| Feedback control of ribonucleotide reductase maintains similar amounts of all four deoxynucleotides
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| The reduction of the 2'-hydroxyl of ribose uses a pair of protein-bound sulfhydryls (cysteine residues). The hydroxyl group is released as water, and the cysteines are oxidized to cystine during the reaction. To regenerate an active enzyme, the disulfide must be reduced back to the original sulfhydryl pair by disulfide exchange; this is accomplished by reaction with a small protein, thioredoxin (see Fig. 29.6). Thioredoxin, a highly conserved Fe-S protein, is in turn reduced by the flavoprotein, thioredoxin reductase. The dNTPs are produced by phosphorylation of the dNDPs, using ATP as the phosphate donor.
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| MEASUREMENT OF SERUM URIC ACID CONCENTRATION |
| Hyperuricemia is seen under a variety of conditions characterized by increased cell turnover, e.g. severe infection and inflammation. Diabetic ketoacidosis and renal failure also produce elevated serum uric acid levels. The common analytical method for uric acid utilizes a spectrophotometric test that relies of the enzyme uricase. Because most mammals, with the exception of primates (including humans), express uricase, allantoin is the end degradation product of purines in most mammals. Uricase oxidizes uric acid to allantoin, producing hydrogen peroxide, which is measured in a chromogenic reaction. These assays are generally performed on discrete, random-access, automated autoanalyzers. |
| Because a single enzyme is responsible for the conversion of all ribonucleotides into deoxyribonucleotides, this enzyme is subject to a complex network of feedback regulation. The
enzyme contains several allosteric sites for metabolic regulation. Levels of the different dNTPs modify the enzyme activity toward the different NDPs. By regulating the enzymatic activity of deoxyribonucleotide synthesis as a function of the concentration of the different dNTPs, the cell insures that the proper ratios of the different deoxyribonucleotides are produced for normal growth, protein synthesis, and cell division.
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