Rate-limiting steps for protein synthesis in isolated rat liver cells. Role of aspartate availability.
Amino-oxyacetate (carboxymethoxylamine) was found to inhibit protein labelling in isolated liver cells. A similar degree of inhibition (about 70%) was observed of basal and substrate-stimulated rates of protein labelling, ruling out an action on the cellular energy state. Its effect does not seem to be related either to a perturbation of the reduction state of the NAD system or to rate changes in the gluconeogenic pathway. The following observations indicate that amino-oxyacetate inhibits protein labelling by limiting aspartate supply. Amino-oxyacetate was ineffective in a postmitochondrial supernatant under non-limiting amino acid supply conditions. The aspartate cellular content decreases in the presence of amino-oxyacetate, although most other amino acids tend to accumulate. L-Cycloserine was unable to decrease aspartate content and was ineffective in decreasing protein labelling. The inhibitory action of amino-oxyacetate was specifically reversed by incubating cells with amino acids that increase the cellular content of aspartate.
D000596:Amino Acids / Q000494:pharmacology; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002469:Cell Separation; D003523:Cycloserine / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D014176:Protein Biosynthesis; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D007773:Lactates; D011773:Pyruvates; D000625:Aminooxyacetic Acid; D001224:Aspartic Acid; D019344:Lactic Acid; D019289:Pyruvic Acid; D003523:Cycloserine; D005947:Glucose