Magnesium and manganese have proved physically and functionally interchangeable in many isolated biological systems investigated in vitro. This lack of discrimination contrasts sharply with the high biological specificity exhibited by intact mammals under a large variety of conditions. The dichotomy between intact animals and their isolated systems might be due at least partially to presence vs. absence of an intact circulation. Hence the capability of mammalian plasma to discriminate between the alkaline earth and the transition metal was investigated by means of equilibrium dialysis, exchange, ultrafiltration, ultracentrifugation, and zone eleetrophoresis. The states of the respective elements are thus contrasted as follows: (a) Magnesium is partially bound, manganese totally. (b) Magnesium is nonselectively bound by serum proteins, manganese selectively by a fix-globulin. (c) Under conditions approaching physiological, the two metals do not interchange. This is interpreted as indieating that the plasma proteins contribute to biological specificity by discriminating between a trace metal and a macronutrient.
I N T R O D U C T I O NMagnesium and manganese are physically and functionally interchangeable in m a n y isolated biological systems studied in vitro. This interchangeability has been found in studies of antibiotic effects (1); of enzymatic activities (2-4); of metal deficiency (5, 6); of oxidative phosphorylation (7, 9); of fatty acid synthesis (8); of metal transport (10); and of mutagenic effects (11). It was even proposed that such results could be expected from the similar eomplexing tendencies and crystal chemistry of these metals (12)(13)(14). Yet, a striking biological specificity characterizes these metals in mammalian organisms, as exemplified by the entirely different consequences of manganese vs. magnesium deficiency (15). These differences suggest that the trace amounts of tissue manganese exert essential functions in the presence of the comparatively large concentrations of magnesium. Indeed, in one mammal, manganese-mag-
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