Nucleoside triphosphate

A nucleoside triphosphate is a molecule containing a nitrogenous base bound to a 5-carbon sugar (either ribose or deoxyribose), with three phosphate groups bound to the sugar. They are the building blocks of both DNA and RNA, which are chains of nucleotides made through the processes of DNA replication and transcription. Nucleoside triphosphates also serve as a source of energy for cellular reactions and are involved in signalling pathways. A nucleoside triphosphate is a molecule containing a nitrogenous base bound to a 5-carbon sugar (either ribose or deoxyribose), with three phosphate groups bound to the sugar. They are the building blocks of both DNA and RNA, which are chains of nucleotides made through the processes of DNA replication and transcription. Nucleoside triphosphates also serve as a source of energy for cellular reactions and are involved in signalling pathways. Nucleoside triphosphates cannot be absorbed well, so they are typically synthesized within the cell. Synthesis pathways differ depending on the specific nucleoside triphosphate being made, but given the many important roles of nucleoside triphosphates, synthesis is tightly regulated in all cases. Nucleoside analogues may also be used to treat viral infections. For example, azidothymidine (AZT) is a nucleoside analogue used to prevent and treat HIV/AIDS. The term nucleoside refers to a nitrogenous base linked to a 5-carbon sugar (either ribose or deoxyribose). Nucleotides are nucleosides covalently linked to one or more phosphate groups. To provide information about the number of phosphates, nucleotides may instead be referred to as nucleoside (mono, di, or tri) phosphates. Thus, nucleoside triphosphates are a type of nucleotide. Nucleotides are commonly abbreviated with 3 letters (4 or 5 in case of deoxy- or dideoxy-nucleotides). The first letter indicates the identity of the nitrogenous base (e.g. A for adenine, G for guanine), the second letter indicates the number of phosphates (mono, di, tri), and the third letter is P, standing for phosphate. Nucleoside triphosphates that contain ribose as the sugar are conventionally abbreviated as NTPs, while nucleoside triphosphates containing deoxyribose as the sugar are abbreviated as dNTPs. For example, dATP stands for deoxyribose adenine triphosphate. NTPs are the building blocks of RNA, and dNTPs are the building blocks of DNA. The carbons of the sugar in a nucleoside triphosphate are numbered around the carbon ring starting from the original carbonyl of the sugar. Conventionally, the carbon numbers in a sugar are followed by the prime symbol (‘) to distinguish them from the carbons of the nitrogenous base. The nitrogenous base is linked to the 1’ carbon through a glycosidic bond, and the phosphate groups are covalently linked to the 5’ carbon. The first phosphate group linked to the sugar is termed the α-phosphate, the second is the β-phosphate, and the third is the γ-phosphate. The cellular processes of DNA replication and transcription involve DNA and RNA synthesis, respectively. DNA synthesis uses dNTPs as substrates, while RNA synthesis uses NTPs as substrates. NTPs cannot be converted directly to dNTPs. DNA contains four different nitrogenous bases: adenine, guanine, cytosine and thymine. RNA also contains adenine, guanine, and cytosine, but replaces thymine with uracil. Thus, DNA synthesis requires dATP, dGTP, dCTP, and dTTP as substrates, while RNA synthesis requires ATP, GTP, CTP, and UTP. Nucleic acid synthesis is catalyzed by either DNA polymerase or RNA polymerase for DNA and RNA synthesis respectively. These enzymes covalently link the free -OH group on the 3’ carbon of a growing chain of nucleotides to the α-phosphate on the 5’ carbon of the next (d)NTP, releasing the β- and γ-phosphate groups as pyrophosphate (PPi). This results in a phosphodiester linkage between the two (d)NTPs. The release of PPi provides the energy necessary for the reaction to occur. It is important to note that nucleic acid synthesis occurs exclusively in the 5’ to 3’ direction. Given their importance in the cell, the synthesis and degradation of nucleoside triphosphates is under tight control. This section focuses on nucleoside triphosphate metabolism in humans, but the process is fairly conserved among species. Nucleoside triphosphates cannot be absorbed well, so all nucleoside triphosphates are typically made de novo. The synthesis of ATP and GTP (purines) differs from the synthesis of CTP, TTP, and UTP (pyrimidines). Both purine and pyrimidine synthesis use phosphoribosyl pyrophosphate (PRPP) as a starting molecule. The conversion of NTPs to dNTPs can only be done in the diphosphate form. Typically a NTP has one phosphate removed to become a NDP, then is converted to a dNDP by an enzyme called ribonucleotide reductase, then a phosphate is added back to give a dNTP.