GTP degradation to guanine catalyzed by ribosomal subunits and microsomal-wash factors.
Ribosomes from stringent strains of bacteria generate (p)ppGpp if incubated with uncharged tRNA, a ribosomal wash fraction, GTP and ATP. By contrast, an analogous system from rat liver does not transform GTP to (p)ppGpp but degrades it to guanine. The reaction requires the ribosomal subunits, a 40 000-Mr and a 60 000-Mr microsomal wash protein factor and is inhibited if the ribosomal A-site is charged with aminoacyl tRNA. The degradation of GTP to guanine occurs in the following four distinct reaction steps: (a) hydrolysis of GTP to GDP plus Pi, (b) hydrolysis of GDP to GMP plus Pi, (c) hydrolysis of GMP to guanosine plus Pi, (d) hydrolysis of guanosine to guanine plus ribose. The reaction step (a) is inhibited by fusidic acid, cycloheximide, emetine, tetracycline and puromycin. The hydrolysis of GDP is inhibited strongly by fusidic acid, emetine and tetracycline. A putative physiological significance of this ribosome-dependent pathway in the processes of growth control of animal cells under conditions of amino acid deprivation is discussed.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D006147:Guanine / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism; D006151:Guanosine / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D006150:Guanine Nucleotides; D006151:Guanosine; D006147:Guanine; D006160:Guanosine Triphosphate; D005033:Ethylmaleimide