Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human B lymphoblast lines severely deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRT) were selected for resistance to 6-thioguanine from cloned normal and phosphoribosylpyrophosphate (PP-Rib-P) synthetase-superactive cell lines and were compared with their respective parental cell lines with regard to growth and PP-Rib-P and purine nucleotide metabolism. During blockade of purine synthesis de novo with 6-methylthioinosine or aminopterin, inhibition of growth of all HGPRT-deficient cell lines was refractory to addition of Ade at concentrations which restored substantial growth to parental cell lines. Ade-resistant inhibition of growth of parental lines by 6-methylthioinosine, however, occurred during Ado deaminase inhibition. Insufficient generation of IMP (and ultimately guanylates) to support growth of lymphoblasts lacking HGPRT activity and blocked in purine synthesis de novo best explained these findings, implying that a major route of interconversion of AMP to IMP involves the reaction sequence: AMP----Ado----Ino----Hyp----IMP. PP-Rib-P generation and purine nucleoside triphosphate pools were unchanged by introduction of HGPRT deficiency into normal lymphoblast lines, in agreement with the view that accelerated purine synthesis de novo in this deficiency results from increased availability of PP-Rib-P for the pathway. Cell lines with dual enzyme defects did not differ from PP-Rib-P synthetase-superactive parental lines in rates of PP-Rib-P and purine synthesis despite 5-6-fold increases in PP-Rib-P concentrations, excretion of nearly 50% of newly synthesized purines, and diminished GTP concentrations. Fixed rates of purine synthesis de novo in PP-Rib-P synthetase-superactive cells appeared to reflect saturation of the rate-limiting amidophosphoribosyltransferase reaction for PP-Rib-P. In combination with accelerated purine excretion, increased channeling of newly formed purines into adenylates, and impaired conversion of AMP to IMP, fixed rates of purine synthesis de novo may condition cell lines with defects in HGPRT and PP-Rib-P synthetase to depletion of GTP with consequent growth retardation.
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PMID:Regulation of purine nucleotide synthesis in human B lymphoblasts with both hypoxanthine-guanine phosphoribosyltransferase deficiency and phosphoribosylpyrophosphate synthetase superactivity. 131 6

Adenosine is a neuromodulator and potent vasoactive metabolite involved in various CNS regulatory mechanisms. We have recently shown that the newborn has maturationally related deficiency in adenosine production. The brains of Sprague-Dawley rats studied at ages 1, 7, 21 and 60 days (n = 6-12/group) showed that adenosine and its metabolites (measured by high-pressure liquid chromatography) is deficient in the newborn. Adenosine brain concentration was 0.99 nmol/g brain in newborn rats (day 0-1) and progressively increased postnatally to an adult value of 14.4 nmol/g brain. Inosine, a degradative product of adenosine by deaminase is significantly increased in newborns (mean +/- SEM = 48.3 +/- 14.3 nmol/g brain) relative to the 7-day-old rat (7.4 +/- 1.1 nmol/g brain) and to the adult (17.8 +/- 3.6 nmol/g brain). Thus, newborns have deficient adenosine brain concentration and this is due in part to increased deamination of adenosine. However, adenosine brain production may be augmented by ischemic-hypoxic insult. This was tested in 2 age groups of rats: 7 days old (n = 35) and adults (n = 35). Under nembutal anesthesia, bilateral carotid arteries were exposed and loosely tied, then both carotids were ligated and 5 animals from each group were decapitated and heads immediately frozen in liquid N2 at 5, 15, 30, 60, 120 and 300 s after ligation. Similar animals with carotids exposed but not ligated served as control (time zero). Brains were removed and assayed for adenosine and metabolites using high-pressure liquid chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ontogeny of adenosine production and degradation and its implications in neonatal cerebral blood flow regulation. 269 8

Inosine (I) at position 34 (wobble position) of tRNA is formed by the hydrolytic deamination of a genomically encoded adenosine (A). The enzyme catalyzing this reaction, termed tRNA A:34 deaminase, is the heterodimeric Tad2p/ADAT2.Tad3p/ADAT3 complex in eukaryotes. In budding yeast, deletion of each subunit is lethal, indicating that the wobble inosine tRNA modification is essential for viability; however, most of its physiological roles remain unknown. To identify novel cell cycle mutants in fission yeast, we isolated the tad3-1 mutant that is allelic to the tad3(+) gene encoding a homolog of budding yeast Tad3p. Interestingly, the tad3-1 mutant cells principally exhibited cell cycle-specific phenotype, namely temperature-sensitive and irreversible cell cycle arrest both in G(1) and G(2). Further analyses revealed that in the tad3-1 mutant cells, the S257N mutation that occurred in the catalytically inactive Tad3 subunit affected its association with catalytically active Tad2 subunit, leading to an impairment in the A to I conversion at position 34 of tRNA. In tad3-1 mutant cells, the overexpression of the tad3(+) gene completely suppressed the decreased tRNA inosine content. Notably, the overexpression of the tad2(+) gene partially suppressed the temperature-sensitive phenotype and the decreased tRNA inosine content, indicating that the tad3-1 mutant phenotype is because of the insufficient I(34) formation of tRNA. These results suggest that the wobble inosine tRNA modification is essential for cell cycle progression in the G(1)/S and G(2)/M transitions in fission yeast.
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PMID:Wobble inosine tRNA modification is essential to cell cycle progression in G(1)/S and G(2)/M transitions in fission yeast. 1787 41

Inosine is one of the most common modifications found in human RNAs and the Adenosine Deaminases that act on RNA (ADARs) are the main enzymes responsible for its production. ADARs were first discovered in the 1980s and since then our understanding of ADARs has advanced tremendously. For instance, it is now known that defective ADAR function can cause human diseases. Furthermore, recently solved crystal structures of the human ADAR2 deaminase bound to RNA have provided insights regarding the catalytic and substrate recognition mechanisms. In this chapter, we describe the occurrence of inosine in human RNAs and the newest perspective on the ADAR family of enzymes, including their substrate recognition, catalytic mechanism, regulation as well as the consequences of A-to-I editing, and their relation to human diseases.
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PMID:Adenosine Deaminases That Act on RNA (ADARs). 2860 Dec 23