ChemCases.com
Directory
ChemCases.com Home
Concept
Map 1
Concept
Map 2
Back to Olestra 5. Lipids
Back to Olestra 7. Fat Metabolism
Ahead
to Olestra 9. FDA Approval ProcessChemical
Concepts
Fats play a
significant and unique role in bodily function.
| 14.
Molecules with 4-8 fatty acid residues |
are
not hydrolyzed by |
lipases |
| 1. Energy available |
can be determined from |
The type and amount of food we eat |
| 2. Enzymes |
enable
our bodies |
to metabolize foods |
| 3. Intermolecular forces |
explain |
the fate of fats, fat substitutes
and vitamins in our bodies |
| 4. Proteins |
are
assembled from specific sequences of |
Simple amino acids |
| 5. Proteins |
assemble
into |
Uniquely shaped structural masses |
| 6. Uniquely shaped proteins called
enzymes |
bind
to |
Other molecules and speed chemical
rections |
| 7. Enzymes called lipase |
speed
or catalyze |
Breakdown of fats |
| 8.
Enzymes |
lower |
Activation
energy necessary for reaction |
| 9.
Fats |
are
our |
water
insoluble energy reserve |
| 10.
Edible fat unsaturation |
correlates
with |
melting
point and oxidation |
| 11.
Carbohydrates and proteins |
produce |
16-17
kJ/gram of energy when oxidized |
| 12.
Fats |
produce |
about
38 kJ/gram when oxidized |
| 13.
Specific stomach enzymes - lipases |
catalyze |
conversion
of fats to soluble bile salts |
We will see
how researchers used these simple chemical concepts to
invent and develop olestra and we will use these
principles ourselves to evaluate and decide on
nutritional issues
Fred
Mattson and Robert Volpenhein first studied this
triglyceride hydrolysis process in detail and then they
continued this study with molecules that contained from
one to eight alcohol/fatty acid bridges rather than the
three that exist in triglycerides. This led to some very
unexpected results that are discussed in
this section of this ChemCases.com unit. Unexpected
results are the basis for a patent.
| Patent
Case Discussion: Fred Mattson worked for
Proctor & Gamble when he first studied the
effect of sucrose fatty acid esters.
He recognized that these materials were new,
novel and unexpectedly did not hydrolyze in test
animals. These three requirements, novelty,
usefullness and unexpected or unobviousness are
the requirements for obtaining a US patent.
The US Patent and Trademark Office posts US
patents on the internet and you can read
Mattson's original description of his work in his
patent. Please
notice two things.
- First, the asignee is Proctor &
Gamble. That means that although
Mattson did the original work, his
employer owns the patent and any
financial benefit that might accrue. Is
this fair? Is Mattson compensated
adequately by being employed and
presumably paid in relationship to his
contribution to his employer? How
would you arrange a payment system for
your creative employees?
- Second, look at the section of the patent
called the claims. The claims
describe what the inventor (or his/her
assignee) owns. In this case,
P&G owns "a composition of
matter comprising . . .
a non-digestible polyol fatty acid
polyester ... ." A
compositon of matter claim means that no
one else can make, use or sell that
compositon without your permission during
the life of the patent. If the
inventor writes the claims well, they are
a powerful legal restriction against
others interfering in the development of
an invention. How long
should a patent be in force? Is it
a good idea to allow a patent to be
enforceable forever? What would
make good sense?
|
| Would you like to
try the Unexpected Results Quiz to analyze what
Mattson and Volpenhein discovered?
|
|
|
Olestra 8. - Early
Research on Lipid Metabolism Leads to Olestra Lipid Metabolism Mechanism
Research with Sucrose Esters
Properties of Olestra
The
discovery and development of Olestra was typical of many
scientific discoveries. The initial research was seeking
answers to another question, and the results of the
investigations, coupled with a creative approach and
interpretation led to a completely new set of
applications and products.
| Concept: Chemical research
uses principles we learn in general
Chemistry. We study chemical kinetics - the
rates of chemical reactions. And we
recognize when catalysts such as the enzymes
speed up these reactions. Here is a case where
scientists at Proctor & Gamble observed that
enzyme-catalyzed hydrolysis reactions were not
taking place as they had expected. the
reactions were unexpectedly slow. From this
observation came the development of olestra.
|
Lipid Metabolism
Mechanisms: The initial research at Procter &
Gamble was looking at two areas, Basic lipid metabolism
research, and the digestion and metabolism of
monoglycerides. The monoglycerides were being studied for
uses as emulsifying agents to help hydrophyllic (water
loving) and lipophyllic (fat loving) substances mix
together better in some of the many food products created
at Procter and Gamble. The lipid research was
fundamental, looking for a greater understanding of the
fat splitting actions of the pancreatic lipase enzymes.
The
mechanism of fat absorption was not completely understood
and included the incorrect assumption that some dietary
fat was absorbed from the intestine as intact, emulsified
triglyceride droplets. Two Procter and Gamble scientists,
Fred Mattson, and Robert Volpenhein, completed laboratory
research that led first to these important initial
understandings of triglyceride metabolism and then
applied and extended this information to create a
non-absorbable fat, Olestra.
The
first major step in their research was to determine the
mechanism for the hydrolysis of the fatty acid chains
from the typical edible fats, the triglycerides. They did
this by using specially manufactured and purified olive
oil triglycerides that had been labeled with carbon 14 so
that the products and where they had come from could be
exactly identified.
| Concept: The
ChemCases.com unit on nuclear
chemistry introduces you to the special
transformations of the nucleus. One of
these is the spontaneous decay of isotopes of
elements to give radiation. Many of the
common elements posess small, naturally occurring
amounts of these unstable isomers. Carbon
is one of them and carbon atoms with an atomic
weight of 14, C14, emit measurable
radiation. We
have learned to use this radiation to locate
specific carbon atoms in chemical
reactions.
Suppose we are able to make a compound, let's
say oleic acid, with an overabundance of C14
at the acid end -(C14=O)O-.
Then we carry out chemical transformations on the
molecule, including chemical reactions and
separations and identification of the products.
When we observed the macroscopic phenomenon of
the radiation in one fraction of the separated
materials we would know that the specific carbon
atoms that had once been at the acid end of the
chain were now in that fraction.
With this observable information we can begin
to develop a mechanism on the molecular scale of
how the transformatin we are studying takes
place.
Once again we illustrate the point
that chemistry relates observable phenomena to
understand molecular properties, then uses
molecular inferences to develop observable ideas.
|
They also used a variety of pancreatic
lipase enzymes. Some of these mixtures contained only the
lipase that was specific for breaking the ester linkages
at the first and third positions. Others contained both
this specific enzyme and a non specific enzyme that would
also hydrolyze the ester linkage in the second position,
but at a slower rate. The significance of this work is
that it began to unlock the details of this hydrolysis
process.
Research on the
Sucrose Esters: In a second step of their
research, which led to the creation of Olestra, Mattson
and Volpenheim created and studied a series of molecules
that contained from one to eight alcohol/fatty acid
linkages. They did this by synthesizing in the
laboratory, esters based on a series of fatty acids
combined with a series of "polyols" - molecules
that contain many alcohol (-OH) groups. We are
familiar with many polyols - the common sugars, for
example, glucose, fructose, sucrose, are polyols.
After
creating these molecules they studied the hydrolysis of
the compounds in mixtures of the enzymes and then the
absorbability of these compounds when they were fed to
rats. The results were as expected at first, the rate of
hydrolysis and absorbability increased as one, two, or
three ester compounds were studied.
Beyond
three alcohol groups in the polyol, the unexpected
occurred. As the compounds with four through five carbons
were studied the hydrolysis markedly decreased and for
the compounds with six, seven, or eight ester groups, no
hydrolysis at all occurred.
This
discovery indicated that a fat could be prepared that
would not be hydrolyzed or digested. After many years of
study this led to the current mixture of esters, mostly
sucrose octaoleate, that make up olestra.
Properties of Olestra: While Olestra
provides no calories, It has many properties of the
typical edible fats and oils. Remember that the length
and degree of saturation of the fatty acid chains dictate
the properties of fats. Olestra produced from
polyunsaturated fatty acids produces at room temperature
a clear liquid oil, while Olestra from saturated fatty
acids yields an opaque solid allowing a variety of
possible uses.
Proctor
& Gamble developed a fat substitute that met the
requirements for safety and listed these specifications
for Olestra as part of the FDA approved petition:
- That
the total content of Octa-, Hepta-, and
Hexa-esters is not less than 97 %, that the
content the Octa-ester is at least 70 % and that
the content of the Hexa- and penta-esters is not
greater than 1% and .5%, respectively. This
specification insures that the Olestra is
composed of the higher ester groups that are not
digested.
- That
the unsaturated fatty acid content is not less
than 25 % and that the saturated fatty acid
content will be no greater than the 75% of the
total content.
- That
the content of C12 and C14 fatty acids is not
greater than 1% each, that the total of C20 and
longer fatty acids is not greater than 20%, and
that C16 (Palmitate) and C18 (Stearate) fatty
acids will comprise at least 78% of the total.
These specifications dictate the physical
properties of the Olestra blend, especially the
melting point and consistency.
Other
specifications govern the overall purity of Olestra and
dictate the content of free fatty acids at not greater
than .5%, the total methanol content at not greater than
300 parts per million(ppm), the total heavy metal content
at not greater than 10 ppm, and that lead content is not
greater than 0.1 ppm.
Space
filling model of olestra. We show a model of
sucrose with eight oleic acid ester groups. The fat
substitute compound will have a mixture of many similar
molecules
Copyright
© 1997 by Daniel J. Berger. This work may be copied
without limit if its use is to be for non-profit
educational purposes. Such copies may be by
any method, present or future. The author requests only
that this statement accompany all such copies. All rights
to publication for profit are retained by the
author.
Olestra
is the product of both basic chemical research and a
company looking to make innovations to the variety of
food products available. The creation of this product
marked only the beginning of a long and complicated
process to find potential uses and markets for Olestra.
It also marked the beginning of a huge effort to prove
the safety and benefits of this product. To look at some
of the details of this process go back to the Olestra
Concept Map and continue with the Issues and FDA
approval process.
|
