Nucleotide inosinate

Transfer RNAs base-pair with mRNA codons at a three-base sequence on the tRNA called the anticodon. The first base of the codon in mRNA (read in the 5 —>3 direction) pairs with the third base of the anticodon (Fig. 27-8a). If the anticodon triplet of a tRNA recognized only one codon triplet through Watson-Criclc base pairing at all three positions, cells would have a different tRNA for each amino acid codon. This is not the case, however, because the anticodons in some tRNAs include the nucleotide inosinate (designated I), which contains the uncommon base hypoxanthine (see Fig. 8-5b). Inosinate can form hydrogen bonds with three different nucleotides (U, C, and A Fig. 27-8b), although... 

The pathway from PRPP to the first complete purine nucleotide, inosine monophosphate (IMP), involves 10 steps and is shown in figure 23.10. It would seem logical that the purine should be built up first, followed by addition of ri-bose-5-phosphate, but this is not the case. The starting point is PRPP, to which the imidazole ring is added the six-member ring is built up afterward. 

The nucleotide inosine 3, 5 -cyclic phosphate H20 [BEPRAP] crystallizes in the zwitterionic form. The free oxygen atoms of the phosphate accept two strong, salt-type hydrogen bonds from two N(l)-H groups. 0(6) and N(7) are not involved in hydrogen bonding (Fig. 17.63). 

The nucleotides inosine-5 -monophosphate and guanosine-5 -monophosphate, produced from yeast RNA are potent flavor potentiators for meat products. They act synergisticaHy with monosodium glutamate and are usually used in conjunction with this amino acid. 

Hypoxanthine is a base found in an intermediate of purine nucleotide biosynthesis. Figure 22.4 summarizes the pathway leading from phosphoribosyl-1-pyrophosphate (PRPP) to the first fully formed purine nucleotide, inosine 5 -monophosphate (IMP), also called inosinic acid. IMP contains as its base, hypoxanthine. 

In addition to salvaging purines, most cells interconvert adenine and guanine nucleotides. Inosine monophosphate (IMP), is the common intermediate. IMP is converted into AMP by a two-step reaction catalyzed by adenylosuccinate synthetase and adenylosuccinate lyase. Guanine nucleotides are formed in a two-step reaction in which IMP is converted into xanthine monophosphate (XMP) and then aminated to GMP. Both GMP and AMP can be reconverted into IMP. Mammalian cells can also deaminate adenosine to inosine and guanine to xanthine (Fig. 6.1). 

Subsequently, carbon 8 is provided by N °-formyl FTfj, nitrogen 3 by glutamine, carbon 6 by CO2, nitrogen 1 by aspartate, and carbon 2 by formyl tetrahydrofolate (see Fig. 41.1). Note that six molecules of ATP are required (starting with ribose 5-phosphate) to synthesize the first purine nucleotide, inosine monophosphate (IMP). This nucleotide contains the base hypoxanthine joined by an A-glycosidic bond from nitrogen 9 of the purine ring to carbon 1 of the ribose (Fig. 41.6). 

Fig. 41.10. Salvage of bases. The purine bases hypoxanthine and gnanine react with PRPP to form the nucleotides inosine and gnanosine monophosphate, respectively. The enzyme that catalyzes the reaction is hypoxanthine-gnanine phosphoribosyltransferase (HGPRT). Adenine forms AMP in a reaction catalyzed by adenine phosphoribosyltransferase (APRT). Nucleotides are converted to nucleosides by 5 -nucleotidase. Free bases are generated from nncleosides by purine nucleoside phosphorylase. Deamination of the base adenine occurs with AMP and adenosine deaminase. Of the purines, only adenosine can be directly phosphorylated back to a nucleotide, by adenosine kinase.

The Lesch-Nyhan syndrome is a rare, X-linked genetic disease due to a functional absence of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) (Seegmiller, Rosenbloom and Kelley, 1967). This enzyme catalyzes the transfer of the 5-phos-phoribosyl moiety of 5-phosphoribosyl-l-pyrophosphate (PP-ribose-P) to the purine bases guanine and hypoxanthine to form the nucleotides inosinic acid and guanylic acid. 

Kanno, N., Sato, M., and Sato, Y. (1990a) Enzymatic synthesis of a sulfate-containing nucleotide, inosine-5 -phosphosulfate, in several marine macroalgae. Biochem. Int., 21 (3), 519-528. 

The 5 nucleotide of inosine inosimc acid (CioHi3N40gP) is added to foods as a flavor enhancer What is the structure of mosinic acid" (The structure of inosine is given in Problem 28 21)... 

One of the steps in the biosynthesis of a nucleotide called inosine monophosphate is the formation of aminoimidazole ribonucleotide from formyjglycin-amidine ribonucleotide. Propose a mechanism. 

Inosine monophosphate dehydrogenase (EVDPDH) is a key enzyme of purine nucleotide biosynthesis. Purine synthesis in lymphocytes exclusively depends on the de novo synthesis, whereas other cells can generate purines via the so-called salvage pathway. Therefore, IMPDH inhibitors preferentially suppress DNA synthesis in activated lymphocytes. 

Inosine monophosphate dehydrogenase (IMPDH) is the key enzyme of purine nucleotide biosynthesis. Proliferation of activated lymphocytes dq ends on rapid de novo production of purine nucleotides for DNA synthesis. 

The first nucleotides to be investigated were inosinic and adenylic acids... 

A nucleoside consists of a purine or pyrimidine base linked to a pentose, either D-ribose to form a ribonucleo-side or 2-deoxy-D-ribose to form a deoxyribonucleoside. Three major purine bases and their corresponding ribo-nucleosides are adenine/adenosine, guanine/guanosine and hypoxanthine/inosine. The three major pyrimidines and their corresponding ribonucleosides are cytosine/ cytodine, uracil/uradine and thymine/thymidine. A nucleotide such as ATP (Fig. 17-1) is a phosphate or polyphosphate ester of a nucleoside. 

Adenosine is not a classical neurotransmitter because it is not stored in neuronal synaptic granules or released in quanta. It is generally thought of as a neuromodulator that gains access to the extracellular space in part from the breakdown of extracellular adenine nucleotides and in part by translocation from the cytoplasm of cells by nucleoside transport proteins, particularly in stressed or ischemic tissues (Fig. 17-2C). Extracellular adenosine is rapidly removed in part by reuptake into cells and conversion to AMP by adenosine kinase and in part by degradation to inosine by adenosine deaminases. Adenosine deaminase is mainly cytosolic but it also occurs as a cell surface ectoenzyme. 

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. 

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