Guanosinic acid

The first purine derivative being formed is inosine-5-monophosphate (inosinic acid), which holds a central position in primary purine metabolism. It is the precursor of adenosine-5 -monophosphate (adenosinic acid) as well as of guano-sine-5 -monophosphate (guanosinic acid), and these compounds may also be converted back to inosine-5 -monophosphate (Fig. 173). 

Folic acid is synthesized both in microorganisms and in plants. Guanosine-5-ttiphosphate (GTP) (33), -aminobenzoic acid (PABA), and L-glutamic acid are the precursors. Reviews are available for details (63,64). The sequence of reactions responsible for the enzymatic conversion of GTP to 7,8-dihydrofohc acid (2) is shown. 

Further efficient fermentative methods for manufacture of riboflavin have been patented one is culturing C. famata by restricting the carbon source uptake rate, thereby restricting growth in a linear manner by restriction of a micronutrient. By this method, productivity was increased to >0.17 g riboflavin/L/h (63). The other method, using Bacillus subtilis AJ 12644 low in guanosine monophosphate hydrolase activity, yielded cmde riboflavin 0.9 g/ L/3 days, when cultured in a medium including soy protein, salts, and amino acids (64). 

Microtubules can be reconstituted in vitro at 37 °C from a solution that contains a physiological mixture of brain tubulin, MAPs, small amounts of guanosine 5 -triphosphate (GTP), magnesium ions, and the calcium-chelating agent EGTA [ethylene glycol-bis(2-aminoethyl ether) N, N -tetraacetic acid]. Tubulin assembly is inhibited by low temperature and by the presence of calcium ions. 

Humans convert adenosine and guanosine to uric acid (Figure 34-8). Adenosine is first converted to inosine by adenosine deaminase. In mammals other than higher primates, uricase converts uric acid to the water-soluble product allantoin. However, since humans lack uricase, the end product of purine catabofism in humans is uric acid. 

Figure 4. Separation of ribonucleoside monophosphofic acids. Conditions 250-cm anion exchange column gradient, 0.01M KHgPO containing HsPOi, (pH 2.6) to 0.15M KHiFO in 30 min column tempera-ture, 70 C detector, UV at 254 nm. 1, cyti-dine-S -monophosphoric acid 2, uridine-5 -monophosphoric acid 3, adenosine-5 -mon-ophosphofic acid 4, inosine-5 -monophosphoric acid 5, 3, 5 -cyclic adenosine mono-phosphoric add 6, guanosine-5 -monophosphoric acid (36).

Recently, Switzer and co-workers have further extended the multi-stranded motifs for nucleic acids with the formation of a quintet assembly with oligonucleotides containing 2,deoxy-iso-guanosine (74). To support the quintet, metal ions larger than those appropriate for quartet stabilization were required, and Cs+ ions were found to best meet this requirement. From modeling studies, a structure in which a central Cs+ interacts with ten 02 iG atoms at a distance of 3.5 A was proposed. 

Not all analogues become active against cancer cells through incorporation into nucleic acid. Some analogues block the synthesis of normal purine and pyrimidine nucleotides for example, 8-azaguanine blocks guanosine monophosphate (GMP) synthesis and 6-mercaptopurine inhibits adenosine monophosphate (AMP) syn-thesis. 

Leslie Orgel and co-workers took up this problem and studied the non-enzymatic polymerisation of mononucleotides, i.e., the question as to whether single nucleic acid building blocks can undergo polycondensation on a corresponding complementary matrix. The substrates used were the 5 -phosphoimidazolides of adenosine (ImpA) and guanosine (ImpG), the matrices poly(U) and poly(C). 

Nucleic acids which contain only adenosine, guanosine and uridine are able to form A-U Watson-Crick pairs and G-U wobble pairs. They should be able to build up complex secondary and tertiary structures. 

Figure 11.4 Analysis of in vitro synthesized RNAs. 32P-Radiolabeled RNAs (48 nucleotides) capped with m7Gp3G (A and C) or m27,3 °Gp3G (B and D) were digested with either RNase T2 (A and C) or RNase T2 plus tobacco acid pyrophosphatase (TAP) (B and D) followed by anion-exchange HPLC on a Partisil 10SAX/25 column as described in the text. Fractions of 1 ml were collected, and the Cerenkov radiation was determined. The elution times of the following standard compounds, detected by ultraviolet (UV) absorption, are indicated with arrows 3,-CMP (Cp), S UMP (Up), 37-AMP (Ap), 3 -GMP (Gp), 3, 5 -m7GDP (pm7Gp), 3, 5 -GDP (pGp), 5 -GDP (p2G), 5 -GTP (p3G), and guanosine-SCtetraphosphate (P4G).

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