Effect of pyrophosphate and orotidine monophosphate on cytosine deaminase regulatory properties

Summary The maximal velocity of the reaction (V_max) and the half-saturation constant (K_0.5) values of theS. typhimurium cytosine deaminase were altered in the presence of its effectors, pyrophosphate and orotidine monophosphate. From the kinetics of orotidine monophosphate inhibition of cytosine deaminase, it was characterized as a mixed-type noncompetitive inhibitor.     

Activity of orotate metabolizing enzyme complex and various urea-cycle enzymes in mutant mice with ornithine transcarbamylase deficiency

Summary The overall activity of the enzyme complex consisting of orotate phosphoribosyl transferase and orotidine monophosphate decarboxylase, and of various enzymes of the urea cycle, has been studied in sparse-fur (spf) mutant mice with ornithine transcarbamylase deficiency. The enzyme complex has a lower overall activity, which could be caused by disturbed pyrimidine metabolism due to hyperammonemia. Other enzymes of the urea cycle do not show any significant change.Acknowledgments. The research was supported by a grant from the Conseil des Clubs Sociaux and Fondation Justine Lacoste Beaubien, Montréal. The authors wish to thank Ms Louise Poulin and Ms Francine Poisson for technical assistance.     

AID in antibody perfection

Expressed immunoglobulin (Ig) genes undergo alterations in sequence and genomic structure in order to optimize antibody function. A single B cell-specific factor, activation-induced deaminase (AID), initiates these changes by deamination of cytosine to uracil. Uracil in DNA is encountered commonly, and conserved pathways are responsible for its faithful repair. However, at the Ig loci of B cells, AID-initiated damage is processed to produce three distinct outcomes: somatic hypermutation, class switch recombination and gene conversion. This review focuses on the role of AID in Ig gene diversification, emphasizing how AID functions within the mechanism of the Ig gene diversification pathway; and highlights open questions for future research, particularly the most provocative current question: what makes a gene a target for AID-initiated mutagenesis?     

Changes in activity levels of AMP deaminase and adenosine deaminase in the Indian apple snail,Pila globosa (Swainson) during starvation and aestivation stress

Summary Activity levels of AMP deaminase and adenosine deaminase have been studied in hepatopancreas, foot and mantle tissues ofPila globosa with reference to starvation and aestivation. The activity levels of both enzymes were decreased in all the tissues of aestivating snails while in starved animals AMP deaminase activity was increased, in contrast to the decreased adenosine deaminase activity.Acknowledgments. K. Srinivasa Moorthy and B. Kasi Reddy are thankful to the Department of Science and Technology, New Delhi for the financial assistance. Reprint requests should be addressed to C.S.C.     

Brain cyclic nucleotide and energy metabolite responses to subanesthetic and anesthetic concentrations of halothane

Adult rats were exposed to 0.5, 1.0 and 1.5% halothane, delivered in air, for 1 h. Whole brain 3',5'-cyclic adenosine monophosphate (cAMP) of halothane-exposed rats showed only a slight increase relative to control values. 3',5'-Cyclic guanosine monophosphate (cGMP) was increased significantly in halothane-exposed rats, and the response was directly related to the halothane concentrations. Adenosine triphosphate (ATP) and phosphocreatine (PC) remained unchanged relative to control values. Correspondence of these values to apparent discrepancies in the literature is discussed.     

Histochemical demonstration of differences in AMP deaminase activity in rat skeletal muscle-fibres

The histochemical method for AMP deaminase confirms that rat slow-twitch fibres contain less AMP deaminase activity than fast-twitch fibres. However, the enzyme appears similarly localized in all fibre types.     

Histochemical demonstration of differences in AMP deaminase activity in rat skeletal muscle-fibres

Summary The histochemical method for AMP deaminase confirms that rat slow-twitch fibres contain less AMP deaminase activity than fast-twitch fibres. However, the enzyme appears similarly localized in all fibre types.This study was supported by NIH grant AM 21617.     

AMP deaminase, 5'-nucleotidase and adenosine deaminase in rat myocardial tissue in myocardial infarction and hypothermia

AMP deaminase, 5'-nucleotidase and adenosine deaminase have been estimated in skeletal muscle and myocardial tissue in normal rats and in rats subjected to experimental myocardial infarction or hypothermia. A difference in the enzyme distribution was found between the right and left ventricles in the normal rat. A decrease in the activity of 5'-nucleotidase and an increase in the activity of adenosine deaminase were observed in infarcted myocardial tissue. The activity of all 3 enzymes was found to be depressed in the myocardium in rats subjected to hypothermia. These results are discussed in relation to adenosine production and its beneficial effects.     

Human adenosine deaminase and chromosome 20

Summary In patients exhibiting in marrow cells deletion of the long arm of chromosome 20, the specific activities of adenosine deaminase in cells of the peripheral blood are normal. This suggests that the gene for adenosine deaminase is not localized to the distal segment of the long arm of this chromosome.This work was supported by Grants from the National Health and Medical Research Council of Australia and the Anti-Cancer Council of Victoria.     

AMP deaminase, 5′-nucleotidase and adenosine deaminase in rat myocardial tissue in myocardial infarction and hypothermia

Summary AMP deaminase, 5-nucleotidase and adenosine deaminase have been estimated in skeletal muscle and myocardial tissue in normal rats and in rats subjected to experimental myocardial infarction or hypothermia. A difference in the enzyme distribution was found between the right and left ventricles in the normal rat. A decrease in the activity of 5-nucleotidase and an increase in the activity of adenosine deaminase were observed in infarcted myocardial tissue. The activity of all 3 enzymes was found to be depressed in the myocardium in rats subjected to hypothermia. These results are discussed in relation to adenosine production and its beneficial effects.     

Occurrence of sepiapterin deaminase in the normal type silkworm,Bombyx mori

Summary Sepiapterin deaminase was prepared from the normal strain of the silkworm, Bombyx mori. After inhibition experiments, this enzyme was found to have the same properties as that isolated from the lemon mutant strain. Several new inhibitors and their K₁ values are described for the deaminase.The authors wish to thank Dr Wm. Gyure, Cape Cod Hospital, Hyannis, Massachusetts, USA, for his help in preparing this report.     

Effect of prostaglandin E1 on rat gastric motility and cyclic nucleotide content.

Administration of exogenous prostaglandin E1 resulted in an increase in contractility of rat fundic muscle measured in vivo; a significant decrease in fundic tissue levels of cyclic- adenosine monophosphate and a significant increase in cyclic-guanosine monophosphate.     

Nitroglycerin-induced desensitization of vascular smooth muscle may be mediated through cyclic GMP-disinhibition of phosphatidylinositol hydrolysis

Summary The purpose of this study was to investigate the hypothesis that nitroglycerin-induced desensitization of vascular smooth muscle is mediated through cyclic GMP-disinhibition of phosphatidylinositol hydrolysis. Norepinephrine-induced contraction and increased levels of inositol monophosphate, a measure of phosphatidylinositol hydrolysis, in rat aorta. Prior treatment with nitroglycerin inhibited both the norepinephrine-induced contraction and the elevated levels of inositol monophosphate to the same relative magnitude. The nitroglycerin-induced inhibition of contraction and inositol monophosphate formation were prevented in tissues desensitized with nitroglycerin. These results suggest that: 1) nitroglycerin may inhibit vascular smooth muscle contraction through cyclic GMP-inhibition of phosphatidylinositol hydrolysis and 2) desensitization to the relaxant effects of nitroglycerin may be due to disinhibition of the hydrolysis.Acknowledgments. This work was supported by grants from the Veterans Administration, American Heart Association Southwestern Ohio Chapter, and BRSG 507 RR05-408-24 and RO1 HL 34895 from the National Institutes of Health to RMR. JKC is a recipient of a Key Pharmaceutical Company Predoctoral Fellowship. Address all correspondence to R. M. Rapoport.     

Effect of prostaglandin E1 on rat gastric motility and cyclic nucleotide content

Summary Administration of exogenous prostaglandin E₁ resulted in an increase in contractility of rat fundic muscle measured in vivo; a significant decrease in fundic tissue levels of cyclic-adenosine monophosphate and a significant increase in cyclic-guanosine monophosphate.     

Nitroglycerin-induced desensitization of vascular smooth muscle may be mediated through cyclic GMP-disinhibition of phosphatidylinositol hydrolysis

The purpose of this study was to investigate the hypothesis that nitroglycerin-induced desensitization of vascular smooth muscle is mediated through cyclic GMP-disinhibition of phosphatidylinositol hydrolysis. Norepinephrine-induced contraction and increased levels of inositol monophosphate, a measure of phosphatidylinositol hydrolysis, in rat aorta. Prior treatment with nitroglycerin inhibited both the norepinephrine-induced contraction and the elevated levels of inositol monophosphate to the same relative magnitude. The nitroglycerin-induced inhibition of contraction and inositol monophosphate formation were prevented in tissues desensitized with nitroglycerin. These results suggest that: nitroglycerin may inhibit vascular smooth muscle contraction through cyclic GMP-inhibition of phosphatidylinositol hydrolysis and desensitization to the relaxant effects of nitroglycerin may be due to disinhibition of the hydrolysis.     

Effect of dibutyryl cAMP and theophylline on cultured rat embryonic shields.

Effects of N6, O2 dibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP) and theophylline (Th) on cultured rat embryonic shields were studied. After addition of db-cAMP to the culture medium, an increase of the weight of explants and of the incidence of the skeletal muscle was observed. Theophylline seems to be ineffective.     

Adrenocorticotrophic hormone and cyclic adenosine monophosphate effect on mouse adrenal cortical cell membrane potential

Adrenocorticotrophic hormone (ACTH) and cyclic adenosine monophosphate (cAMP) both caused a rapid and transient depolarization of the resulting membrane potential of superfused rat adrenal cortical cells. The membrane depolarization to both secretagogues were very similar. The membrane potential changes occurred as early as 0.1 min and were dose dependent in both onset and extent of depolarization.     

A study on the pharmacokinetics in mouse of adenine-9-beta-D-arabinofuranoside 5-monophosphate conjugated with lactosaminated albumin

In plasma of mice injected with adenine-9-beta-D-arabinofuranoside monophosphate (ara-AMP) coupled to human lactosaminated serum albumin (L-HSA) some of the ara-AMP molecules are enzymatically released, whereas others remain linked to L-HSA. Evidence has been obtained that ara-AMP is not deaminated when it is conjugated to L-HSA, in contrast to the free drug which is rapidly metabolized to its hypoxanthine derivative.     

Zum protonentransfer in modellsystemen für die komplementäre Basenpaarung in Nukleinsäuren

Summary By means of IR-spectroscopy, proton transfer processes of base-pairing models of deoxyribonucleic acid (1:1 mixed crystals of 9-methyl adenine and 1-methyl thymine and of 9-ethyl guanine and 1-methyl cytosine) in measurable quantities can be excluded at temperatures between –150 and +30°C.     

Adenosine deaminase activity in peripheral blood cells from SJL/J mice

Summary Adenosine deaminase (ADA) activities were measured in peripheral blood cells of SJL/J mice, and compared with those of C57BL/6J animals. No association was observed between the levels of lymphocyte or erythrocyte ADA and immunologic abnormalities in SJL/J mice nor was evidence obtained to suggest a relationship between ADA activity and tumorigenesis in this strain.This work was supported in part by a University College Faculty Research Grant.