rudolf’s Pediatrics – David Celin – p 1312 accessed at
http://books.google.com/books?id=0J6G3E1Y0EwC&pg=
PA1312&1pg=PA1312&dq=b on 11/19/2008
7 – First Principles of Gastroenterology, Chapter 2/4Effects of Malnutrition on the Gastrointestinal Tract and
Pancreas, pp60-1 Accessed at
http://www.gastroresource.com/gitextbook/En/Chapter2/24.htm on 11/11/08
8 – Pancreatic size in Protein Energy Malnutrition: a
Predictor of Nutritional Recovery, El-Hodhod M. A.,
Nassar M. F., Hetta O. A., and Gomaa S. M., European
Journal of Clinical Nutrition, Vol. 59, No. 4, pp 467 – 73
9 – Digestive and Absorptive Phase Anomalies with the
Exocrine Pancreatic Insufficiency of Cystic Fibrosis,
Claude C. Roy, Andree M. Weber, Guy Lepage, Lesley
Smith, and Emile Levy, Journal of Pediatric
Gastroenterology and Nutrition, Vol. 7, Suppl. 1,
November 1988, pp1-7
10 – Saliva and Gastrointestinal Functions of Taste,
Mastication, Swallowing and Digestion, Oral Diseases,
Vol. 8, No., published on line on 3May2002, pp117-29
11 – Activity of Lipase During Mashing, Paul Schwartz,
Patriciz Stanley, and Sean Solberg, Journal of the
American Society of Brewing Chemists, Vol. 60, No. 3,
2002, pp 107-09
12 – Activity of Lipase during Malting and Mashing –
ASBC 2001 Meeting Abstract, p 13, Accessed at
http://www.asbcnet.org/meetings/2001/Abstracts/P-13.htm
on 11/17/2008
7
13 – Grain: Composition and Functionality – Chad
Stevens, Quality Ale and Fermentation Fraternity, San
Diego, CA, Accessed at
www.quaff.org/SpeakerNotes/Grain_composition_Functio
nality-Chad-Stevens.pdf on 11/17/2008
14 – Introduction to Enzymes: Effects of pH – Accessed at
http://www.worthingtonbiochem.com/introbiochem/effectpH.html on 12/10/2008
15 – Current Pediatric Diagnosis and Treatment – William
W. Hay, Anthony Hayward, Myron J. Levin, and Judith M.
Sondheimer, pp 280 – 81, Accessed at
http://books.google.com/books?id=hoa4CnJdQ1C&pg=PA280&1pg=PA280&dq=bile+sa on
11/19/2008
8