Nucleotide Synthesis De Novo

Abstract

Nucleosides are composed of a heterocyclic ring (defined as the base) that is attached to a ribose. Addition of a phosphate to a nucleoside, at carbon 5 of the ribose, produces a nucleotide. Nucleotides function as ubiquitous building blocks for the synthesis of all nucleic acids, and also function in enzymatic reactions as cofactors and as a source of energy. These central metabolic roles require their continued biosynthesis from readily available precursors, and this process is defined as de novo nucleotide synthesis. The synthesis of purines starts with ribose‐phosphate, to which are attached the individual atoms of the heterocyclic base in a stepwise fashion. Pyrimidine synthesis starts with the stepwise formation of the base, to which is then added the ribose‐phosphate. Bases and nucleosides may also be recycled in salvage pathways. Key Concepts: Nucleotides form the building blocks for the synthesis of DNA and RNA, which store and transmit genetic information. They also serve as cofactors in many metabolic reactions. All four ribonucleoside triphosphates are important sources of energy for metabolic reactions, though ATP – being more abundant – is the most common cosubstrate in many metabolic reactions. Nucleotides are so essential to metabolism that genetic defects generally are lethal, and for humans only a few gene defects are observed, at a low frequency. Many of the enzymatic reactions in the de novo biosynthesis of nucleotides are combined as two or more reactions catalysed by a single multidomain protein. This has made nucleotide biosynthesis more efficient. For a few of the biosynthetic steps alternate enzymatic strategies have emerged between bacteria and vertebrates, and for such unique bacterial enzymes these present possible targets for drugs as selective antibiotics.

Science Rewritten to Accommodate its Origin

“…Reflection by ice in clouds and on Earth's surface like Marconi's trans-Atlantic radio waves delivered polarized light to tropical waters, Fig 1h . Nucleotide synthesis has been demonstrated. [37] Their phosphodiester bonds selectively absorbed ice light, polymerizing to form a pre-biotic DNA 'noodle soup'. DNA's greater stability than RNA favours it as life's precursor [38]: RNA's extra -OH group prevents minion formation.…”

A journey into the regulatory secrets of the de novo purine nucleotide biosynthesis

“…Because of its central position in metabolism, nucleotide pools need to be continuously replenished during highly demanding conditions, such as cell division. The pool of purine and pyrimidine nucleotides is ensured by two conserved pathways (schematized in Figure 1 for ribonucleotides): the salvage pathway that recycles free nitrogenous bases, and the de novo (which means “ of new ” in latin) biosynthesis pathway that produces nucleotides from carbon and nitrogen precursors ( Traut, 2014 ). The first pathway is less demanding in cellular energy and occurs exclusively in the cytoplasm.…”