Suppression of the biosynthesis of guanosine triphosphate by protein synthesis inhibitors

Journal Article · Fri Oct 10 04:00:00 EDT 1980 · J. Biol. Chem.; (United States)

OSTI ID:6795656

Volkin, E; Boling, M E; Jones, M H; Lee, W H; Pike, L M

In a prior report it was observed that CTP synthesis and concomitant incorporation of CMP into RNA and dCMP into DNA were markedly reduced in cells cultured in the presence of cycloheximide and puromycin. Experiments described here with Novikoff hepatoma cells reveal that the purine biosynthetic pathway is similarly affected. When the cells are subjected to cycloheximide (30 or 60 ..mu..g/ml) or puromycin (100 ..mu..g/ml), there is a substantial reduction in the bioconversion of hypoxanthine, adenosine, and deoxyadenosine into guanylate compared to untreated cultures. Whereas synthesis (counts per min/nmol) of pool ATP was 70 to 100% of controls, that of pool GTP was 20 to 35% of controls. Incorporation of AMP into RNA was 40 to 60% of controls, but that of GMP was only 10 to 25% of controls. Incorporation of dAMP into DNA averaged 10% of controls, but that of dGMP was only 4% of controls. Synthesis of guanylates from formate by the de novo pathway was similarly reduced, but incorporation of guanosine, which enters via kinase action alone, was not disproportionately lowered. These results suggest that protein synthesis inhibitors cause a severely reduced availability of newly synthesized GTP and CTP as well as their deoxy counterparts, dGTP and dCTP, the proximal precursors for the synthesis of RNA and DNA. However, the nanomolar levels of all nucleoside triphosphates remain high, probably as a result of recycling of nucleic acid breakdown products. Thus, reduced synthesis of these compounds may restrict nucleic acid synthesis only of some sort of compartmentation leads to a limitation of these precursors at the site(s) of nucleic acid synthesis.

• Research Organization: Oak Ridge National Lab., TN
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 6795656
• Journal Information: J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 255:19; ISSN JBCHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADENOSINE
AMINES
AMP
ANIMAL CELLS
ANTIBIOTICS
ATP
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
BIOSYNTHESIS
CARBON 14 COMPOUNDS
CELL CULTURES
CYCLOHEXIMIDE
CYTOSINE
DATA
DNA
DRUGS
EXPERIMENTAL DATA
FUNGICIDES
GUANOSINE
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
HYPOXANTHINE
INFORMATION
INHIBITION
LABELLED COMPOUNDS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXYGEN COMPOUNDS
PESTICIDES
PHOSPHATES
PHOSPHORUS COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PRECURSOR
PROTEINS
PURINES
PUROMYCIN
PYRIMIDINES
RIBOSIDES
RNA
SYNTHESIS
TRITIUM COMPOUNDS
TUMOR CELLS