Anti Metabolite Theory


  • Orhan Canbolat gazi medical school


Inhibition of the key element controlling the metabolic process would decrease or completely inhibit the synthesis of the intracellular key molecules. The broad field called antimetabolites originated from this magnificent simple rationale. While Wood’s works on antibacterial antimetabolites were going on, Hitchings found that cells such as bacterial, tumoral or protozoal cells that grew and proliferated rapidly required large amount of nucleic acids. In particular, the prevention of synthesis by changing the substrates of key enzymes of nucleotide or nucleic acidmetabolism, and the information obtained by the introduction of synthetic nucleotide analogs into DNA and RNA synthesis has improved our knowledge in this field. The expansion of our knowledge regarding the metabolism of key enzymes controlling the nucleotide metabolism can provide us with new perspectives in treatment of diseases with cancer and viral diseases in the first place. After all, enzymes, which are complex protein structures control all the chemical reactions including those related to nucleic acid. While studies carried out starting from the beginning of the century on enzymes targeting the nucleotide metabolism had found a valuable place thanks to the antimetabolite theory, the number of groups working on the structural characteristics and kinetics of enzymes in particular have started to decrease gradually. The major challenges in this area are that enzyme kinetics studies are largely dependent on instrument infrastructure, are labor intensive, and the results of the study are not satisfactory when applied to technology. In addition to the lack of popularity of such studies, long working periods, difficulties in publishing and citing studies limit the field. Enzyme kinetics is currently the most challenging multidisciplinary field in biochemistry. The limitations mentioned above discouraged the scientists working in this field and the field started to shrink. Despite all the difficulties, we must continue the work necessary to understand the structural features and behavior of this "working class" that controls the metabolism of nucleotides and nucleic acids. It can be predicted that the antimetabolite theory will come to the fore again in the treatment of viral diseases that emerge as an important health problem and in the treatment of many important diseases, especially cancer. The purpose of this article is to shed light on the field again.






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