Céline E. Riera and Johannes le Coutre

1. Introduction

Until recently, it was commonly accepted that taste perception consisted of five distinct taste modalities: sweet, sour, bitter, salty and umami (the savoury taste of monosodium glutamate). However, the possible existence of extra taste sensations which do not fall into these five recognised categories is now being discussed. In the exciting quest to understand the molecular pathways of taste sensations, recent findings indicate the possibility for mechanisms to sense mineral nutrients for salts of zinc, iron, copper, magnesium and calcium (Riera et al. 2009; Tordoff et al. 2008). The researchers showed that minerals not only make partial use of sweet, bitter and umami transduction pathways but they also target sensory neurons responsible for pungency and heat sensations. Taken together, the findings illustrate the complexity of a metallic sensory transduction pathway, rationalising the ability to regulate the uptake of dietary mineral salts via direct oral perception.

2. Gustatory and somatosensory systems

2.1 Gustatory perception

The hedonic value of nutrients is evaluated in the mouth by our chemical senses, most notably the gustatory and somatosensory systems, which work in concert to detect compounds in the mouth. Gustatory information is processed by taste buds contained in the tongue papillae. Taste is composed of five basic modalities with hedonically positive (pleasant) and negative (unpleasant) attributes: sweet, bitter, sour, salty and umami. Among the pleasant perceptions, sweet taste allows for identification of energy-rich nutrients such as sugars; umami permits the detection of amino acids; and salty taste guarantees the proper dietary electrolyte balance. Bitter and sour tastes prevent the ingestion of poisonous substances and are more associated with unpleasant sensations.

Taste sensations are transduced at the taste cell level by unique and discrete pathways. Taste buds contain four types of morphologically different cells, type I, II, III and IV (Roper, 1989). It is believed that in the assignment of function to a cell type, the sweet, umami and bitter transduction machinery is found in one subtype of cells (type II). Signal transduction underlying these modalities is initiated by the binding of the tastant to the taste G-protein coupled receptor (GPCR). Sweet stimuli are detected by the T1R2 and T1R3 heterodimer composed of two members of the T1R family (Li et al. 2002; Zhao et al. 2003; Damak et al. 2003). As for umami transduction, T1R1 and T1R3 have been shown to dimerise and form an amino acid receptor (Nelson et al. 2002; Nelson et al. 2002). Finally, the taste receptors 2 (T2Rs) family was identified as a group of receptors for bitter tasting chemicals (Adler et al. 2000; Chandrashekar et al. 2000; Matsunami et al. 2000).

After tastant binding to the GPCR, the receptor will activate gustducin, a heteromeric G protein (McLaughlin et al. 1992), leading to the release of Gβγ subunits (Zhang et al. 2003; Huang et al. 1999) and the subsequent stimulation of phospholipase Cβ2 (PLCβ2; Zhang et al. 2003; Huang et al. 1999; Rossler et al. 1998). PLCβ2 hydrolyses phosphatidylinositol-4,5-biphosphate (PIP2) to produce the two intracellular messengers inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), which ultimately leads to the opening of transient receptor potential (TRP) protein TRPM5 (Zhang et al. 2003; Perez et al. 2002) and subsequent propagation of the signal to gustatory afferent nerves.

2.2 Somatosensory perception

Somatosensory stimulation by temperature, painful stimuli and irritation in the mouth is mediated by the lingual branch of the trigeminal nerve projecting to the brainstem trigeminal ganglion. The related perception is initiated at the level of primary afferent neurons that terminate as free nerve endings embedded in the oral mucosa. The fibres are responsible for pungent sensations evoked by culinary spices such as capsaicin, the molecule contained in red hot chilli pepper that gives spicy foods their characteristic hot sensation.

Over the past years, several temperature sensitive TRP channels expressed in sensory neurons have been identified as detectors of temperature and noxious chemical stimuli. Among them, TRPV1 was the first mammalian Transient Receptor Potential Vanilloid (TRPV) identified and is activated by capsaicin. In addition, TRPV1 is activated by heat (≥43°C; Caterina et al. 1997) and many other chemicals, which include the pungent compounds present in black pepper (piperine; McNamara et al. 2005) and garlic (allicin; Macpherson et al. 2005).

3. Metallic taste: a dynamic interplay between gustatory and somatosensory cues

3.1 Concentration dependence

Recently, we characterised cell types expressing GPCRs and TRP channels that are directly involved in mineral sensory detection. Each metal salt (Fe²⁺, Zn²⁺, Mg²⁺ and Cu²⁺) activates specific molecular targets, which can change depending upon concentration. Using taste preference assays in mice deficient for selected taste receptors, we could show that wild type mice displayed strong preference for low concentrations of Fe²⁺ and Zn²⁺ through a TRPM5 containing a signalling transduction cascade. Moreover, suppression of T1R3, the receptor for sweet and umami stimuli in taste cells leads to indifference in the mice, suggesting that these metals induce pleasantness possibly through one of these pathways. This is consistent with psychophysical data describing that low concentrations of these salts could produce a ‘umami-like’ taste.

At high concentrations, all metals (Fe²⁺, Zn²⁺, Mg²⁺ and Cu²⁺) produce robust aversive responses that are mediated partially through TRPM5 and TRPV1 dependent mechanisms, explaining some of the well known bitter and aversive sensations for these salts. 

3.2 Mineral salts target several subpopulations of cells within the taste bud

The transduction of mineral taste alters the organisation of taste transduction pathways involving TRPM5 and T1R3, initially believed to be co-expressed and encoding preference. It appears that if T1R3 and TRPM5 work in concert to detect pleasant sensations of Fe²⁺ and Zn²⁺, T1R3 behaves as an aversive detector for Mg²⁺ and Ca²⁺. Low concentrations of Mg²⁺ and Ca²⁺ are tasteless to mice but the suppression of T1R3 in mice renders these nutrients attractive (Tordoff et al. 2008).

The dual role of T1R3 can be understood in a scenario where different subpopulations of taste cells expressing T1R3 co-exist in the taste bud. Some T1R3-expressing cells, where TRPM5 is a downstream signalling molecule, appear to be connected to areas of the brain underlying preference, whereas other T1R3-containing cells project to fibres coding for aversion. One open question remains to understand whether T1R3 is an integrator of a broader range of metallic modalities or if it is responsible only for a unique metallic taste quality. Also, to convey aversion, this receptor may have several other partners than T1R1 or T1R2. Future research on T1R3 will provide a better understanding of metallic taste.

4. Metallic taste may participate in regulating mineral intake

The ability of an organism to distinguish energy-rich nutrients from poisonous substances is critical for survival. Minerals are essential for many of the body's cellular processes and keep them running efficiently. Minerals are also necessary in the structural composition of body tissues and various biological processes. Humans need a wide range of minerals to maintain good health: mineral depletion or excess may cause devastating effects on the body. In particular, it is well documented that high concentrations of minerals have toxic properties, causing gastro-intestinal malaise (Wang and Borison 1951; REISSMAN et al. 1955; Barceloux 1999; Makale and King 1992). Therefore, the ability to taste minerals is consistent with a taste-driven mechanism to prevent poisoning as indicated by the aversion of wild-type mice to high amounts of iron, zinc, copper and magnesium. Yet another open question is to find out whether humans can consciously regulate their mineral intake by orienting their food choice to a high or low mineral diet.

5. Conclusions

A key feature of taste perception resides in its transduction at the taste cell level by unique pathways. In contrast, the compounds that produce metallic taste stimulate several gustatory and somatosensory transduction pathways. The recent findings on mineral taste detection highlight a bivalent role for T1R3 that may be independent of sweet and umami signalling, which requires further attention. Understanding the perception of metals will help to develop food supplements with better nutritional profiles.

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