Zinc is an essential metallotransmitter

In biochemistry textbooks, amino acids that are derived from the diet are classified as essential amino acids. However, metals such as zinc that are derived from the diet are described as trace elements. Even though gaseous molecules are termed as gasotransmitters, the term 'metallotransmitter' for zinc is found in only one current peer-reviewed publication. Describing metals as trace elements instead of metallotransmitters may impede the investigation, validation, or refutation of the gasocrine signaling theory I recently proposed. Likewise, for any organisms whose normal functioning is dependent on metallotransmitters that they do not synthesize, such metallotransmitters must be considered as essential metallotransmitters for those organisms. I propose that the term ‘metalloreceptor’ for proteins whose structures can be altered upon the interaction with metallotransmitter, resulting in downstream cellular signaling events. An instance of metallotransmitter-metalloreceptor interaction is the documented zinc ions-GTF3A/TFIIIA interaction, causing structural and functional alterations in the protein. I propose that transcription factor GTF3A/TFIIIA is one such zinc metalloreceptor in vertebrates. In mammals, metalloreceptors are likely a variety of metal ion-binding proteins expressed in nearly every cell exposed to metals, as opposed to specific zinc-sensing receptors such as GPR39. For instance, a gasoreceptor for Nitric oxide (NO) is the enzyme soluble guanylyl cyclase, while the androgen receptor is a transcription factor. Likewise, metalloreceptors are also likely to be of different protein classes with diverse functions. Acknowledging the complexity of metallotransmitter-metalloreceptor interactions will facilitate a systematic search for metalloreceptors for all metallotransmitters. It will also allow exploration of the inter-competition between metallotransmitter-metalloreceptor bindings, exemplified by the case of lithium vs. magnesium, and the mechanisms by which proteins achieve metal-specific binding and/or activities. In addition, it will enable to integrate the role of interaction of gasotransmitters with metallotransmitters and its impact on gasocrine signaling. Differences in experimental outcomes between labs may be also attributed to variations in metallotransmitter concentrations. Accepting Zinc as an essential metallotransmitter will require revisions in biology text books.