Hydrolysis of sucrose produces an equimolar mixture of glucose and fructose,that is sweeter than sucrose itself. Since the specific rotation of these sugar solutions changes from +66.5º for pure sucrose to -22.0º for the hydrolysis mixture (fructose is strongly levorotatory), the resulting glucose fructose mixture is called invert sugar. It is widely used in food manufacture in much the same way as HFCS. An enzyme, invertase, which catalyzes the hydrolysis of sucrose in living organisms, is used in the manufacture of invert sugar. Honey is similar to invert sugar, consisting roughly of 38% fructose, 31% glucose, 9% disaccharides such as maltose and 17% water.
Although there is a strong correlation between the rise of obesity in the US and the use of HFCS for sweetening beverages and foods, it is not clear whether this is a causal relationship. In fact, no substantial evidence supports the idea that high-fructose corn syrup is responsible per se for obesity. Instead, over-consumption of sugars, encouraged by the low cost of HFCS and invert sugar, is the general culprit.
Insofar as the public is concerned, the sweet taste of sugars is undoubtedly their most important characteristic. In this respect, synthetic sweetening agents have become a multimillion dollar business, thanks to the national preoccupation with weight control. The structural formulas for five compounds of this kind are shown on the right, together with some of the commercial names under which they are sold. Saccharin was discovered in 1879 at Johns Hopkins University, and is the oldest member of this group. Sucralose is the newest sweetener, with FDA approval being issued in 1999.
Because the synthetic sweeteners are many times sweeter than sucrose, only small amounts are needed to achieve a desired effect. Also, most are not significantly metabolized, so their use does not introduce additional calories into a diet. For some individuals, however, taste overtones such as bitterness reduce the suitability of these agents as sugar substitutes. If the sweetness of sucrose is taken as a standard, then these and other sweetening agents may be ranked accordingly, as listed below.
Aspartame is a dipeptide composed of two natural amino acids, phenylalanine and aspartic acid, neither of which is sweet. Each of these components has a stereogenic center, so four stereoisomers are possible. The natural configuration of these amino acids is 2S, and (S,S)-Aspartame is the commercial sweetener. The other three stereoisomers are not sweet, and one is bitter. Aspartame undergoes a slow intramolecular acylation to a cyclic dilactam that is not sweet. Consequently, soft drinks and other beverages that contain dissolved aspertame have a limited shelf life. This slow reaction is accelerated by heat, so aspertame is not suitable for cooking purposes. To see an equation outlining the intramolecular acylation click on the above diagram.
Acesulfame, cyclamate and saccharin are achiral, and are generally suitable for cooking Since these compounds are acidic, their water soluble sodium or potassium salts are the commonly used form. Sucralose has many stereogenic centers, and although other chloro derivatives of sucrose are also sweet, only the designated stereoisomer has been approved as a food additive.
For sweetness to be perceived, molecules of a substance must activate receptor sites in taste bud proteins on the tongue. This activation is believed to occur when a molecule of suitable shape has a characteristic functional distribution, referred to as the A, B, C system. According to present theory, there are three essential components to a sweetener molecule, oriented in a triangular fashion, as shown on the right. The A(H) and B regions encompass functions of higher electronegativity, and the distance between them must be greater than 2.4 A and less than 4.0 A. If the distance between the atoms are not in this range then the substance becomes bitter. The third part of this triangle, C, represents a hydrophobic and lipophilic region of the molecule, not a specific atom or group. This region does not bind to the receptor site. When a sweetener molecule binds to a receptor, the AH region of the sweetener hydrogen bonds to the B region of a receptor site, and the B region of a sweetener hydrogen bonds to the AH region of the receptor site. This triggers a response by cells in the taste bud, such that electrical impulses to the brain create the perception of sweetness.
Acesulfame, saccharin and cyclamate are partially protonated by saliva, generating the A(H) moiety. The adjacent SO2 group serves as the B region in the first two cases. Similarly, the zwitterionic aspartic acid segment of aspertame provides the A(H) and B sites for that sweetener. Sucralose and natural sugars are not as easily analyzed, but more advanced molecular orbital calculations have identified essential features in these compounds.
To examine molecular models of these sweetening agents Click Here.
Before any food additives, including synthetic sweeteners, become available for general use, they must be evaluated and approved by the FDA (Food & Drug Administration). .First, the immediate or acute toxicity of a substance is established by animal feeding studies. In this respect all the sweeteners listed above were determined to be relatively innocuous ( roughly 10 times less toxic than salt and 100 times less toxic than caffeine to rats ). It should be remembered that everything is poisonous when taken in a sufficiently high dose. Thus, quantities of 25 to 30g of caffeine in a single dose are lethal to most humans.
It is a relatively simple matter to establish the acute toxicity of a substance, so most of the FDA's effort is directed to discovering chronic toxicity and carcinogenic factors associated with a given agent. Such studies are conducted in a variety of government, pharmaceutical and academic laboratories, often over a relatively long time period, and require care in the interpretation of results.
Saccharin, the oldest of the synthetic sweeteners, has been the subject of more than 3000 separate studies. In the 1970's a report of increased incidents of bladder cancer in rats fed very large amounts of saccharin led the FDA to require that a warning label, "May be hazardous to your health." be carried on products containing saccharin. Rat bladder cancer was also reported in cyclamate feeding studies, and FDA approval was withdrawn in 1970. Later reviews suggested that the increased sodium load associated with the very high doses in these studies may have been responsible for some of the bladder cancer. Consequently, the warning requirement for saccharin was lifted in 1991. Cyclamate is likely to be approved soon; over 600 studies have been conducted, and it is presently approved for use in 55 other countries.
Over 700 studies of aspartame are reported. Unlike saccharin, cyclamate and acesulfame, which pass through our systems largely unmetabolized, aspartame is converted to phenylalanine aspartic acid and methanol. The first of these metabolites presents a danger to individuals having the genetic disorder PKU, which inhibits their ability to further metabolize this essential amino acid. Some concern has also been voiced concerning the methanol metabolite, but the small amounts produced in normal use are unlikely to pose a serious health issue (methanol is only 10% of aspartame). Aspartame received FDA approval in 1981. It is worth noting that there seem to be more anecdotal reports of health problems associated with aspartame than with the other sweetening agents, but this may only reflect its widespread use in soft drinks.
Sucralose, the newest and least studied sweetener (ca. 70 reports), received FDA approval in 1998. Although largely unmetabolized, over 25% of ingested sucralose is believed to be retained or metabolized to dichlorofructose. Reports of thymus gland shrinkage and liver enlargement will need to be investigated before being dismissed.
Stevia is a genus of herbs and shrubs native to subtropical and tropical South America and Central America. The leaves of the plant Stevia rebaudiana Bertoni have a sweet taste resulting from glycosides of the diterpene steviol (structure on the right).
Stevioside and rebaudioside A, the primary components, are glucosides attached to the hydroxyl functions of steviol. They are heat stable, pH stable, and do not ferment. Stevioside has a sweetness 200 to 350 times that of sucrose, and a relative caloric value 300 fold less. Since stevioside does not induce a glycemic response when ingested, it offers potential as a natural sweetener for diabetics and others on carbohydrate-controlled diets.
In South America, stevia leaves have been employed in ethnomedical applications for centuries. In Japan, stevia extracts have been used as a sweetener for over thirty years with no reported harmful effects. Nevertheless, in 1991, at the request of an anonymous complaint, the United States Food and Drug Administration (FDA) labeled stevia as an "unsafe food additive" and restricted its import. The FDA's stated reason was "toxicological information on stevia is inadequate to demonstrate its safety." The 1994 Dietary Supplement Health and Education Act forced the FDA in 1995 to revise its stance to permit stevia to be used as a dietary supplement, although not as a food additive – a position that seems contradictory because it simultaneously labels stevia as safe and unsafe, depending on how it is sold.
Additional studies have shown that stevia improves insulin sensitivity in rats, possibly promoting insulin production. Also, preliminary human studies suggest that stevia may help reduce hypertension. Despite other research pointing to the safety of stevia, government agencies continue to express concern over a lack of conclusive evidence on this subject.
Complex oligosaccharides are common components of numerous biologically important macromolecules. In many of these systems aminosaccharides, deoxysaccharides and C9 glyconic acids are found linked to more common sugar units, so an amazing diversity of similar but distinct structures exists. In this discussion we shall limit our attention to relatively simple molecules composed of simple aldohexose units.
Appreciable amounts of oligosaccharides are found in certain foods, such as peas and beans. The structural formulas of three such compounds are given in the following diagram. They are all non-reducing sugars. A common sucrose moiety is seen for the two rings on the right, and this is joined to one or more galactopyranose rings by alpha-glycoside bonds at C-6. Two enzymes are required to hydrolyze these oligosaccharides into monosaccharides that are easily absorbed into the blood stream. The galactose units are cleaved by alpha-galactosidase, and the glucose-fructose link in sucrose is hydrolyzed by sucrase (or invertase). Humans do not have a source of alpha-galactosidase in their digestive system, so the oligosaccharide passes largely unchanged into the colon. Anaerobic microorganisms in the colon ferment these sugars, producing carbon dioxide and methane, gases that cause flatulence.
An interesting class of non-reducing oligosaccharides composed of glucopyranose rings joined 1-4 by alpha-glycosidic bonds are called cyclodextrins. Cyclodextrins are formed when starch is treated with an amylase enzyme from Bacillus macerans. Depending on the number of glucose units in the ring the cyclodextrins are named alpha (6), beta (7), and gamma (8). The shape of the cyclodextrins is that of a tapered ring, with the C-2 and C-3 hydroxyl functions on one edge and the CH2OH groups hanging from the opposite edge. The structure of the beta-isomer is shown on the right. By clicking on this structure a model of this cyclodextrin will be displayed. Because the interior of the cyclodextrin ring is relatively hydrophobic, these remarkable compounds are able to encapsulate small nonpolar molecules. They have been used as catalysts and aqueous transport agents.