Endogenous inhibitors, accumulation

Changes in binding can occur in many situations. In some diseases, the concentrations of binding proteins may be altered, and accumulation of endogenous inhibitors of binding may occur. For example, in renal... 

P. Vallance, A. Leone, A. Calver, J. Collier and S. Moncada, Accumulation of an Endogenous Inhibitor of Nitric Oxide Synthesis in Chronic Renal Failure, Lancet 337 (1992) 572-757. 

Vallance, P., Leone, A., Calver, A., Collier, J., and Moncada, S. (1992). Accumulation of endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 339, 575. 

Feedback inhibition of amino acid transporters by amino acids synthesized by the cells might be responsible for the well known fact that blocking protein synthesis by cycloheximide in Saccharomyces cerevisiae inhibits the uptake of most amino acids [56]. Indeed, under these conditions, endogenous amino acids continue to accumulate. This situation, which precludes studying amino acid transport in yeast in the presence of inhibitors of protein synthesis, is very different from that observed in bacteria, where amino acid uptake is commonly measured in the presence of chloramphenicol in order to isolate the uptake process from further metabolism of accumulated substances. In yeast, when nitrogen starvation rather than cycloheximide is used to block protein synthesis, this leads to very high uptake activity. This fact supports the feedback inhibition interpretation of the observed cycloheximide effect. 

Kriedemann e t al. (69) have proposed that endogenous PA functions as an inhibitor of photosynthesis following relief of water stress when this metabolite accumulates. This proposal was based on the observation that plant extracts containing PA strongly inhibited photosynthesis in detached leaves of several species (69). However, subsequent work with crystallized PA has shown that it was not PA that inhibited photosynthesis, but rather impurities that were present in the solvents used (76). Thus, the physiological role of PA, if any, remains to be determined. 

Early reports suggested that methoprene exerted its toxic effect not as a JH mimic but as an inhibitor of JH degradation, resulting in the accumulation of endogenous JH (Slade and Wilkinson, 1973). More recent studies involving insect tissue culture or cell culture have eliminated this hypothesis. 

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