Taste bitter compounds: structure

Sweet and Bitter Compounds Structure and Taste Relationship... 

BeUtz, H.-D., Chen, W., Jugel H., Treleano, R., Wieser, H., Gasteiger, J., Marsili, M. Sweet and bitter compounds Structure and taste relationship, in Food taste chemistry (Ed. Boudreau, J.C.), ACS Symposium Series 115, p. 93, American Chemical Society Washington, D.C. 1979... 

Just as a multiplicity of hydroxyl groups is normally related to sweetness, multiple nitro groups and the sulfur atom in the —S—S— or —C=S— linkage have been associated with bitter taste. Thus, it was obseiwed that a compound containing three nitro groups, such as picric acid, is usually bitter, and that those with two nitro group may be bitter. Compounds having structure A are also frequently bitter, and it was deduced that the bitterness of the acyl-thiocarbamide class of compounds is due to structure B. 

The sweet taste and olfactory responses to a variety of stimuli are examples of chemical senses that utilize protein receptors for initial detection of the stimulus. Most bitter compounds have a hydrophobic component which enables their direct interaction with the cell membrane however, some evidence suggests a protein receptor mechanism. The cooling sensation is treated as a chemesthetic sense, where stimulation takes place at the basal membrane. However, compounds that evoke this response have very specific structural limitations, and most are related to menthol. For purposes of discussion, bitter and cooling sensations will be discussed under generalized receptor mechanisms. 

Sweetness Production by the Combination of Bitter and Sweet Tastes. Sensory tests using typically bitter compounds such as brucine, strychnine, phenylfiiiourea, caffeine and bitter peptides were performed. Sensory tests using typically bitter compounds such as brucine, strychnine, phenylthiourea, caffeine and bitter peptides were performed. Sensory taste impression were also measured for combinations of acetic acid (sour) and typical bitter compounds (5). The data from these studies indicated that the tastes of ese bitter/sour mixtures changed to a sweet taste regardless of their chemical structure of the bitter component (Table II). 

Bitter compounds are also formed in solutions of alanine with xylose and rham-nose.284 Twenty-six HPLC fractions were obtained, seven of which were shown to have high impact on taste dilution analysis. Structures 37-41 accounted for 57% of overall bitterness. The compounds have low threshold values introduction of methyl groups into the furyl rings increase the threshold value. On the contrary, substituting the furyl ring-0 by S (42) lowered the threshold value to almost 104 times lower than that of caffeine on a molar basis. 

Sweet taste is produced by a wide variety of compounds. SHAL-LENBERGER and ACREE (6) regard an acid/base system (AH/B-System) as the shared structural element. This system must satisfy certain steric conditions and can interact with a complementary system of a receptor via 2 hydrogen bonds (Fig. 1). KIER (7) expanded this model by assuming an additional interaction witfi an apolar group X in a suitable position (Fig. 1). Both models are applicable to compounds with great variations in structure. There are no similar comprehensive concepts for bitter compounds which can also occur in the most varying chemical classes. 

Now, I feel I have dwelt too long on the subject of "umami , but the word "umami" in Japanese language sometimes means "sweetness". As to the sweeteners, it is no wonder that such a great deal of work has been done on new sweeteners of natural and artificial origin. Until now, such work has been a kind of hit and miss business. Therefore, the last half of the day was devoted to understanding some of the structural features of molecules that determine their taste properties. Based on the advanced stereo-chemical studies on a large number of sweet and bitter compounds by Dr. Ariyoshi, Dr. Belitz and Dr. Ney, our understanding of the molecular properties of certain taste compounds has advanced markedly. 

Structural analogy with alkaloid compounds. One of these compounds, named quinizolate (13), exhibits an intense bitter taste at an extraordinarily low detection threshold of0.00025 mmol/kg of water. This novel taste compound was found to have 2000- and 28-fold lower threshold concentrations than the standard bitter compounds caffeine and quinine hydrochloride, respectively, and, therefore, it is claimed to be one of the most intensely bitter compounds reported so far [46]. It is important to note that in sensory evaluation there is a difference between detection threshold and recognition threshold the first determines the concentration of a substance that makes one able to say this is not pure water the second means that the panelist is able to state this is bitter. Therefore these reported data on the taste of new compounds must to be taken carefully especially in comparison with others. 

The same conclusions were also recorded for vertebrate herbivores. For example rabbits (Cuniculus europaeus) and hares (Lepus europaeus) clearly prefer the sweet plants and leave the bitter plants almost untouched, at least as long as there is an alternative food source. In conclusion, although taste perception in mammals and insects differs in many aspects, there also some similarities both in anatomy and in the function of the bitter taste perception. A comparison of the effects of alkaloids, as well as of other bitter compounds, will be assisted by further advances in the knowledge of the structure of taste genes and receptors. 

BeUtz H-D, Wieser H. Bitter compounds occurrence and structure-activity relationship. Food Reviews International 1985 1 271-354. Meyerhof W. Elucidation of mammalian bitter taste. Rev Physiol Biochem Pharmacol 2005 154 37-72. 

The simplest tastant, the hydrogen ion, is perceived as sour. Other simple ions, particularly sodium ion, are perceived as salty. The taste called umami is evoked by the amino acid glutamate, often encountered as the flavor enhancer monosodium glutamate (MSG). In contrast, tastants perceived as bitter or sweet are extremely diverse. Many bitter compounds are alkaloids or other plant products of which many are toxic. However, they do not have any common structural elements or other common properties. Carbohydrates such as glucose and sucrose are perceived as sweet, as are other compounds including some simple peptide derivatives, such as aspartame, and even some proteins. 

Caffeine belongs to a large class of compounds known as alkaloids. These are of plant origin, contain basic nitrogen, often have a bitter taste and complex structure, and usually have physiological activity. Their... 

Fig. 3 Structural diversity of bitter compounds. The chemical structures of absinthin, aristolochic acid, denatonium, strychnine, D-(-)-salicin, and phenylthiocarbamate (PTC) are depicted. Note the different sizes, charges, and three-dimensional architectures of these compounds that all activate at least one of the human bitter taste receptors...

Table 1 shows the taste profile obtained for crude cheese, reconstituted cheese made vnth homogenized proteins, fat with and without WSE, and WSE. Their comparison allowed the impact of each fiaction on the taste of the cheese to be evaluated. The omission of WSE led to a tasteless product, showing that WSE contained all the taste-active compounds. In reconstituted cheese where the structure of die matrix was almost totally degraded, bitterness was weaker and saltiness higher than in crude cheese (Table 2). The omission of fat and proteins from the reconstituted cheese caused an increase of saltiness and a decrease of bitterness compared to crude cheese. These data demonstrated that, in the crude cheese, the matrix structure partially masked the saltiness and increased the bitterness due to taste-active compounds. In addition, the comparison with results obtained with grated cheese in which the destructuring was intermediate between crude and reconstructed cheese for the same taste descriptors (Table 2) confirmed that the more die matrix was destructured, the more the bitterness increased and die saltiness decreased. Thus, cheese taste might be explained by the taste of die WSE containing the taste-active compounds modulated by the masking effect of both fat and proteins but also by an effect linked to the cheese mafrbc structure.

True alkaloids derive from amino acid and they share a heterocyclic ring with nitrogen. These alkaloids are highly reactive substances with biological activity even in low doses. All true alkaloids have a bitter taste and appear as a white solid, with the exception of nicotine which has a brown liquid. True alkaloids form water-soluble salts. Moreover, most of them are well-defined crystalline substances which unite with acids to form salts. True alkaloids may occur in plants (1) in the free state, (2) as salts and (3) as N-oxides. These alkaloids occur in a limited number of species and families, and are those compounds in which decarboxylated amino acids are condensed with a non-nitrogenous structural moiety. The primary precursors of true alkaloids are such amino acids as L-ornithine, L-lysine, L-phenylalanine/L-tyrosine, L-tryptophan and L-histidine . Examples of true alkaloids include such biologically active alkaloids as cocaine, quinine, dopamine, morphine and usambarensine (Figure 4). A fuller list of examples appears in Table 1. 

Many bixxer compounds contain both hydrophobic and hydrophilic sites which can alter cell membranes through penetration. There is a correlation between bitter intensity and hydrophobicity-solubility indexes such as fee octanol/water partition coefficient, lo (7). Penetration may directly affect cAMP phosphodiesterase as part of fee transduction process (see below). A bitter receptor protein may be involved wife certain bitters, such as specific structural requirements wife fee bitter tasting dipeptides and denatonium salts (27). The latter is used in some consumer products to avoid accidental ingestion. A receptor mechanism is also supported by fee existence of a genetic "taste blindness" for some bitter materials (see below). 

FIGURE 3. Chemical structures of compounds exhibiting bitter taste. 

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