Adenosine 5 -nucleotides, chemical

All living organisms get their chemical energy from ATP and a hydride a reduced form of nicotinamide adenosine nucleotide diphosphate, NADH + H+, or its phosphorylated analog, NADPH + H+(Fig. 1.5). 

Hiratsuka, T. (1987) Nucleotide-induced change in the interaction between the 20- and 26-kilodalton heavy-chain segments of myosin adenosine triphosphatase revealed by chemical cross-linking via the reactive thiol SH2. Biochemistry 26, 3168. 

Figure 3.2 (a) The basic structure of a nucleotide, (b) The actual chemical structure of one representative nucleotide (adenylate, i.e. adenosine 5 -monophosphate)... 

Tipson devoted most of his years in Levene s laboratory accomplishing seminal work on the components of nucleic acids. To determine the ring forms of the ribose component of the ribonucleosides he applied Haworth s methylation technique and established the furanoid structure for the sugar in adenosine, guanosine, uridine, and thymidine. He showed that formation of a monotrityl ether is not a reliable proof for the presence of a primary alcohol group in a nucleoside, whereas a tosyl ester that is readily displaced by iodide affords clear evidence that the ester is at the 5-position of the pentofuranose. Acetonation of ribonucleosides was shown to give the 2, 3 -C -isopropyl-idene derivatives, which were to become extensively used in nucleoside and nucleotide chemistry, and were utilized by Tipson in the first chemical preparation of a ribonucleotide, inosinic acid. 

Julius Rebek and his group were also active at about the same time with enzyme-free self-replication of chemical structures. Unhke von Kiedrowski group, he did not use nucleotides, but a rephcator consisting of an adenosine derivative and a derivative of Kemp s acid (Rotello etal., 1991 Rebek, 1994). See also Figure 7.7 for a self-replicating system not based on nucleic-acid chemistry. There are several variations of this scheme, which are not illustrated here - for reviews see Sievers etal, 1994 Orgel, 1995. 

A variety of enzyme cofactors serving a wide range of chemical functions include adenosine as part of their structure (Fig. 8-41). They are unrelated structurally except for the presence of adenosine. In none of these cofactors does the adenosine portion participate directly in the primary function, but removal of adenosine generally results in a drastic reduction of cofactor activities. For example, removal of the adenine nucleotide (3 -phosphoadenosine diphosphate) from acetoacetyl-... 

Cells respond to their environment by taking cues from hormones or other external chemical signals. The interaction of these extracellular chemical signals ( first messengers ) with receptors on the cell surface often leads to the production of second messengers inside the cell, which in turn leads to adaptive changes in the cell interior (Chapter 12). Often, the second messenger is a nucleotide (Fig. 8-42). One of the most common is adenosine 3, 5 -cyclic monophosphate... 

Kinetic studies of the nucleotide analogs, y-phenylpropyl di- and triphosphate, have been undertaken to define the role of the adenosine residue in the chemical and enzymic reactions of adenosine triphosphate. A catalytic function associated with binding of metal ions at the adenine nitrogens has been ascribed to the adenosine moiety in phosphate transfer reactions in which adenosine di- or triphosphates function as the phosphate source109-"2. The pH-rate profile (Fig. 6) for the hydrolysis of -y-phenylpropyl diphosphate... 

The first scientific articles from the IKhPS were submitted for publication in the early 1960s, among them being Nikolay s reports on his work in the new field. His major project in nucleotide chemistry was specific chemical modifications of heterocyclic bases. Reactions of hydroxylamine with cytidine and uridine were studied in detail and a new reagent, O-methylhydroxylamine, was proposed for modification of cytidine. These investigations aimed at the development of efficient methods for sequencing and analysis of the secondary structure of polynucleotides. Later, a reaction of chloroacetaldehyde with adenosine and cytidine was discovered and used for preparation of fluorescent polynucleotide derivatives. 

Phosphorus is found in every cell of the body, but most of it (about 80% of the total) is combined with calcium as Ca3(P04)2 in the bones and teeth (Harper 1969 Tietz 1970). Phosphorus is present in cells mainly as organic phosphate, with a small amount in serum as inorganic phosphate (Tietz 1970). Phosphorus is involved in the intermediary metabolism of carbohydrates (Tietz 1970). About 10% is found in combination with proteins, phospholipids, and carbohydrates and in other compounds in the blood and muscle (Harper 1969). The remaining phosphorus is widely distributed in various chemical compounds such as nucleic acids, nucleotides, and adenosine triphosphate (ATP) (Tietz 1970). 

Reagents. Cyclic nucleotides (3, 5 -cyclic adenosine monophosphate (c-AMP), 3, 5 -cyclic guanosine monophosphate (c-GMP), and 3, 5 -cyclic inosine monophosphate (c-IMP)) sodium tetraborate hydrochloric acid and potassium hydroxide were purchased from Sigma Chemical Company, St. Louis, Missouri). Millex disposable filter units (0.22 pm) were obtained from Millipore Corporation (Bedford, Massachusetts). Triply distilled and deionized water was used for the preparation of buffer solutions. Both buffers and samples were routinely degassed with helium after filtration (using microfilter units). 

Nucleotides play central roles in metabolism. They serve as sources of chemical energy (ATP and guanosine triphosphate (GTP)), participate in cellular signalling (cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP)) and are incorporated into important cofactors of enzymatic reactions. Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA (Scheme 3). 

Fig. 17.2. Chemical structures of some nucleotides adenosine-5 -phosphate or 5 -adenylic acid adenosine-3 -phosphate or 3 -adenylic acid adenosine-3, S -disphosphate...

Fig. 20.1. Chemical structure of RNA with sequence. .. pApOpUpCp... or, in short, AOUC. All hydrogen atoms are drawn in adenosine, and only functional hydrogen atoms are given in the other nucleotide units. In DNA, hydroxyl groups in sugar 2 -position are replaced by hydrogen atoms, and uridine is methylated in 5-position and called thymidine [522]...

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