Acidity continued purine

Studies on the structure of nucleic acids continue to be of great importance. X-ray crystallography, NMR and mass spectral characterisation are the most important techniques employed in this regard. Fluorescence studies of nucleic acids have been of interest for some time. Since none of the common nucleobases are intrinsically fluorescent, these studies normally involve the attachment of a fluorophore by a chemical linker. This year two studies have employed the fluorescent nucleobase 2-amino purine as a structural probe to observe conformational changes in RNA. Synthetic oligoribonucleotides in which the fluorescent nucleobase replaced one of the natural nucleobases were utilised in these... 

Urinary alkalinization- Urates tend to crystallize out of an acid urine therefore, a liberal fluid intake is recommended, as well as sufficient sodium bicarbonate (3 to 7.5 g/day) or potassium citrate (7.5 g/day) to maintain an alkaline urine continue alkalization until the serum uric acid level returns to normal limits and tophaceous deposits disappear. Thereafter, urinary alkalization and the restriction of purine-producing foods may be relaxed. 

Two other features deserve mention. First, there is evidence, especially in the de novo purine pathway, that the enzymes are present as large, multienzyme complexes in the cell, a recurring theme in our discussion of metabolism. Second, the cellular pools of nucleotides (other than ATP) are quite small, perhaps 1% or less of the amounts required to synthesize the cell s DNA. Therefore, cells must continue to synthesize nucleotides during nucleic acid synthesis, and in some cases nucleotide synthesis may limit the rates of DNA replication and transcription. Because of the importance of these processes in dividing cells, agents that inhibit nucleotide synthesis have become particularly important to modern medicine. 

Allantoin is the excretory product in most mammals other than primates. Most fish hydrolyze allantoin to allantoic acid, and some excrete that compound as an end product. However, most continue the hydrolysis to form urea and glyoxylate using peroxisomal enzymes.336 In some invertebrates the urea may be hydrolyzed further to ammonia. In organisms that hydrolyze uric acid to urea or ammonia, this pathway is used only for degradation of purines from nucleotides. Excess nitrogen from catabolism of amino acids either is excreted directly as ammonia or is converted to urea by the urea cycle (Fig. 24-10). 

Methotexate is an antineoplastic folic add analogue that blocks the conversion of dihydrofolate (FHj) to tetrahydro-folate (FH4) by binding to dihydrofolate reductase (DHFR) enzyme. Folate is essential for the normal synthesis of purines and pyrimidines, and therefore DNA and RNA. In order for folate to function as a cofactor, it must be reduced to FH by DHFR. Methotrexate binds to DHFR, prevents the conversion of FH2 to FH4, and, consequently, inhibits purine and pyrimidine synthesis. The antimetabolites are considered cell cycle specific, with most activity for cells in the S (synthesis) phase. With high-dose methotrexate, leucovorin rescue is often used to prevent severe toxicity to normal body tissues. Leucovorin (folinic acid) is a reduced form of folate (similar to FH ) that does not require the use of DHFR. Leucovorin is transported into healthy cells and is utilized for DNA and RNA synthesis. Tumor cells tend to have impaired transport mechanisms and usually cannot use leucovorin. Leucovorin is usually started within 24 to 36 hours of high-dose methotrexate administration and continues until methotrexate serum levels are below nontoxic levels (0.1 to 0.05 mol/L). 

---