Nucleotide Conversions

The DNA Funhouse. The Main Powerhouse connects indirectly with the DNA Funhouse in that Main Powerhouse ingredients may indirectly become part of purine and pyrimidine nucleotides. Conversely, nucleic acid breakdown may contribute molecules that indirectly transform into Main Powerhouse molecules. 

The protein defective in Menkes disease is a membrane-bound protein consisting of 1500 amino acids. Evidence suggests that this protein occurs in the membrane of the endoplasmic reticulum, not in the plasma membrane. The mutations in the gene coding for Menkes protein that are responsible for the disease take a number of forms. The gene, as studied in hundreds of human subjects, may contain insertions (an extra nucleotide), deletions (one less nucleotide), conversions of an amino acid s codon to a stop codon (resulting in a truncated protein), and other types of mutations. 

Xanthine oxidase, mol wt ca 275,000, present in milk, Hver, and intestinal mucosa (131), is required in the cataboHsm of nucleotides. The free bases guanine and hypoxanthine from the nucleotides are converted to uric acid and xanthine in the intermediate. Xanthine oxidase cataly2es oxidation of hypoxanthine to xanthine and xanthine to uric acid. In these processes and in the oxidations cataly2ed by aldehyde oxidase, molecular oxygen is reduced to H2O2 (133). Xanthine oxidase is also involved in iron metaboHsm. Release of iron from ferritin requires reduction of Fe " to Fe " and reduced xanthine oxidase participates in this conversion (133). 

Introduction of the cobalt atom into the corrin ring is preceeded by conversion of hydrogenobyrinic acid to the diamide (34). The resultant cobalt(II) complex (35) is reduced to the cobalt(I) complex (36) prior to adenosylation to adenosylcobyrinic acid i7,i -diamide (37). Four of the six remaining carboxyhc acids are converted to primary amides (adenosylcobyric acid) (38) and the other amidated with (R)-l-amino-2-propanol to provide adenosylcobinamide (39). Completion of the nucleotide loop involves conversion to the monophosphate followed by reaction with guanosyl triphosphate to give diphosphate (40). Reaction with a-ribazole 5 -phosphate, derived biosyntheticaHy in several steps from riboflavin, and dephosphorylation completes the synthesis. 

The most conspicuous use of iron in biological systems is in our blood, where the erythrocytes are filled with the oxygen-binding protein hemoglobin. The red color of blood is due to the iron atom bound to the heme group in hemoglobin. Similar heme-bound iron atoms are present in a number of proteins involved in electron-transfer reactions, notably cytochromes. A chemically more sophisticated use of iron is found in an enzyme, ribo nucleotide reductase, that catalyzes the conversion of ribonucleotides to deoxyribonucleotides, an important step in the synthesis of the building blocks of DNA. 

Fukumori F, CP Saint (1997) Nucleotide sequences and regulational analysis of genes involved in conversion of aniline to catechol in Pseudomonas putida UCC22 (pTDNl). J Bacterial 179 399-408. 

Antipyrimidine antimetabolite inhibits DNA polymerase with inhibition of DNA strand elongation and replication activated in tumor cells in triphosphate form competes with conversion of cytidine to deoxycytidine nucleotides, further blocking polymerization of DNA leads to production of short DNS strands cell-cycle specific (S phase) acts only on proliferating cells. 

Pyrimidine 5 -nucleotidase (P5N) is a unique enzyme that was recognized from studies of families with relatively common hemolytic disorders. The enzyme catalyzes the hydrolytic dephosphorylation of pyrimidine 5 -nucleotides but not purine nucleotides. The role of this enzyme is to eliminate RNA and DNA degradation products from the cytosol during erythroid maturation by conversion of nucleotide monophosphates to diffusible nucleosides. P5N is inhibited by lead, and its activity is considered to be a good indicator of lead exposure (PI). 

Trinucleotides are formed by 5 -deprotection of the dinucleotide and subsequent conversion with the monotriazolide in the presence of N-methylimidazole. The fully protected di- and trideoxyribonucleotides of the following nucleotide sequences have been obtained in high yield T-T (82%), C-T (88%), C-C (84%), CM3 (81%), G-T (83%), A-G-T (65%), C-G-T (61%). The yields are similar to those obtained in a reaction involving l-(triisopropylbenzenesulfonyl)tetrazole as coupling agent(see also Section 12.7). 

Nucleotides containing the nucleobases T, G, and C are also subject to conversion in an analogous way. In place of CDI, caibonyldibenzimidazole, carbonyldi-1,2,4-triazole, and carbonyldibenzotriazole were utilized in these reactions. 

Peon J, Zewail AH (2001) DNA/RNA nucleotides and nucleosides direct measurement of excited-state lifetimes by femtosecond fluorescence up-conversion. Chem Phys Lett 348 255... 

Dunwiddie, T. V., Diao, L. Proctor, W. R. (1997b). Adenine nucleotides undergo rapid, quantitative conversion to adenosine in the extracellular space in rat hippocampus. J. Neurosci. 17 (20), 7673-82. 

The DszB enzyme encoded by the nucleotide sequence of ORF-2 catalyzes the conversion of HPBS to 2-hydroxybiphenyl and inorganic sulfur. 

Nitrosoarenes are readily formed by the oxidation of primary N-hydroxy arylamines and several mechanisms appear to be involved. These include 1) the metal-catalyzed oxidation/reduction to nitrosoarenes, azoxyarenes and arylamines (144) 2) the 02-dependent, metal-catalyzed oxidation to nitrosoarenes (145) 3) the 02-dependent, hemoglobin-mediated co-oxidation to nitrosoarenes and methe-moglobin (146) and 4) the 0 2-dependent conversion of N-hydroxy arylamines to nitrosoarenes, nitrosophenols and nitroarenes (147,148). Each of these processes can involve intermediate nitroxide radicals, superoxide anion radicals, hydrogen peroxide and hydroxyl radicals, all of which have been observed in model systems (149,151). Although these radicals are electrophilic and have been suggested to result in DNA damage (151,152), a causal relationship has not yet been established. Nitrosoarenes, on the other hand, are readily formed in in vitro metabolic incubations (2,153) and have been shown to react covalently with lipids (154), proteins (28,155) and GSH (17,156-159). Nitrosoarenes are also readily reduced to N-hydroxy arylamines by ascorbic acid (17,160) and by reduced pyridine nucleotides (9,161). 

---