For many years, the nature of alkaloids in biology was a mystery. It has been difficult to understand the function of these compounds in plant metabolism. There are many explanations for why plants, animals and micro-organisms produce alkaloids.
Nowadays, when genomes, DNA and genes serve as the basis for biological explanations, this issue is of great importance and still open for discussion and for deep scientific analysis. Despite the advanced research in the field, a final comprehensive biological explanation of the nature of alkaloids is still on the way. In this sense the alkaloid mystery continues to exist. New compounds are being discovered all the time; however, their biological significance remains unexplained. The slow pace of science and scientific research requires a lot of time to arrive at such explanations. Moreover, the structures of many of these compounds are unexpected and their bioactivity is surprising. The molecular mechanisms and metabolic roles of newly discovered compounds have remained unclear. Alkaloids from marine environments and those produced by microorganisms and animal skin are, in particular, objects of current chemical and biological research. Moreover, the nature and role of alkaloids has been based on a throng of theoretical hypotheses compiled during the last 200 years. It has even been hypothesized that alkaloids are plant wastes and an end product of metabolism322. Today, the role of alkaloids can be explained by two factors: the functions of these compounds inside and outside the organism producing them. The external function of alkaloids is presently a particularly strong and growing research area323,324,325,326. This trend in alkaloid research is based on the hypothesis that alkaloids are compounds that solely play a protective role in interaction with other organisms (as some kind of organic bio-weapons). This seems to be a rather limited oversimplification of the issue. Although there is strong evidence of this kind of activity, it is not entirely clear if it is a basic function of these compounds in the organisms producing them. The idea that this ecologically important role may only be a secondary function and that alkaloids primarily function in connection with the regulation of metabolism as the result of gene expression should not be dismissed. It is known that in the case of quinolizidine alkaloids the total removal of these compounds by genetic means leads to the death of the lupine plant327. This suggests that alkaloids are compounds fundamental for cell activity and gene code realization in the genotype328. This also means that alkaloids basically function in connection with genes, enzymes and proteins inside the organism. Moreover, it is also known that quinolizidine alkaloids are able to change their structural chemical configurations under changing cellular pH conditions. This observation and experimentally measured effect first noted in the 1990s has unfortunately been given little literary attention by other scientists. Although this self-regulation process is still not understood in detail, there are many recent studies which prove that chemical structural changes influence large changes in the biological activity of chemical compounds54,213,329,330.
Alkaloids are non-toxic in vacuoles where they are stored but toxic when they escape from the vacuoles. They have to change their chemical configurations and biological activity in different cells and tissues according to pH changes. This means that some alkaloids can have different biological activity in different cell
conditions and different receptors. This process has to be genetically regulated (Figure 77). Future detailed studies will likely clear up this fascinating and complex matter concerning the biological nature of alkaloids.
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