Abstract
The effect of concentration of some chelating agents on proline hydroxylation and the synthesis of collagenous and non‐collagenous proteins was studied in skin slices of chick embryo. In a group of eight chelating agents a good correlation was found between the degree of inhibition of hydroxylation and the stability constant of ferrous chelates. No correlation with the stability of cupric complexes was found. The failure of 2,9‐dimethyl‐1,10‐phenanthroline to inhibit hydroxylation also suggests participation of Fe2+. The study of the influence of different times of preincubation of the tissue with chelating agents showed that 2,2′‐dipyridyl and 1,10‐phenanthroline inhibit the hydroxylation of proline already within 10 minutes. In addition 2,2′‐dipyridyl and in 1 mM concentration also inhibits after 2 hours of action the incoporation of [14C]proline into collagenous proteins and does not change during a 4 hour incubation the synthesis of non‐collagenous proteins. Phenanthroline, in the same concentration, inhibits already during the first 60 minutes of incubation both the synthesis of collagen as well as of non‐collagenous proteins. Chelating agents which do not penetrate cell membrane are without effect on the reactions studied.The blockade of hydroxylation is a specific result of the chelation of bivalent iron. Chelating agents influence more easily the incorporation of amino acids into collagenous proteins than synthesis of globular proteins. This effect is considered specific because it is related to the chelating properties of the substances investigated. All other investigated substances without chelating properties inhibit, according to the concentration used, synthesis of both types of protein equally, so that the decrease in hydroxyproline formation is secondary to the inhibition of proline incorporation. Close correlation between the inhibition of protein synthesis and general toxicity of these substances has been found.
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