Purine aspartic acid

Aspartic acid and arginines are important substrates for the biosynthesis of purine bases. They are also glycosylation sites in proteins. These reasons have been at the origin of the synthesis of their mono and difluoro analogues. 

The dialkoxyphosphinydifluoromethyllithium reagent has also been used in the preparation of bioactive compounds such as 2-amino-7,7-difluoro-7-phos-phonoheptanoic acid for evaluation in the -methyl-D-aspartic acid binding assay [265], 9-(5,5-difluoro-5-phosphonopentyl)quanine as a multisubstrate analog inhibitor of purine nucleoside phosphorylase [266], fluorinated phosphoserine analog [267, 268] (Scheme 91) and nucleoside 5 -deoxy-5 -di-fluoromethylphosphonates [267,269] (Scheme 92). 

The atoms of the purine ring are contributed by a number of compounds, including amino acids (aspartic acid, glycine, and glutamine), CO2, and N10-formyltetrahydrofolate (Figure 22.5). The purine ring is constructed by a series of reactions that add the donated carbons and nitrogens to a preformed ribose 5-phosphate. (See p. 145 for a discussion of ribose 5-phosphate synthesis by the HMP pathway.)... 

The atoms of a purine are contributed by amino acids (aspartic acid, glutamine, and glycine), CO2, and N10-formyl tetrahydrofolic acid. 

A small number of other biosynthetic pathways, which are used by both photosynthetic and nonphotosynthetic organisms, are indicated in Fig. 10-1. For example, pyruvate is converted readily to the amino acid t-alanine and oxaloacetate to L-aspartic acid the latter, in turn, may be utilized in the biosynthesis of pyrimidines. Other amino acids, purines, and additional compounds needed for construction of cells are formed in pathways, most of which branch from some compound shown in Fig. 10-1 or from a point on one of the pathways shown in the figure. In virtually every instance biosynthesis is dependent upon a supply of energy furnished by the cleavage to ATP. In many cases it also requires one of the hydrogen carriers in a reduced form. While Fig. 10-1 outlines in briefest form a minute fraction of the metabolic pathways known, the ones shown are of central importance. 

All cells must be able to make pyrimidine and purine bases to be used in synthesis of nucleic acids and coenzymes. The pathway for synthesis of pyrimidine begins with aspartic acid and that for purines with glycine. In many organisms the pathway of purine formation is further enhanced because uric acid or a... 

Substances related to MSG and purine 5 -ribonucleotides include peptides, amino acids (e.g. cysteine, homocysteine, cysteine S-sulfonic acid, aspartic acid, a-amino adipic acid, a-methyl glutamic acid, tricholomic acid, ibotenic acid), pyrrolidone carboxylic acid, 3-methyl thiopropyl amine, and others [2, 10], They are of less commercial interest than MSG, IMP, and GMP. Chemical structures of some of these substances are depicted in Fig. 3.53. Relative umami effects of some are shown in Tab. 3.49. Tricholomic acid and ibotenic acid have been found in the mushrooms Tricholoma muscarium and Amanita stroboliformis, respectively. 

The utilization of ammonia resulting from the combination of carbamyl phosphate with aspartic acid, the initial reaction for the synthesis of the pyrimidine nucleotides, continues only as long as there is a requirement for them (Fig. 3). Regulation of this biosynthetic pathway is probably by way of feedback inhibition of aspartate transcarbamylase. The rat liver enzyme is inhibited by uridine, cytidine or thymidine or such derivatives as CMP, UTP, or TMP, all intermediates or products of this pathway (B8). This is not the only enzyme of the pathway which may be subject to feedback regulation. Dihydroorotase from rat liver is also inhibited by some pyrimidines and purines (B9). 

The isolation - of the 5-phosphate of N-(9-j3-D-ribofuranosyl-9 f-purin-6-yl)aspartic acid (26) from liver supports enzymic evidence ... 

Hundreds of neurotransmitters have since been identified. Some are small-molecule neurotransmitters, including ACh, monoamines (NE, DA, and 5-HT), amino acids (primarily glutamic acid, GABA, aspartic acid, and glycine), purines, (adenosine, ATP, GTP, and their derivatives), fatty acids (endogenous cannabinoids), and peptides (vasopressin, somatostatin, and neurotensin). Hormones, such as insulin or thyroxine, have distant effects on the cells of the body, as well as local effects. Single ions, such as zinc, which is secreted into synapses, also are neurotransmitters. 

In the biosynthesis of nucleosides, ribose combines with an intermediate from the initial stage of purine ring construction. It was found that the base portion was constructed from glycine and glutamine, and that a nitrogen atom originated from aspartic acid, and of the two Cj units one is derived from carbon dioxide and the other from a molecule of formic acid. 

One group of compounds that have proved to be particularly effective in interfering with DNA synthesis of tumour cells are the mercapto-purines and pyrimidines and their alkyl derivatives 6-mercaptopurine (6-MP) blocks the de novo synthesis of purines 9-(jS-D-arabinofuranosyl)-—9H—purine—6-thiol (ara—6-MP) inhibits the incorporation of L-aspartic acid and orotic acid into DNA cystosine 9-OS-D-xylo-furanosyl)—9H—purine—6-thiol (xyl—6-MP) inhibits the utilization of exogenously administered guanine the periodic acid oxidation product of 9-(/S-D-ribosyl)—6-methyl—thio purine (MMPR—OP) blocks the incorporation of thymidine into DNA . The effective clinical use of thiols... 

N-f 9-/l-D-Ribofuranosyl-9H-purin-6-yl)-L-aspartic acid, 9CI. 6-Succinamidopwine riboside [4542-23-8]... 

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