NEC White Paper
Scientific & Regulatory Affairs
Oligosaccharide Enzymes In Sugars Management
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by Danielle Harrison, Manager of Scientific and Regulatory Affairs
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NEC White Paper
October 2012
Oligosaccharide Enzymes In Sugars Management
by Danielle Harrison, Manager of Scientific and Regulatory Affairs
O
ligosaccharides are polymers of simple sugars (monosaccharides). Polymers of between two and ten sugar units are generally
classified as oligosaccharides, and longer polymers are generally
classified as polysaccharides. The same types of enzymes produce
both oligosaccharides and polysaccharides. Oligosaccharide enzymes
are the enzymes that generate both. This discussion will focus on
enzymes that generate fructose polymers (fructo-oligosaccharides or
FOS) and glucose polymers (gluco-oligosaccharides (GLOS).
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These polymers perform a variety of functions in living organisms
and are often attached as side chains to proteins and lipids. They are
especially common in vegetables and cold weather grains such as
wheat and barley. In humans, the digestible oligosaccharides such as
sucrose and starch are a source of energy and blood glucose because
our bodies have enzymes to digest and absorb them. The oligosaccharides and longer polymers such as cellulose that we can’t digest
are classified as fiber by food scientists. Non-digestible oligosaccharides may have beneficial effects on constipation, mineral absorption, lipid metabolism, cancer prevention, hepatic encephalopathy,
glycemia/insulinemia, and immunomodulation (Sweenen, 2006).
Unfortunately, processed food often contains more easily and rapidly
digestible oligosaccharides and simple sugars such as glucose and
fructose than we need. The potential consequences of a steady diet
of these easily digestible sugar sources are weight gain and excessive
blood sugar absorption. Emerging science associates these conditions with higher risk of digestive problems, obesity, dyslipidemia,
type II diabetes, liver disease, cardiovascular disease, cancer, and a
weakened immune system. It is interesting that these are almost
exactly the beneficial areas of non-digestible oligosaccharides.
Consumption of more oligosaccharide producing enzymes along
with meals is one tool that may be beneficial in glucose and weight
management. There are currently two oligosaccharide producing
enzymes with New Dietary Ingredient (NDI) applications on file with
the US FDA. These are Transglucosidase and Levansucrase.
Transglucosidase is an enzyme that works in a very similar manner
to glucoamylase (amyloglucosidase). Glucoamylase breaks down
starch by cleaving the saccharide bonds of glucose and releasing
glucose. Transglucosidase does the same thing initially, but instead
of simply releasing the glucose, it attaches the glucose to another
saccharide containing molecule. This can be a monosaccharide such
as glucose, or another saccharide polymer. The selectivity is driven by
the relative target concentrations, the three-dimensional structure of
the enzyme, and the size of the target molecules. Different transglucosidase enzymes can produce different bonds and have different
preferences. If you were to measure the glucoamylase activity in
the standard USP/FCC units, you could not distinguish between a
glucoamylase enzyme and a transglucosidase enzyme because the
assay only measures the breakdown of the glucose bond, not where
the glucose breakdown product ends up. Similarly, transglucosidase
activity in the USP/FCC amylase assays would not be distinguishable
because those assays only measure the destruction of the starch
complex, not what results.
The particular transglucosidase that is currently available for supplementation is of interest because the bond formation it catalyzes is of
a structure that is difficult for humans to digest and absorb. When
starch is consumed with this enzyme, it removes some of the glucose
from the starch complex and attaches it to a glucose containing
molecule. This glucose-glucose bond is resistant to digestion. This
effectively makes the glucose removed from the starch not digestible
by our bodies as well as the glucose it attaches to. If it is not digested,
it is not absorbed. If it is not absorbed, it reduces glucose absorbed as
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NEC White Paper
well as the calories absorbed. The bound glucose then also contributes
to the fiber load.
The benefits of adequate fiber are well known in health and weight
management, but the benefits as a prebiotic are less well known. The
non-digestible oligosaccharides are available to support the growth
of healthy probiotic bacteria in our intestines which have evolved to
exploit this unused resource synergistically. So by ingesting transglucosidase enzymes with starch, you effectively reduce the glucose
available for absorption, reduce the calories available for absorption,
increase the fiber content of your intestines, and support the healthy
flora in your intestines.
An interesting formulation opportunity arises from the fact that transglucosidase will polymerize the glucose with other monosaccharides
and saccharide polymers. If other digestive enyzymes are included in
a formula to speed the release of both the starch and other potential
receiving substrates, it should increase the opportunity for tying up
additional glucose. This is because more starch will be available as an
input and there will be a higher concentration of targets to bond the
glucose.
The inter-related reactions, substrates, and reaction products can get
pretty complicated, but the bottom line is that adding oligosaccharide
enzymes to a meal should reduce the sugars and thus the calories absorbed. This was demonstrated in at least two human clinical studies
with the transglucosidase enzyme.
The potential health maintenance benefits of the oligosaccharide
producing enzymes makes them a useful tool in the enzyme arsenal,
especially for people concerned about sugar management, weight
management, fiber intake, and general health management. They
also make useful adjuncts to probiotic products, weight management
products, and digestive support products.
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The other oligosaccharide producing enzyme that currently has an
NDI is levansucrase. Levansucrase removes a fructose from the dissaccharide sucrose and attaches the fructose to an oligosaccharide.
Differententiating Levansucrase by USP/FCC assays is similar to the
situation with glucoamylase and transglucosidase. Levansucrase and
invertase (sucrase) activity cannot be distinguished by the USP/FCC
invertase assay, because the assay only measures the rate in terms of
glucose produced. It doesn’t look at whether fructose is released or
where it goes. The particular levansucrase available with an NDI can
use some other fructose containing sugars as substrates as well, buts
its activity is quantified in terms of levansucrase. The additional sugar
side activities makes it more useful. This levansucrase also produces
non-digestible oligosaccharides like the transglucosidase, tying up
the fructose from the sucrose molecule while releasing the glucose.
As with the transglucosidase, this effectively reduces the sugar easily
available for absorption. Reduced sugar absorbed results in fewer
calories absorbed. The resulting digestion resistant oligosaccharide
increases the intestinal fiber levels and supports probiotic growth.
Like transglucosidase, similar synergistic opportunities are available
in formulations with other digestive enzymes. In addition, a combination of transglucosidase and levansucrase may also be synergistic,
since glucose and fructosyl oligosaccharide produced by the levansucrase can be receptors for the glucose from transglucosidase, and
remnants of the starch polymer and glucosyl oligosaccharide from the
transglucosidase reaction can be receptor substrates for the levansucrase reaction.
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