Characteristics of the interaction between 2-alkylmalonates and the substrate-binding site of the dicarboxylate carrier of rat liver mitochondria

The effect of thirteen synthetic 2-n-alkyl derivatives of malonic acid on the rate of the mitochondrial succinate oxidase reaction controlled by the dicarboxylate carrier, was studied. These compounds were shown to act as competitive inhibitors of succinate transport and could interact with the carrier according to the 1:1 stoichiometry. The affinity of the inhibitor for the carrier increased in parallel with the increase in the alkyl residue length. This dependence was impaired only in the case of pentyl-, hexyl- and heptylmalonates having close values of inhibition constants. The data obtained suggest that the polar site and two hydrophobic regions are located in the vicinity of the carrier active site. The possible organization of the carrier substrate-binding site is discussed.     

The role of T-system immunity in reparatory regeneration of the bone tissue in animals

It has been demonstrated in experiments on mice (CBA X C57BL) X F1, thymectomized and irradiated by 800 R, with the haemopoietic system restored by bone marrow (B-mice) that in these animals, as compared with the controls, the changes in cellular immunity (inhibition of natural killer cells and stimulation of individual functions of the phagocytizing cells) are accompanied by considerable inhibition of osteogenesis. Compensatory regeneration of broken thigh-bone in B-mice is delayed by 5--10 days in various elements of the regenerated tissue in comparison with normal mice. Anatomical formation of the provisional callus in B-mice is not completed on day 21 and approaches a 14-day regenerate of the controls. The obtained results suggest the participation of T-system immunity in the reparatory regeneration of bone tissue.     

Reduced Amino Acid Specificity of Mammalian Tyrosyl-tRNA Synthetase Is Associated with Elevated Mistranslation of Tyr Codons

Quality control operates at different steps in translation to limit errors to approximately one mistranslated codon per 10,000 codons during mRNA-directed protein synthesis. Recent studies have suggested that error rates may actually vary considerably during translation under different growth conditions. Here we examined the misincorporation of Phe at Tyr codons during synthesis of a recombinant antibody produced in tyrosine-limited Chinese hamster ovary (CHO) cells. Tyr to Phe replacements were previously found to occur throughout the antibody at a rate of up to 0.7% irrespective of the identity or context of the Tyr codon translated. Despite this comparatively high mistranslation rate, no significant change in cellular viability was observed. Monitoring of Phe and Tyr levels revealed that changes in error rates correlated with changes in amino acid pools, suggesting that mischarging of tRNA^Tyr with noncognate Phe by tyrosyl-tRNA synthetase was responsible for mistranslation. Steady-state kinetic analyses of CHO cytoplasmic tyrosyl-tRNA synthetase revealed a 25-fold lower specificity for Tyr over Phe as compared with previously characterized bacterial enzymes, consistent with the observed increase in translation error rates during tyrosine limitation. Functional comparisons of mammalian and bacterial tyrosyl-tRNA synthetase revealed key differences at residues responsible for amino acid recognition, highlighting differences in evolutionary constraints for translation quality control.     

Effects of an epiphyseal peptide preparation epithalamin on serotonin metabolism in the pineal gland of rats]

5-day morning injections to pubertal male rats of polypeptide epithalamin preparation obtained from cattle epiphysis, in dose of 0.25 mg/100 g body mass induced the increase of serotonin epiphyseal concentration night peak, N-acetylserotonin and melatonin and didn't produce any essential influence on 5-methoxytryptamine, 5-oxy- and 5-methoxyindoleacetic acid level. It has been concluded, that epiphyseal peptides and indoles interact according to ultrashort connection, epiphyseal peptides point of application is the reaction of tryptophan transformation into serotonin and its further metabolism in N-acetylserotonin and melatonin. It has been suggested that the increase of epiphyseal melatonin production is on the basis of epithalamin therapeutic action.     

Age-related characteristics of the effects of epithalamin on serotonin metabolism in the pineal gland of rats]

The biosynthesis of serotonin into melatonin was decreased in old (18-20-month) in comparison to young (4-5-month) male Wistar rats. 5-day morning injections to young and old rats with polypeptide pineal preparation (epithalamin) in a dose of 2.5 mg/kg of body weight induced the increase in the night peak of serotonin, N-acetylserotonin and melatonin in young and melatonin alone in old rats and did not influence 5-methoxytryptamine, 5-oxy- and 5-methoxyindoleacetic acids level. These data support suggestion of ultrashort loop between pineal peptides and indoles and that epithalamin increases the metabolism of serotonin into melatonin.