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Query: EC:2.4.2.7 (
adenine phosphoribosyltransferase
)
692
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Many reports show that red blood cells of people exposed to lead have a decreased ATP concentration, decreased adenylate energy charge value and many metabolic and morphological abnormalities. Since the synthesis of nucleotides in erythrocytes occurs only through salvage pathways, we hypothesized that a decrease in nucleotide concentrations may be caused by lead-induced inhibition of erythrocyte phosphoribosyltransferases: adenine
APRT
(
EC 2.4.2.7
) and hypoxanthine-guanine HPRT (EC 2.4.2.8). These enzymes enable the reutilization of purine bases (adenine, guanine, hypoxanthine) converting them to mononucleotides (AMP,
GMP
, IMP), substrates for the synthesis of high-energy nucleotides. To confirm the hypothesis two experiments were performed: (i) in vitro, using a lysate of human erythrocytes incubated (5, 10, 30min) with lead ions (100microM, 10microM, 1microM, 500nM, 100nM lead acetate) and 100microM sodium acetate for the control, (ii) in vivo, using a lysate of rat erythrocytes taken from rats chronically exposed to lead (0.1% lead acetate in drinking water for 9 months, resulting in whole blood lead concentration 7microg/dL). The activities of
APRT
and HPRT were determined using HPLC method, which allowed concurrent determination of the activity of both enzymes in erythrocyte lysates. We have shown that, lead ions: (i) moderately inhibit both phosphoribosyltransferases in erythrocytes, this influence being detectable even at very low concentrations (ii) participate in hemolysis, the intensity of which negatively correlates with the activity of phosphoribosyltransferases. Our results indicate the necessity of further research on the role of lead-induced
APRT
and HPRT inhibition as one of the mechanisms of lead toxicity.
...
PMID:Inhibition of erythrocyte phosphoribosyltransferases (APRT and HPRT) by Pb2+: a potential mechanism of lead toxicity. 1942 46
Purine bases and nucleosides are produced by turnover of nucleotides and nucleic acids as well as from some cellular metabolic pathways. Adenosine released from the S-adenosyl-L-methionine cycle is linked to many methyltransferase reactions, such as the biosynthesis of caffeine and glycine betaine. Adenine is produced by the methionine cycles, which is related to other biosynthesis pathways, such those for the production of ethylene, nicotianamine and polyamines. These purine compounds are recycled for nucleotide biosynthesis by so-called "salvage pathways". However, the salvage pathways are not merely supplementary routes for nucleotide biosynthesis, but have essential functions in many plant processes. In plants, the major salvage enzymes are
adenine phosphoribosyltransferase
(
EC 2.4.2.7
) and adenosine kinase (EC 2.7.1.20). AMP produced by these enzymes is converted to ATP and utilised as an energy source as well as for nucleic acid synthesis. Hypoxanthine, guanine, inosine and guanosine are salvaged to IMP and
GMP
by hypoxanthine/guanine phosphoribosyltransferase (EC 2.4.2.8) and inosine/guanosine kinase (EC 2.7.1.73). In contrast to de novo purine nucleotide biosynthesis, synthesis by the salvage pathways is extremely favourable, energetically, for cells. In addition, operation of the salvage pathway reduces the intracellular levels of purine bases and nucleosides which inhibit other metabolic reactions. The purine salvage enzymes also catalyse the respective formation of cytokinin ribotides, from cytokinin bases, and cytokinin ribosides. Since cytokinin bases are the active form of cytokinin hormones, these enzymes act to maintain homeostasis of cellular cytokinin bioactivity. This article summarises current knowledge of purine salvage pathways and their possible function in plants and purine salvage activities associated with various physiological phenomena are reviewed.
...
PMID:Purine salvage in plants. 2930 99
The reversible
adenine phosphoribosyltransferase
enzyme (APRT) is essential for purine homeostasis in prokaryotes and eukaryotes. In humans, APRT (hAPRT) is the only enzyme known to produce AMP in cells from dietary adenine. APRT can also process adenine analogs, which are involved in plant development or neuronal homeostasis. However, the molecular mechanism underlying substrate specificity of APRT and catalysis in both directions of the reaction remains poorly understood. Here we present the crystal structures of hAPRT complexed to three cellular nucleotide analogs (hypoxanthine, IMP, and
GMP
) that we compare with the phosphate-bound enzyme. We established that binding to hAPRT is substrate shape-specific in the forward reaction, whereas it is base-specific in the reverse reaction. Furthermore, a quantum mechanics/molecular mechanics (QM/MM) analysis suggests that the forward reaction is mainly a nucleophilic substitution of type 2 (S
N
2) with a mix of S
N
1-type molecular mechanism. Based on our structural analysis, a magnesium-assisted S
N
2-type mechanism would be involved in the reverse reaction. These results provide a framework for understanding the molecular mechanism and substrate discrimination in both directions by APRTs. This knowledge can play an instrumental role in the design of inhibitors, such as antiparasitic agents, or adenine-based substrates.
...
PMID:Structural basis for substrate selectivity and nucleophilic substitution mechanisms in human adenine phosphoribosyltransferase catalyzed reaction. 3116 Mar 23
Guanosine monophosphate
, the precursor for riboflavin biosynthesis, can be converted to or generated from other purine compounds in purine metabolic networks. In this study, genes in these networks were manipulated in a riboflavin producer,
Bacillus subtilis
R, to test their contribution to riboflavin biosynthesis. Knocking out
adenine phosphoribosyltransferase
(
apt
), xanthine phosphoribosyltransferase (
xpt
), and adenine deaminase (
adeC
) increased the riboflavin production by 14.02, 6.78, and 41.50%, respectively, while other deletions in the salvage pathway, interconversion pathway, and nucleoside decomposition genes have no positive effects. The enhancement of riboflavin production in
apt
and
adeC
deletion mutants is dependent on the purine biosynthesis regulator PurR. Repression of ribonucleotide reductases (RNRs) led to a 13.12% increase of riboflavin production, which also increased in two RNR regulator mutants PerR and NrdR by 37.52 and 8.09%, respectively. The generation of deoxyribonucleoside competed for precursors with riboflavin biosynthesis, while other pathways do not contribute to the supply of precursors; nevertheless, they have regulatory effects.
...
PMID:Manipulation of Purine Metabolic Networks for Riboflavin Production in
Bacillus subtilis
. 3322 45
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