SENSE OF TASTE LLOYD N. FERGUSON and AETIUS R. LAWRENCE Howard University, Washington, D. C. GUSTATION AND FOOD FTAVORS
The sense of taste is a subject of wide academic interest, as well as one of popular fascination and practical importance. Deep aesthetic enjoyment is experienced through the sense of taste, and there are even those who live t o eat. I n recent years, more and more food has been processed for its preservation and for the convenience of the housewife. For public acceptance, the nutrients and, in particular, the flavor must be retained. The morale of men in the Armed Forces is heavily dependent upon the pleasure they derive from eating their food. Consequently, the food processing industry and the Quartermaster Corps of the Armed Forces are especially concerned about the control and modification of food flavors. There is also a continuous search for better nonfattening sweetening agents and artificial flavorings. It is interesting that the only two nonsugar sweetening agents permitted on the market by the Food and Drug Administration were discovered by accident. These are saccharin and sodium cyclohexysulfamate ("Sucaryl"').
Sgceharin
"Sucaryl"
There is another important reason for studying the sense of taste: something may be learned about the way chemicals stimulate biological activity. One of the factors which makes it difficult to correlate physiological actions of medicinals with their chemical constitution is that the place of administration of drugs (orally or by injection) is usually far from the site of biological action. A drug may have t o go through several processes (i.e., pass from aqueous t o lipoid media or vice versa, dissociate, hydrolyze, penetrate a semipermeable membrane, etc.) and the critical step determining the applicability of a given drug is very difficult to discern, if at all (1). Hence, most effective drugs are discovered by a modified "test-andsee" method. However, the site of taste stimulation is easily accessible (the tongue) and sapid substances merelv have to be in aaueous solution to elicit the physiological response of taste. Hence, in trying to understand how chemicals induce physiolo~icalactivity, it is advantageous t o study the sense of taste. I t can he seen, then, that there are aesthetic, military, Registered trademadt, Abbott Laboratories. 436
commercial, and academic reasons for learning as much as possible about the sense of taste. The acceptance of food depends upon its texture, odor, and taste. Appearance must be added as a criterion too, because green steak or purple potataee would have no appeal unless the public could be so conditioned. The volatile flavor-substances in foods stimulate olfactory and gustatory sensations, whereas nonvolatile substances such as sugar and salt stimulate only taste receptors. Contrary to popular belief, people without a sense of smell can still taste, although their taste perception is modified and reduced (2). The isolation and identification of suhstances responsible for food flavors may require hundreds of pounds of natural foods in order to obtain a few grams or milligrams of flavor components. The nonvolatile substances consist of sugars, hydroxy and amino acids, a few complex organic compounds, and salts. The volatile fractions usually contain aliphatic acids, aldehydes, ketones, esters, alcohols, arnines, and a few sulfur-containing compounds. In order to minimize structural changes of the initial constituents, isolations are carried out a t low temperatures and pressures, although some substances may be isolated by steam distillation or liquid extraction ($9). As in other areas, vapor chromatography has been extremely helpful in separating and purifying flavor-compounds. The mixtures are normally quite complex. For instance, vacuum distillation of roasted, dry coffee will yield a heat-labile, 'yellow oil from which more than 70 substances have been i s ~ l a t e d . ~Vapor chromatography has revealed the presence of over 30 constituents in strawberry oil (3). The immediate question is: Can the flavors of natural foods be reproduced by mixing substances found in food flavor analyses? Yes, some flavors can be reconstructed, hut usually there is only partial resemblance, no matter how pleasant the synthetic flavor may be. Sometimes the analysis for flavor-components does not give the true picture. Some of the natural constitutents may have suffered hydrolysis or oxidation during the isolation process. For example, dimethyl sulfide has been isolated from the volatile components of cooked cabbage, cauliflower, or broccoli. However, it has been shown that the dimethyl sulfide is a decomuosition vroduct of the L-S-methylNone of the compounds had a coffee odor, although furfuryl mereaptan, GH.0-CHBH, which has an obtrusive odor, did resemble the aroma of coffee when highly diluted. Only by recombining over 40 of the compounds could a mixture be obtained whose odor approached that of coffee. The mercaptans are present in the coffee as thioacetals of cmbonyl compounds ($0).
JOURNAL OF CHEMICAL EDUCATION
cysteine sulfoxide present in these foods. Similarly, allylisothiocyanate has been isolated from fresh cabbage, but it is believed to be present in the form of its thioglucoside. On the basis of this flavor-precursor notion, enzymes have been found which can convert flavor-precursors into the natural flavor of the food (4). The enzymes, called flauorese enqmes, are obtained from the fresh food or biologically related foods. When added to a dehydrated food which is rather tasteless, the natural food flavor is restored. Many foods, such as peas, pineapples, carrots, etc., which undergo flavor changes or losses during processing can he made to taste identical with the fresh food. There are two fundamental aspects of the sense of taste to be explored. One object is to discover the molecular properties of a substance which are responsible for its characteristic taste. The other goal is to learn the mechanism by which contact on the tongue is transformed into a nerve impulse to be sensed as taste. We feel things with our fingers but we do not detect a taste from this contact. On the other hand, we can feel things on our tongues which have little or no taste. Hence, there is a unique process at the tongue by which we are able t o taste substances, and substances must have certain molecular properties to have a "taste." Scientists of several disciplin-chemists, physicists, physiologists, psychologists-have been studying the sense of taste for many years. Some scientists focus their investigations on the physiological mechanism of taste perception, others study individual taste preferences and subjective effects on the taste sense, and still others attempt to relate chemical and physical properties of substances t o their tastes. I n order to understand the significance of various experiments and theories on the sense of taste, the physiology of the taste organ will first be described briefly. THE TASTE ORGAN (5) Physiology. Distributed about the tongue are tiny mounds called papillae, each surrounded by a moat (Figure 1). The papillae are of three or four different general shapes but have the same functional architecture. Glands secrete a watery fluid into the
Fig"..
1.
Ps.iU..
and Teats Buds
moat, possibly to flush the moat or to prepare the surface of taste receptors for new stimuli. In the walls of each moat are embedded taste buds. The total number of taste buds decreases with age. I n children, taste buds are found on the tongue, on the insides of the cheeks, and on the epiglottis and larynx. In adults, they are located chiefly on the upper portion VOLUME 35, NO.9, SEPTEMBER, 1958
Figure 2.
Details of.
T-to
Bud
of the tongue and number about 9000. Withim each taste bud are a number of elongated cells which end in filaments protruding out of the taste bud pore (Figure 2). Histochemical studies show the presence of certain enzymes in various parts of the taste organ (6). For example, the following enzymes are some of those found in rabbits: Taste bud cell Hexosediphosphatc~se Acid phosphiltase 3- and 5-Nucleotidase Esterase Adenosine triphosphatase
To& bud pores Hexosediphosphatase Acid phosphatase 3- and 5-Nucleotidase Esterme Glycerophosphatase Adenosine triphasphatase
Taste bud hairs Hexasediphosphatase 3-Nucleotidase Esterase Glycerophasphatase
Taste innervation is very complex. There are three nerve cables serving the tongue, and they intercommunicate through fine branches near their roots, some of which enter the taste buds. These nerve cables contain touch, temperature, and pain fibers as well as taste-sensitive fibers. Hence, it is very difficult to trace taste messages to the brain in man. For this and other reasons, most electrophysiological studies on taste have been with animals (rats, cats, etc.) whose nerve network is much more simple (27). Like all other senses, the tongue soon gets adapted to a given taste upon continued stimulation. The sensory apparatus becomes fatigued, but after a sufficient rest it regains its sensitivity. It has been said jokingly that Wisconsin cheese-tasters are aware of this and take a sip of whiskey after each sample in order to restore the keenness of the tongue.
I
Warning! The reader is reminded that mostof thesubstances mentioned in this article, including salts, are t o x i o and some ertremely so. In the absence of any specific information, all compounds should be regarded as being poisonous. If a trace of solid or a solution is tasted, the mouth should be rinsed afterwards several times before swallowing.
Taste Qualities. I t is generally accepted that there are four basic qualities of taste: sweet, sour, salty, and bitter. The sweet taste is most readily sensed at the tip of the tongue, the bitter taste at the back, the sour taste a t the edge, and the salty taste along the tip and edge (Figure 3). From experience, it is known
Figure 3.
Tho T&a Quality Ra.io".
of the Toncrue
that the sour and salty tastes are stimulated by acids and salts, respectively. Bitter and sweet tastes are found among substances varying widely in structure. Essentially all acids are sour. The common acidic agent in aqueous media is the hydronium ion and although the sourness of solutions increases with acidity of the solution, the variation depends upon the source of hydronium ions. Mineral acids such as sulfuric and hydrochloric cannot be distinguished by taste and their sourness is inversely proportional to the pH of the solution. Organic acids and their anions have distinct tastes and may be more sour than expected from the pH of their solutions (ref. ( 5 ) , p. 296; ref. (9),p. 132 ff). Some acids are both sour and bitter such as picric acid, and some are sour and sweet such as citric acid. The typical salty taste is that of table salt. The tastes of salts depend on the anion and the cation, but not all salts are salty. For illustration:
excepkions. Since all salts do not taste the same, it is obvious that they stimulate receptors other than "salty" receptors. The same conclusion can be reached regarding acids: they stimulate sites other than the "sour" receptor end-organs. Furthermore, the saltiness of sodium chloride, for example, is reduced by sugars or heat, but increased by acids. The bitter taste is found in most magnesium salts, most alkaloids, many amines, and in a variety of organic compounds. Except for the acids, which are usually sour, most organic compounds are either sweet, bitter, or tasteless. The sweet taste is found in a wide variety of organic substances, and in spite of many, many attempts by different investigators, no widely applicable relationship between structure and taste has been found (see following: Physicochemical Studies). Monosodium glutamate ("Accent") has a strong meat flavor and is used to improve the flavor of many types of foods, including meats, seafoods, and most vegetables. It is ineffective on fruits and some dairy products. Solid monosodium glutamate is sweet and salty but dilute solutions have a trace of all four tastes. As one might expect, there are differences in taste sensitivity between species. For example, sodium chloride is much more effective than potassium chloride in producing a stimulation in the rat but potassium chloride is the more effective in the cat and rabbit. Furthermore, differences exist within any one species. This is very obvious from the wide variation in our individual taste ~references.~It is very strikingly illustrated with phenylthiocarbamide, called PTC. H
s Phenylthioearbamide ("PTC")
To 10%-30% of the population, PTC is tasteless, whereas 70%-90% find it extremely hitter (81).4 This dual taste is found in many but not all compounds
I
having an -NH-C=S group in their structures (7). Other substances such as creatine, mannose, and sodium benzoate also divide people on the basis of their taste responses, but the classifications are not confined just to two group^.^
S"lf",
LiCl NaCl NHKl KC1 RhCl
IiBr NaBr N&Br
LiI NaI
KBr
NHJ
RhBr C8Br
XI RhI
NaNO. KNOI Na.SO,
Sally and bitter
Bitter CrCl
MgSOa
CsI Sweet
Lead acetate Beryllium acetate
A strict relationship between the taste and properties of these salts is obscure. There is a trend from salty to bitter taste with increasing molecular weight, and there is a trend in effectiveness of taste stimulation with ionic mobilities, although in each sequence there are
a This is just one of the many individual differences that the "normal" person exhibits as discussed by Roger J. Williams, past president of the American Chemical Society (26). A certain Malayan youth was able to discriminate a 6.5 X 10-8M PTC solution from water, whereas two Malayan women could not taste even a solution 218 times stronger ($3). I t bas been reported (82) that a. "taster" can taste PTC when i t is dissolved in his own saliva, hut not when in a "nantaster's" saliva, and not on his dry tongue. 'An interesting ramification of this was attempted by A. L. Fox of Colgate-Pahnolive. Sodium benzoate which is sweet, sour, bitter, salty, or tasteless, depending on the individual, divides each of the PTC groups into five subgroups. Ten classifications are possible, but Fox found 76% of 1000 subjects examined to fall into four of the combinations. Then Fox tested several food preferences of these four groups and found a certain resemblance in their likes and dislikes. On this basis, Fox suggested that when a new food or beverage is brought out for sampling, it should be tested on people belonging to these four msjor taste-groups. However, see the apposing view of E. F. Hoover of Wise Potato Chip (SO).
JOURNAL OF CHEMICAL EDUCATION
El'leetrophysiologica1 Studies (8, 27). The use of electronic equipment makes it possible t o record and amplify nerve impulses in nerve fibers at points between the receptor cells and the brain. The complexity of the human nerve network has restricted most of these studies to animals such as cats, rats, dogs, hamsters, and guinea pigs. The general picture is that a gustatory stimulation acts upon the receptor filament or cell, producing changes a t or within the cell membrane. A nerve fiber is a very poor electrical conductor when conducting as a copper wire conducts. Yet, it can transmit a small current a t the rate of 1-100 meters per second. This is possible only if energy is available for propagation and is released point by point as the impulse proceeds. Nerve cells act like tiny batteries, with a potential difference across the cell membrane. One theory proposes that a taste stimulus brings about a depolarization of the nerve fiber ending. This local depolarization then affects
the adjacent region of the nerve fiher and thereby a wave of depolarization changes moves along the nerve fiber. Each nerve sectio'n recharges after 0.5 to 2 milliseconds, ready to transmit another impulse. These impulses may be recorded, and are called "spikes" on an oscillograph record. A certain level of electrical activity is always observed when the receptor cell is "at rest", which is fairly constant in a given nerve fiher. Taste stimulation of the receptor site produces a change in frequency and amplitude of nerve impulses. An integrated record can be made for a quantitative measure of receptor stimulation. The bioelectric potential is due to an ion concentration difference on the two sides of the semipermeable cell wall. The concentration of sodium ions is much higher in the fluid outside than inside the nerve fiber, and the reverse is true for potassium ions. A sudden increase in sodium permeability through the cell wall allows sodium ions to pass through and this quickly depolarizes the cell.
PHYSICOCHEMICAL STUDIES
But,
Structure-Taste Correlations. Many many attempts have been made to account for the tastes of substances in terms of their chemical structures. Several limited correlat,ions have been reported (9) but no rigid, widely applicable theory has evolved. For example, generalizations such as the following have been-found: (1) Polyhydroxy and polyhalogenated aliphatics are usually sweet, e.g., glycerol, sugars, and chloroform. (2) Upon ascending a homologus series, taste usually disappears along with water solubility. (3) Free bases are usually bitter, particularly alkaloids. (4) Some aldehydes but rarely ketones are sweet. (5) Symmetry often leads to bitterness or destroys the sweet taste:
Very hitter
I I H,C20 OC2Hr Tasteless
(6) Introduction of a phenyl group frequently makes sweet compounds become bitter or tasteless, e.g. :
i, Very sweet
But,
CH-CHOH-CHIOH CH8-CHOH-CHOH-CH.OH HOCH-CHOH--CH20H H-CONH-CH, (C2HEhN-CONH,
Bitter C6Hh-CHOH-CHZOH CsHiCHOH-CHOH-CH&H CsHj-OCH-CHOH-CHIOH H-CONH-C6H5 (CnHAN-CON(C&h
Methyl glucoside
Phenylglucoside and hen~ylglucoaide
Sweet
Bitterish
Weakly bitter
Bitter
(GCSH,,)XN, /N(C6Hwi)z C I1
6 Bitter
306X6 6 X = Sucrose as a standard = 1.
VOLUME 35, NO. 9, SEPTEMBER, 1958
On the other hand, there are exceptions to each of these generalizations, and often the introduction of a given functional group into diffefent structures produces opposite effects on their tastes. This has made it difficult t o discern any invariant structure-taste relationships (9, 26). A few examples can be given here (pp. 440-41.)
Not all sugars are aweet and even momers may have widely different tastes: H
OH
Inmeases sweetness NHCONH, NHCONHt
d
H
\ /
Introductionof alkoxylgroup:
I
1
\ /
C-7
I
H-A-OH
I
HO-C-H
I
H-C4-
91X
I
I
~
Bitter
H-C-OH
H-LoH
H , O ~ H ~ O H Isomaltose, sweet
Not Sweet
Sweet
(6-a-~-Glueopyran08,~l-o-
glucose)
I
0"".
Destroys sweetness
HO-LH
CpHsO/' \SO,/ Not Sweet
3061
H-C-OH
I
COOH
H-bOJ
cH3-o-A L20H Gentiobiose, bitter (6-#-D-Glucopymnosyl-Dglorose)
Sweetish
Methylation:
Bitter
Methylation: Produces sweetness NHCONHl NHCONH*
CHs Sweet
Bitter
HzN-CONH? Bitter HzN-(CHd-COOH Not sweet
Destroys sveetness NHCONH, NHCONH.
~C~H: Not sweet
HzN-CON(CHJn Sweet
Sweet CsHnNHSOsNa "Sucmyl" 33.8X
CHsNH-(CH2)a-COOH Sweetish
Not sweet CeH,,NCHaS08Na Not sweet
Introduction of OH groups: Inweases sweetness CH, CH,OH AH?
CHoH I 1
Deweases sweetness
Vinylags: Are m e t
CHJ I
cH90H I
OCas
OCsHr
Are not sweet OC2H5 OC&
0 $ 3$ \NHCONHl
H
I NO2
bH
AH
1
NHCONH. Sweet
I
NHCONHt Sweeter
I
NHCONHz 91Xe
NHCONHI
