Directions: After students have had a chance to review the article “Small intestine is first stop for fructose,” lead a classroom discussion based on the questions that follow.
1. What are isotopes and how can they be used to label chemical molecules?
An isotope is a form of an element that’s nucleus has the same number of protons (and hence is the same chemical element) but a different number of neutrons (and therefore a different molecular mass). Isotope names include a number that indicates that isotope’s mass — how many protons and neutrons are in its nucleus. Molecules, such as fructose or glucose, can be labeled by substituting atoms of a certain element in the molecule with a different isotope of that element. Then, when the molecule is sent into a chemical reaction or an organism, the isotope label can be used to track the fate of that molecule. The most common elements in biomolecules are carbon, oxygen, hydrogen, nitrogen and phosphorus, so isotopes of those elements are especially useful for labeling biomolecules. For example, most carbon is carbon-12 — carbon with a mass of 12 atomic mass units — but carbon-11, carbon-13 and carbon-14 are available as labels.
2. How is mass used to identify and track isotopes?
A technique called mass spectrometry, which identifies molecules by their mass and electric charge, can be used to distinguish molecules of the same chemical type that contain different isotopes. In a mass spectrometer, typically a sample is vaporized and ionized, and the resulting individual charged molecules are accelerated by an electric field, deflected by a magnetic field and detected by sensors some distance away. The time of flight from the accelerator to the sensors, and the amount of deflection by the magnetic field, indicate the mass-to-charge ratio of the molecules. Molecules of completely different types will appear well separated. Molecules of the same chemical type but containing different isotopes will appear close together but with measurable differences in their masses.
3. How is radioactivity used to identify and track some isotopes?
Some isotopes undergo a form of radioactive decay known as beta decay. Radioactive isotopes that are useful for labeling biomolecules generally undergo one of two types of beta decay. In beta-minus decay, a neutron becomes a proton and emits a high-energy electron and an antineutrino. In beta-plus decay, a proton becomes a neutron and emits a high-energy positron (also called an antimatter electron) plus a neutrino. (See the Science News article, “The quest to identify the nature of the neutrino’s alter ego is heating up” for more information on beta decay.) Researchers measure the energy associated with these emitted particles to track the isotopes. Neutrinos are difficult to detect with current technology. But Geiger counters and other radiation detectors can measure high-energy electrons that travel short distances through certain materials. Positrons rapidly produce two gamma rays going in opposite directions that can be detected by gamma sensors and imagers. Those rays are especially useful for positron emission tomography (PET), which is used to image the inside of the human body. By carefully measuring the direction and time of arrival of each gammy ray in each pair that escapes from deep inside the human body, researchers and medical professionals can pinpoint the location of the decaying isotopes.
For labeling with radioactive isotopes, it is desirable to choose an isotope with a half-life that is neither too short nor too long. An isotope with a very short half-life would decay away before it could be detected once administered to the organism or system being studied. And an isotope with a long half-life might not decay and give off signals within the timeframe of the experiment.
CHEMICAL AND BIOLOGICAL SCIENCES
1. What are sugars (or saccharides)? Using sucrose as an example, describe how mono-, di- and polysaccharides are different.
Sugars, or saccharides, are organic molecules composed of carbon, hydrogen and oxygen, usually with chemical formulas at or near the proportions of CnH2nOn, where n is some integer greater than or equal to three. Names of different sugar molecules generally end in “-ose.” Monosaccharides, or simple sugars, are composed of one sugar molecule and typically have a few carbon atoms in a chain or ring. Fructose and glucose are two common six-carbon monosaccharides that have the same numbers of carbons, hydrogens and oxygens (C6H12O6) but somewhat different molecular structures. Disaccharides are composed of two linked monosaccharides. Sucrose is a disaccharide composed of one glucose molecule chemically bonded to one fructose molecule. Polysaccharides are composed of multiple chemically linked saccharides. Starch is a polysaccharide composed of many linked glucoses.
2. What is fructokinase?
Fructokinase is an enzyme found in the small intestine, liver and kidneys. A negatively charged phosphate group on fructokinase attaches to fructose, which helps keep fructose temporarily trapped within a certain organ. The attachment of the fructokinase to glucose also allows for passing the sugar along to other enzymes for further processing, or for pulling it apart to completely metabolize it.
3. What is aldose reductase?
Aldose reductase is an enzyme that is located in the liver and a variety of other tissues that are not organs. It converts glucose to sorbitol, which can then be converted to fructose by the enzyme sorbitol dehydrogenase. If the concentration of glucose in the body is too high, aldose reductase and sorbitol dehydrogenase convert some of the excess glucose to sorbitol and fructose, which may contribute to tissue damage over a prolonged period of time. This is why monitoring blood glucose levels in humans with diabetes is important.
4. What is the hepatic portal vein?
The hepatic portal vein carries blood from the small intestine to the liver. Through the vein, blood transports molecules that have been absorbed through the intestinal wall to the liver. Enzymes in the liver metabolize nutrients that are then stored or passed on to the rest of the body as required. Other liver enzymes convert toxins that were absorbed along with those nutrients into less toxic forms.
ENGINEERING AND EXPERIMENTAL DESIGN
1. How could similar studies be performed in humans, or in other animals larger than mice?
In mouse experiments, organs can be removed for analysis. In humans, one might be able to analyze the amount of fructose or its metabolites in a blood sample taken from the vein between the small intestine and liver, if that could somehow be done safely. Analyzing biomolecules in urine and stool samples is also possible, although such tests may not provide certain kinds of information. It might be possible to put miniaturized chemical sensors in the gastrointestinal tract or elsewhere in the body. Small amounts of radioactivity could be used to track labeled molecules; positron emission tomography (PET) is especially useful. Magnetic resonance imaging (MRI) could also track molecules with various isotope labels. While PET and MRI could follow certain isotopes inside a patient, they could not readily distinguish if those isotopes are still part of the original molecules or if they have become incorporated into new types of molecules. Conducting experiments on animals intermediate in size between mice and humans, such as monkeys, could help address the issue of scaling up the mice data.
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