Thymine degradation

Menadione (79) has been shown by Krishna et al. to act as a photosensitizer for thymine degradation. Spin-trapping experiments with several nucleosides showed that the photosensitizations occurred by electron transfer from the substrate to the excited triplet state of menadione to form the cation radical of the substrate and the anion radical of menadione, both of which were detected... 

It connects with the Krebs cycle of the Main Powerhouse via the Urea Rest Room, as aspartate and glutamate, which are spun off the Krebs Cycle are important participants in die Urea Cycle. Also, 3-aminobutyrate, a product of thymine degradation, may connect to succinyl CoA. 

O-isopropylidene derivative (57) must exist in pyridine solution in a conformation which favors anhydro-ring formation rather than elimination. Considerable degradation occurred when the 5-iodo derivative (63) was treated with silver fluoride in pyridine (36). The products, which were isolated in small yield, were identified as thymine and l-[2-(5-methylfuryl)]-thymine (65). This same compound (65) was formed in high yield when the 5 -mesylate 64 was treated with potassium tert-hx Xy -ate in dimethyl sulfoxide (16). The formation of 65 from 63 or 64 clearly involves the rearrangement of an intermediate 2, 4 -diene. In a different approach to the problem of introducing terminal unsaturation into pento-furanoid nucleosides, Robins and co-workers (32,37) have employed mild base catalyzed E2 elimination reactions. Thus, treatment of the 5 -tosylate (59) with potassium tert-butylate in tert-butyl alcohol afforded a high yield of the 4 -ene (60) (37). This reaction may proceed via the 2,5 ... 

Wetzstein H-G, N Schmeer, W Karl (1997) Degradation of the fluoroquinolone enrofloxacin by the brown-rot fungus Gleophyllum striatum identification of metabolites. Appl Environ Microbiol 63 4272-4281. Wondrack LM, C-A Hsu, MT Abbott (1978) Thymine-7-hydroxylase and pyrimidine deoxyribonucleoside 2 -hydroxylase activities in Rhodotorula glutinis. J Biol Chem 253 6511-6515. 

J.C. Sutherland and Griffin incorporated tritium-labelled thymine into DNA and irradiated it with 313 nm light in buffered saline in the presence of p-aminobenzoic acid for up to 12 min. After separation of the products by TLC, the radioactivity was associated with a fraction which had the characteristic RF of dimers. When the hydrolysate from a 313 nm irradiated sample was re-irradiated at 254 nm and then chromatographed, the radioactivity had the mobility of thymine monomer. This is characteristic of pyrimidine cyclobutyl dimers which were known to be photosynthesized at 313 nm and photodegrad-ed to monomers at 254 nm. Although not degraded itself, the p-aminobenzoic acid clearly acted as a photosensitizer for the DNA-damaging thymine dimerization [40]. 

Dihydropyrimidine dehydrogenase is the first and the rate-limiting enzyme in the three-step metabolic pathway involved in the degradation of the pyrimidine bases uracil and thymine. In addition, this catabolic pathway is the only route for the synthesis of p-alanine in mammals. 

In other studies it was found that 5-alkyluracils inhibited the degradation of uracil and thymine by rat tissue supernatants. It is believed that these compounds are competitors for dihydrouracil dehydrogenase, which catalyses the reduction of uracil and thymine [278]. 

The principles underlying the degradation of purines (1) and pyrimidines (2) differ. In the human organism, purines are degraded into uric acid and excreted in this form. The purine ring remains intact in this process. In contrast, the ring of the pyrimidine bases (uracil, thymine, and cytosine) is broken down into small fragments, which can be returned to the metabolism or excreted (for further details, see p. 419). 

These bases are then degraded to two P-amino acids, uracil to P-alanine and thymine to P-aminoisobutyrate. 

There are no available data on the formation of hydroperoxides derived from DNA within cells. This is likely explained, at least partly, by the fact that DNA is a poorer target than proteins for OH radical as observed upon exposure of mouse myeloma cells to ionizing radiation . However, indirect evidence for DNA peroxidation within cells may be inferred from the measurement of final degradation products that may derive from thymine and guanine hydroperoxidation as the result of oxidation reactions mediated by OH radical and O2, respectively (Sections n.A.2 and n.E.2). It may be pointed out that the measurement of oxidized bases and nucleosides within DNA has been the subject of intense research during the last decade and accurate methods are now available . This includes DNA extraction that involves the chaotropic Nal precipitation step and the use of desferrioxamine to chelate transition metals in order to prevent spurious oxidation of overwhelming nucleobases to occur . HPLC coupled to electrospray ionization... 

Thymine 264.5 7.89 0.43 Slow conversion some hydrate much degrad. 90% conversion to a single dimer a minor product formed... 

Tuchman M, Ramnaraine ML, O Dea RF. Effects of uridine and thymidine on the degradation of 5-fluorouraeil, uraeil, and thymine by rat liver dihydropyrimidine dehydrogenase. Cancer Res 1985 45 5553-5556. 

Bacterial contamination of the urine may result in strongly increased levels of uracil due to the bacterial degradation of pseudouridine. Thymine-uraciluria, which is indicative of a dihydropyrimidine dehydrogenase or dihydropyrimidinase deficiency, may also result from increased tissue degradation. However, the latter situation is also characterized by hyper-/l-aminoisobutyric aciduria and hyper-/f-alaninuria [6]. Under alkaline conditions, due to the presence of bacterial contamination, the de-oxynucleosides may be hydrolyzed toward their corresponding nucleoside bases. 

The pathways for degradation of pyrimidines generally lead to NH4 production and thus to urea synthesis. Thymine, for example, is degraded to methyl-malonylsemialdehyde (Fig. 22-46), an intermediate of valine catabolism. It is further degraded through propionyl-CoA and methylmalonyl-CoA to succinyl-CoA (see Fig. 18-27). 

RGURE 22-46 Catabolism of a pyrimidine. Shown here is the pathway for thymine. The methylmalonylsemialdehyde is further degraded to succinyl-CoA. 

A common source of DNA damage is the spontaneous loss of the amine group on cytosine and the formation of an amide. This occurs at a rate of about 100 times a day. Fortunately, the body produces enzymes able to detect and repair such degraded cytosines. Given this information, suggest why DNA differs from RNA in possessing the nucleotide thymine rather than uracil. 

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