Effect of sparsomycin in vivo and in vitro on hepatic polyribosomes and protein synthesis

Abstract

Sparsomycin (20 μg/20 g of body wt), when administered intraperitoneally to mice, induced marked disaggregation of hepatic polyribosomes and inhibited incorporation of [ 14C]leucine into hepatic proteins by 90 per cent. However, addition of Sparsomycin in vitro to a cell-free amino acid incorporating system did not cause disaggregation of polyribosomes, yet inhibited the incorporation of [ 14C]leucine into proteins by 80 per cent. In studies concerned with initiation of protein synthesis, it was observed that Sparsomycin inhibited the factor-dependent initiation of new polyphenylalanine chains, as well as factor-dependent binding of either phe- tRNA or met- tRNA to 40S ribosomal subunits. These findings are interpreted as suggesting that, in vivo, Sparsomycin disaggregates polyribosomes probably by interfering with the initiation process.