The High Specificity of the Manganese Pathway Through the Body12

The accepted ideas about the physiological role of manganese have been derived predominantly from in vitro experiments.However, these are characterized by lack of specificity: Only a limited discrimination between manganese and some other metals is shown, for instance, in metal transport systems (1, 2), in enzyme activation (2-4) and in the preservation of mitochondria (5).The conclusions from these experiments were of in- terest because they threw new doubt on the func- tional specificity and even on the essentiality of manganese in the living organism.Thus it be- came necessary to ascertain whether manganese may be replaced in the intact animal as well.To investigate this, we have used a variation of the classical technique of flooding the organism with metals which we were led to believe would sub- stitute for manganese.Surprisingly, these kindred metals were ineffective in eluting radiomanganese from the body: Only manganese compounds proved effective in that regard.The results suggest that there exists a segment in the pathway of manganese through the body, the properties of which permit the passage of that metal only.This paper deals with the implications of this finding both in reference to manganese as well as to the elements which have been thought not to possess such an in vivo specificity. MATERIALS AND METHODS Experiments with intact animalsAnimals.These were seven week old Swiss albino male mice, weighing 16 to 18 grams.They were housed in cages, the bedding of which consisted of shredded corn cobs.When dietary restrictions were imposed, 'This work was supported by the United States Atomic Energy Commission.It was accorded an Honorable Men- tion in the A.