Nucleotide metabolism

The RBC contains certain enzymes of nucleotide metabolism (eg, adenosine deaminase, pyrimidine nucleotidase, and adenylyl kinase) deficiencies of these enzymes are involved in some cases of hemolytic anemia. 

Chromosomal mutations in E. coli result in overproduction of dihydrofolate reductase (DHFR). Higher concentrations of trimethoprim, which may not be therapeutically achievable, are therefore required to inhibit nucleotide metabolism. Other mutations lower the affinity of DHFR for trimethoprim. These two mechanisms of resistance may coexist in a single strain, effectively increasing the level of resistance to the antibiotic. 

Nicotinate and pyridine nucleotide metabolism in Escherichia coli and Saccharomyces cerevisiae (Unkefer and London 1984)... 

Miyamoto, K. and French, S.W. (1988). Hepatic adenosine nucleotide metabolism measured in vim in rats fed ethanol and a high fat-low protein diet. Hepatology 8, 53-60. 

Deficiencies of enzymes involved in glycolysis, the hexose monophosphate pathway, the closely related glutathione metabolism and synthesis, and nucleotide metabolism have emerged as causes of hereditary nonspherocytic hemolytic anemias (Table 1) (F10, Fll, M27). Some enzyme deficiencies, such as diphospho-glycerate mutase deficiency, lactate dehydrogenase deficiency, and NADH cy-... 

Cyclic nucleotide metabolism cyclic nucleotide Phosphodiesterase Adenylyl cyclase... 

Volume LI. Purine and Pyrimidine Nucleotide Metabolism Edited by Patricia A. Hoffee and Mary Ellen Jones... 

D7. Dietrich, L. S., Friedland, I. M., and Kaplan, L. A., Pyridine nucleotide metabolism mechanism of action of the niacin antagonist, 6-amino-nicotinamide. ]. Biol. Chem. 233, 964-968 (1958). 

Sterol biosynthesis Bile acid biosynthesis C2rSteroid hormone metabolism Androgen and estrogen metabolism Nucleotide Metabolism Purine metabolism Pyrimidine metabolism Nucleotide sugar metabolism Amino sugar metabolism Amino Acid Metabolism Glutamate metabolism Alanine and aspartate metabolism Glycine, serine, and threonine metabolism... 

Folates Yeast, liver, fresh green vegetables Nucleotide metabolism... 

Bi2 (cobalamin) Meat, fish, poultry, milk and milk products produced also by bacteria in the large intestine Nucleotide metabolism... 

Box 20.2 Deficiencies or low activities of enzymes involved in purine nucleotide metabolism... 

These three compounds exert many similar effects in nucleotide metabolism of chicks and rats [167]. They cause an increase of the liver RNA content and of the nucleotide content of the acid-soluble fraction in chicks [168], as well as an increase in rate of turnover of these polynucleotide structures [169,170]. Further experiments in chicks indicate that orotic acid, vitamin B12 and methionine exert a certain action on the activity of liver deoxyribonuclease, but have no effect on ribonuclease. Their effect is believed to be on the biosynthetic process rather than on catabolism [171]. Both orotic acid and vitamin Bu increase the levels of dihydrofolate reductase (EC 1.5.1.4), formyltetrahydrofolate synthetase and serine hydroxymethyl transferase in the chicken liver when added in diet. It is believed that orotic acid may act directly on the enzymes involved in the synthesis and interconversion of one-carbon folic acid derivatives [172]. The protein incorporation of serine, but not of leucine or methionine, is increased in the presence of either orotic acid or vitamin B12 [173]. In addition, these two compounds also exert a similar effect on the increased formate incorporation into the RNA of liver cell fractions in chicks [174—176]. It is therefore postulated that there may be a common role of orotic acid and vitamin Bj2 at the level of the transcription process in m-RNA biosynthesis [174—176]. 

Tetrahydrofolic acid then functions as a carrier of one-carbon groups for amino acid and nucleotide metabolism. The basic ring system is able to transfer methyl, methylene, methenyl, or formyl groups, and it utilizes slightly different reagents as appropriate. These are shown here for convenience, we have left out the benzoic acid-glutamic acid portion of the structure. These compounds are all interrelated, but we are not going to delve any deeper into the actual biochemical relationships. 

Severe combined immunodeficiency arises from inhibition of lymphocyte proliferation because B and T cells are particularly sensitive to allosteric inhibition of which of the following enzymes of purine nucleotide metabolism ... 

The answer is D. Impaired immune function in severe combined immunodeficiency (SCID) is the direct result of blocked DNA synthesis due to inadequate supplies of de-oxyribonucleotides in B and T cells. This effect arises by dATP-induced allosteric inhibition of ribonucleotide reductase, which catalyzes reduction of the 2 -hydroxyl groups on ADP and GDP to form dADP and dCDP. The ultimate cause of many cases of SCID is adenosine deaminase deficiency, which leads to accumulation of dATP and consequent inhibition of ribonucleotide reductase. Although the other enzymes mentioned are also involved in purine nucleotide metabolism, their deficiencies do not lead to SCID. 

Kaneider, N.C., Mosheimer, B., Reinisch, N., Patsch, J.R., and Wiedermann, C.J., Inhibition of thrombin-induced signaling by resveratrol and quercetin effects on adenosine nucleotide metabolism in endothelial cells and platelet-neutrophil interactions, Thromb. Res., 114, 185, 2004. 

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