NEC White Paper

Scientific & Regulatory Affairs

Oligosaccharide Enzymes In Sugars Management

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 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

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). 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 cant 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

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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 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 doesnt 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
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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. 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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