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Biomedical subjects

W Gevers

Publications and source records attributed to W Gevers.

At least 91 records · Page 5Linked to original sources
PubMed1973

Cell-free protein synthesis in heart and skeletal muscles from polymyopathic hamsters.

1. Cell-free protein synthesis was studied in striated and smooth muscles in an attempt to elucidate the primary genetic defect in polymyopathic hamsters. 2. When washed membrane-free polyribosomes from myopathic and control heart muscle were individually recombined with pH5 enzymes from both types of animals, the pH5 enzymes from myopathic muscle were less active in polypeptide synthesis than those from controls, irrespective of the source of polyribosomes. 3. The same defect was present in skeletal-muscle preparations. 4. Both the initial rate and the maximum extent of incorporation were affected in the defective preparations from myopathic muscle. 5. Concentration differences, with respect to total protein and RNA, were not responsible. 6. Preincubation of the pH5 enzymes resulted in a greater degree of inhibition. 7. The defect in the pH5 enzymes from myopathic muscle was also expressed in poly(U)-directed polyphenylalanine synthesis. 8. Acid proteinase activity in extracts of control and myopathic muscle was the same but general ribonuclease activity in the latter extracts was higher. 9. The defect was also present when both types of pH5 enzymes were prepared in the presence of the ribonuclease-asborbent bentonite. 10. pH5 enzymes from uterine smooth muscle, brains and livers of myopathic animals were similarly affected in homologous and heterologous combinations. 11. It is concluded that the general tissue defect is both qualitative and quantitative in nature, implying that there is a shortage of some essential soluble component in the pH5 fraction which is accompanied by the presence of an altered substituent. This prevents the attainment of extents of polypeptide synthesis in vitro obtained in control extracts from unaffected animals.

Amino Acyl-tRNA Synthetases↗
PubMed1973

Evidence for defective transfer ribonucleic acid in polymyopathic hamsters and its inhibitory effect on protein synthesis.

1. Different reaction steps involved in protein synthesis were studied in skeletal muscles from control and myopathic hamsters. 2. There was no difference between partially purified aminoacyl-tRNA synthetases from myopathic and control animals in yield or catalytic activity, as tested with exogenous deacylated tRNA. 3. However, isolated deacylated tRNA from myopathic muscle was aminoacylated by these synthetases to a lesser extent than that derived from control muscle. 4. Addition of deacylated tRNA isolated from control muscle improved the performance of pH5 enzymes from myopathic muscle in polypeptide synthesis on homologous polyribosomes; tRNA isolated from myopathic animals did not. 5. Preparation of extracts from both types of animals in the presence of the ribonuclease-absorbent bentonite led to an increased capacity of endogenous tRNA to accept amino acids in pH5 enzymes prepared from normal and abnormal tissue, but the difference between the two systems remained the same. 6. Total tRNA nucleotidyltransferase activity, tested with twice-pyrophosphorolysed rat liver tRNA, was identical in both extracts. 7. Added tRNA nucleotidyltransferase incorporated more AMP and CMP into endogenous tRNA with the pH5 enzyme from myopathic muscle than with that from control muscle. 8. Preincubation of deacylated tRNA from myopathic muscle with ATP, CTP and tRNA nucleotidyltransferase more than doubled its subsequent aminoacyl-acceptor activity, and halved the extent of the defect relative to aminoacylation of control tRNA similarly treated. Endogenous tRNA in pH5 enzyme preparations behaved likewise. 9. It is suggested that a 3'-exonuclease in myopathic muscles attacks tRNA molecules in such a way that some of them remain substrates for tRNA nucleotidyltransferase, which may incorporate into RNA not only AMP and CMP, but also GMP. 10. Cell-free protein synthesis in preparations from myopathic hamster muscles is limited by the supply of intact tRNA molecules.

Adenosine Triphosphate↗
PubMed1973

Evidence for the binding of the carcinogen 3-methylcholanthrene to both the purine and the pyrimidine bases of hamster fibroblast deoxyribonucleic acid.

The binding of [(3)H]3-methylcholanthrene to the DNA of hamster fibroblasts was studied by using chemical methods for DNA degradation. DNA depurinated by mild acid hydrolysis released approximately half of the radioactivity at the same rate as the purine bases, but the resulting apurinic acid still contained radioactive carcinogen.

Animals↗
PubMed1969

Interrelation between activation and polymerization in gramicidin S biosynthesis.

The nucleic acid-independent biosynthesis of the peptide antibiotic gramicidin S results from the interaction of an enzyme bearing phenylalanine in activated form with a polyenzyme system charged with the other four component amino acids. After reaction with ATP, magnesium, and any or all of its amino acid substrates, the polyenzyme system (mol wt 280,000) yields complexes containing AMP and the respective amino acids in the proportion of 1 to 2. Similar complexes are formed by another enzyme (mol wt 100,000) on incubation with ATP, magnesium, and L- or D-phenylalanine. The amino acids are probably bound as aminoacyl adenylates and then transferred to another function on the enzyme. Initiation of polymerization is achieved by combination of the two complexes. No ATP is needed for completion of synthesis, and free intermediates are not released. Enzyme organization and specificity are responsible for the ordering of the amino acid sequence.

Adenosine Triphosphate↗
PubMed1969

Peptidyl transfers in gramicidin S bisoynthesis from enzyme-bound thioester intermediates.

The biosynthesis of the peptide antibiotic gramicidin S involves successive peptidyl transfer reactions between intermediates bound in thioester linkages to two active enzyme fractions, I and II. Fraction II activates and recemizes phenylalanine, and then initiates peptidyl transfer by catalyzing a reaction between the carboxyl group of D-phenylalanine, bound to an enzymic sulfhydryl group, and the free imino group of L-proline, one of four L-amino acids all linked by their carboxyl functions to separate sulfhydryl groups on fraction I. Successive reactions of this type in the active centers of the multienzyme complex of fraction I lead to the formation of thioester-bonded nascent peptide chains and, ultimately, of the antibiotic product.

Amino Acid Sequence↗