Nucleoside transport and associated metabolism*

Abstract

Nucleosides are intermediates of nucleotide metabolism. Nucleotide de novo synthesis generates the nucleoside monophosphates AMP and UMP, which are further processed to all purine and pyrimidine nucleotides involved in multiple cellular reactions, including the synthesis of nucleic acids. Catabolism of these substances results in the formation of nucleosides, which are further degraded by nucleoside hydrolase to nucleobases. Both nucleosides and nucleobases can be exchanged between cells and tissues through multiple isoforms of corresponding transport proteins. After uptake into a cell, nucleosides and nucleobases can undergo salvage reactions or catabolism. Whereas energy is preserved by salvage pathway reactions, catabolism liberates ammonia, which is then incorporated into amino acids. Keeping the balance between nitrogen consumption during nucleotide de novo synthesis and ammonia liberation by nucleotide catabolism is essential for correct plant development. Senescence and seed germination represent situations in plant development where marked fluctuations in nucleotide pools occur. Furthermore, extracellular nucleotide metabolism has become an immensely interesting research topic. In addition, selected aspects of nucleoside transport in yeast, protists and humans are discussed.

De Novo Pyrimidine Nucleotide Synthesis Mainly Occurs outside of Plastids, but a Previously Undiscovered Nucleobase Importer Provides Substrates for the Essential Salvage Pathway in Arabidopsis

“…Transport systems for nucleobases exist in Arabidopsis in a high number and are organized in different protein families (reviewed in Mö hlmann et al, 2010). However, among these proteins, there is no candidate with predicted plastidic localization.…”

“…For plants, this process is meaningful as nitrogen limitation often constrains growth. When nucleotides are degraded to the level of nucleosides or nucleobases, these intermediates can be exchanged between cells by corresponding transport proteins, allowing for a high flexibility of nucleotide metabolism at the level of tissues or whole organisms (Mö hlmann et al, 2010). Nucleosides or nucleobases can be recycled to nucleotides by the salvage pathway, which is less energy consuming compared with nucleotide de novo synthesis.…”

“…Nucleosides or nucleobases can be recycled to nucleotides by the salvage pathway, which is less energy consuming compared with nucleotide de novo synthesis. Whereas nucleotides can be exchanged between the cytosol, organelles, peroxisomes, and the endoplasmic reticulum, no significant transport is possible across the plasma membrane (Geigenberger et al, 2010;Mö hlmann et al, 2010). Therefore, nucleosides and nucleobases can be regarded as transport form of purine and pyrimidine metabolites.…”

Extra perspectives of 5-ethynyl-2′-deoxyuridine click reaction with fluorochrome azides to study cell cycle and deoxyribonucleoside metabolism

“…Thymine is a nitrogenous base unique for DNA; therefore, its nucleotides are involved only in the synthesis of this macromolecule, but the usage of somehow labeled dTTP for the identification of DNA synthesis in living cells, in plant cells in particular, is difficult because of plasmalemma poor permeability for nucleoside tri phosphates. However, nucleosides, including thymi dine (dT) penetrate the cell easily with the help of transporters [2]. Within the cell, dT is phosphorylated by specific thymidine kinase (TK; EC 2.7.1.21) or deoxyribonucleoside kinase (EC 2.7.1.145) to produce dTMP and further, in the process of successive kinase reactions, a dTTP is produced⎯a substrate for a DNA polymerase reaction.…”

Two nucleoside receptors from Streptomyces coelicolor: Expression of the genes and characterization of the recombinant proteins

“…Most bacteria exploit two pathways to produce nucleotides. One is de novo synthesis, and the other is the salvage pathway, which uses nucleotide precursors (nucleobases and nucleosides) from the environment [2]. Nucleosides pass through the cytoplasmic membrane with the help of multiple transporters.…”