Biomaterial Database

The effect of ethanol on polypeptide chain initiation in reticulocyte lysates. Inhibition of recycling of initiation factor eIF-2. 1988

S Cox, and C G Proud

Biological Laboratory, University of Kent, Canterbury, U.K.

Using the reticulocyte cell-free system, we have investigated the mechanism by which ethanol inhibits the initiation of protein synthesis. Ethanol inhibited the formation of 40S-initiation complexes, and this effect correlated well with the inhibition by ethanol of overall peptide-chain initiation. Ethanol was a more potent inhibitor of translation at 37 degrees than at 30 degrees. The inhibition of peptide-chain initiation and 40S-initiation complex formation in reticulocyte lysates under other conditions is associated with increased phosphorylation of the alpha-subunit of protein synthesis initiation factor-2 (eIF-2 alpha) and the inhibition of recycling of this factor. Recycling of eIF-2 is mediated by another protein factor GEF (= guanine nucleotide-exchange factor). The addition of ethanol to reticulocyte lysates led to increased phosphorylation of eIF-2 alpha and to a decrease in the rate of exchange of guanine nucleotides bound to eIF-2. This second finding indicated that recycling of eIF-2 was impaired probably due to decreased availability of GEF. Using purified components it was found that ethanol inhibited the ability of GEF to stimulate eIF-2 and that this inhibition showed a similar temperature dependence to the effect of ethanol on overall protein synthesis. Taken together, these results suggest that ethanol leads to inhibition of peptide-chain initiation both through increased phosphorylation of eIF-2 alpha and by directly inhibiting the productive interaction of eIF-2 and GEF.

UI	MeSH Term	Description	Entries
D008274	Magnesium	A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
D010442	Peptide Chain Initiation, Translational	A process of GENETIC TRANSLATION whereby the formation of a peptide chain is started. It includes assembly of the RIBOSOME components, the MESSENGER RNA coding for the polypeptide to be made, INITIATOR TRNA, and PEPTIDE INITIATION FACTORS; and placement of the first amino acid in the peptide chain. The details and components of this process are unique for prokaryotic protein biosynthesis and eukaryotic protein biosynthesis.	Chain Initiation, Peptide, Translational,Protein Biosynthesis Initiation,Protein Chain Initiation, Translational,Protein Translation Initiation,Translation Initiation, Genetic,Translation Initiation, Protein,Translational Initiation, Protein,Translational Peptide Chain Initiation,Biosynthesis Initiation, Protein,Genetic Translation Initiation,Initiation, Genetic Translation,Initiation, Protein Biosynthesis,Initiation, Protein Translation,Initiation, Protein Translational,Protein Translational Initiation
D010448	Peptide Initiation Factors	Protein factors uniquely required during the initiation phase of protein synthesis in GENETIC TRANSLATION.	Initiation Factors,Initiation Factor,Factors, Peptide Initiation,Initiation Factors, Peptide
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D011494	Protein Kinases	A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.	Protein Kinase,Kinase, Protein,Kinases, Protein
D011506	Proteins	Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.	Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D012156	Reticulocytes	Immature ERYTHROCYTES. In humans, these are ERYTHROID CELLS that have just undergone extrusion of their CELL NUCLEUS. They still contain some organelles that gradually decrease in number as the cells mature. RIBOSOMES are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic "reticulum" (not the same as the ENDOPLASMIC RETICULUM), hence the name reticulocytes.	Reticulocyte
D000431	Ethanol	A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.	Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D015852	Eukaryotic Initiation Factor-2	Eukaryotic initiation factor of protein synthesis. In higher eukaryotes the factor consists of three subunits: alpha, beta, and gamma. As initiation proceeds, eIF-2 forms a ternary complex with Met-tRNAi and GTP.	EIF-2,Peptide Initiation Factor EIF-2,EIF-2 alpha,EIF-2 beta,EIF-2 gamma,EIF-2alpha,EIF-2beta,EIF-2gamma,EIF2,Eukaryotic Initiation Factor-2, alpha Subunit,Eukaryotic Initiation Factor-2, beta Subunit,Eukaryotic Initiation Factor-2, gamma Subunit,Eukaryotic Peptide Initiation Factor-2,EIF 2,EIF 2 alpha,EIF 2 beta,EIF 2 gamma,EIF 2alpha,EIF 2beta,EIF 2gamma,Eukaryotic Initiation Factor 2,Eukaryotic Initiation Factor 2, alpha Subunit,Eukaryotic Initiation Factor 2, beta Subunit,Eukaryotic Initiation Factor 2, gamma Subunit,Eukaryotic Peptide Initiation Factor 2,Initiation Factor-2, Eukaryotic,Peptide Initiation Factor EIF 2
D019892	eIF-2 Kinase	A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.	Protein Kinase PKR,Protein Kinase, RNA Activated,RNA-Dependent Protein Kinase,p68 Kinase,DAI Protein Kinase,DSRNA-Dep Protein Kinase,Double Stranded RNA-Dependent Kinase (dsl),Double Stranded RNA-Dependent eIF-2 alpha Protein Kinase,Eukaryotic Initiation Factor 2alpha Kinase,Heme Controlled Repressor,Heme-Controlled Inhibitor,Heme-Controlled Translational Repressor,Heme-Regulated eIF-2alpha Kinase,Hemin Controlled Repressor,Hemin-Controlled Translational Repressor,P68 Protein Kinase,Self-Phosphorylating Protein Kinase,TIK Kinase,dsRNA-Activated Inhibitor,eIF-2alpha Kinase,eRF, eIF-2 Recycling Factor,p65 Kinase,Controlled Repressor, Heme,Controlled Repressor, Hemin,DSRNA Dep Protein Kinase,Double Stranded RNA Dependent eIF 2 alpha Protein Kinase,Heme Controlled Inhibitor,Heme Controlled Translational Repressor,Heme Regulated eIF 2alpha Kinase,Hemin Controlled Translational Repressor,Inhibitor, Heme-Controlled,Inhibitor, dsRNA-Activated,Kinase PKR, Protein,Kinase, DAI Protein,Kinase, DSRNA-Dep Protein,Kinase, Heme-Regulated eIF-2alpha,Kinase, P68 Protein,Kinase, RNA-Dependent Protein,Kinase, Self-Phosphorylating Protein,Kinase, TIK,Kinase, eIF-2,Kinase, eIF-2alpha,Kinase, p65,Kinase, p68,PKR, Protein Kinase,Protein Kinase, DAI,Protein Kinase, DSRNA-Dep,Protein Kinase, P68,Protein Kinase, RNA-Dependent,Protein Kinase, Self-Phosphorylating,RNA Dependent Protein Kinase,Repressor, Heme Controlled,Repressor, Heme-Controlled Translational,Repressor, Hemin Controlled,Repressor, Hemin-Controlled Translational,Self Phosphorylating Protein Kinase,Translational Repressor, Heme-Controlled,Translational Repressor, Hemin-Controlled,dsRNA Activated Inhibitor,eIF 2 Kinase,eIF 2alpha Kinase,eIF-2alpha Kinase, Heme-Regulated,eRF, eIF 2 Recycling Factor