Fact-checked by Grok 2 weeks ago

Nucleotide base

A nucleobase, also known as a nitrogenous base or nucleotide base, is a nitrogen-containing heterocyclic compound that serves as a key subunit of nucleotides, the monomeric units of nucleic acids DNA and RNA.^[1] These bases are organic molecules composed primarily of carbon, hydrogen, oxygen, and nitrogen atoms, and they attach to a sugar-phosphate backbone to form the informational polymers essential for genetic storage and transmission in living organisms.^[2] There are five canonical nucleobases: adenine (A) and guanine (G), which are purines featuring a double-ring structure, and cytosine (C), thymine (T), and uracil (U), which are pyrimidines with a single-ring structure.^[2] In DNA, the bases are adenine, guanine, cytosine, and thymine, where adenine pairs with thymine and guanine pairs with cytosine via hydrogen bonds to maintain the double-helix structure.^[1] In RNA, uracil replaces thymine, pairing with adenine, which enables roles in transcription, translation, and various regulatory functions.^[1] Nucleobases play critical roles beyond pairing, including stabilizing nucleic acid structures through π-π stacking interactions and contributing to the chemical diversity that underlies genetic fidelity and evolutionary selection pressures.^[2] Their specific hydrogen-bonding patterns ensure accurate replication and transcription, while modifications to these bases can influence gene expression, repair mechanisms, and responses to environmental stresses in biological systems.^[2]

Fundamentals

Definition and Classification

Nucleobases, also known as nitrogenous bases, are heterocyclic aromatic compounds containing nitrogen atoms that serve as the fundamental informational components of nucleotides in DNA and RNA.^[3] These molecules are attached to a sugar-phosphate backbone in nucleic acids, where they encode genetic information through specific sequencing.^[4] Nucleobases are broadly classified into two structural classes: purines and pyrimidines, distinguished by their ring architectures.^[5] Purines feature a bicyclic system composed of a fused six-membered pyrimidine ring and a five-membered imidazole ring, exemplified by adenine and guanine.^[6] In contrast, pyrimidines consist of a single six-membered ring with two nitrogen atoms, represented by cytosine, thymine (in DNA), and uracil (in RNA).^[5] This classification reflects their chemical composition and functional roles in forming the double helix of DNA via complementary base pairing, where a purine typically pairs with a pyrimidine. The nomenclature for these classes originated in the late 19th century amid early studies of organic compounds from biological sources. The term "purine" was introduced by German chemist Emil Fischer in 1884 to describe the hypothetical parent structure of uric acid derivatives, derived from the Latin purum uricum meaning "pure uric acid," after he isolated and later synthesized related compounds.^[7] The parent pyrimidine compound was first synthesized by Siegmund Gabriel in 1899, building on earlier work identifying pyrimidine derivatives in natural products like alloxan as early as 1818.^[8]

Biological Roles

Nucleobases serve as the fundamental units that encode genetic information in deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), where the linear sequence of these bases dictates the instructions for cellular functions, development, and heredity. In DNA, the four canonical nucleobases—adenine (A), thymine (T), guanine (G), and cytosine (C)—form the genetic code, while in RNA, uracil (U) replaces thymine. This sequence-specific arrangement allows nucleic acids to store and transmit hereditary information across generations, enabling the precise replication and expression of genes in living organisms.^[9] A key mechanism underlying this encoding is Watson-Crick base pairing, which stabilizes the double-helical structure of DNA and facilitates accurate replication and transcription. Adenine pairs specifically with thymine (or uracil in RNA) through two hydrogen bonds, while guanine pairs with cytosine through three hydrogen bonds, ensuring complementary strand alignment and fidelity in information transfer. This hydrogen bonding pattern, first elucidated in the double-helix model, underpins the semiconservative replication of DNA and the formation of RNA-DNA hybrids during gene expression.^[10] In transcription and translation, nucleobases play central roles in converting genetic information into functional proteins. During transcription, the DNA sequence is copied into messenger RNA (mRNA) by RNA polymerase, which reads the template strand and incorporates complementary ribonucleotides based on base-pairing rules. The resulting mRNA then travels to ribosomes, where its nucleobase sequence is decoded during translation: transfer RNA (tRNA) molecules recognize specific mRNA codons (triplets of bases) via anticodon base pairing, delivering corresponding amino acids to assemble polypeptides. This process directly links the nucleobase code to protein synthesis, regulating cellular metabolism, structure, and response to environmental cues.^[11]^[12] Beyond nucleic acids, nucleobases contribute to metabolic processes as precursors for essential coenzymes involved in energy transfer and redox reactions. For instance, adenine forms the core of adenosine triphosphate (ATP), the primary energy currency of cells, which hydrolyzes to release phosphate groups and drive endergonic reactions. Adenine also serves as a building block for nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD), coenzymes that facilitate electron transport in catabolic pathways like glycolysis and the citric acid cycle. These roles highlight nucleobases' versatility in supporting cellular energetics and biosynthesis.^[13]^[14] Alterations in nucleobase sequences, such as point mutations, can disrupt these functions and lead to genetic disorders. A well-documented example is sickle cell anemia, caused by a single adenine-to-thymine substitution in the beta-globin gene (HBB), changing the codon from GAG to GTG and replacing glutamic acid with valine at position 6 of the hemoglobin beta chain. This mutation promotes abnormal hemoglobin polymerization under low-oxygen conditions, resulting in distorted red blood cells, hemolytic anemia, and vaso-occlusive crises. Such base substitutions illustrate how nucleobase integrity is critical for maintaining protein function and overall health.^[15]^[16]

Chemical Properties

Molecular Structure

Nucleobases are heterocyclic organic compounds composed primarily of carbon, hydrogen, nitrogen, and oxygen atoms, forming the foundational units of nucleotides in nucleic acids. These molecules exhibit a planar, aromatic structure due to delocalized π-electrons across their ring systems, which contributes to their stability and role in base stacking interactions. The general architecture classifies them into two main categories: purines, which possess a bicyclic ring system, and pyrimidines, which feature a single ring. For instance, adenine has the molecular formula C₅H₅N₅, guanine C₅H₅N₅O, cytosine C₄H₅N₃O, thymine C₅H₆N₂O₂, and uracil C₄H₄N₂O₂.^[17]^[18]^[19]^[20]^[21] The purine ring system consists of a six-membered pyrimidine ring fused to a five-membered imidazole ring, creating a 9-atom bicyclic framework with nitrogens positioned at atoms 1, 3, 7, and 9. This fused structure is evident in adenine and guanine, where the pyrimidine ring includes alternating double bonds for aromaticity, and the imidazole ring contributes additional electron delocalization. In contrast, the pyrimidine ring system is a monocyclic, six-membered heterocycle with nitrogen atoms at positions 1 and 3, flanked by carbon atoms, as seen in cytosine, thymine, and uracil; this configuration allows for planarity and conjugation across the ring, enhancing aromatic character. The planarity of both purine and pyrimidine rings arises from sp² hybridization of the ring atoms, enabling efficient π-orbital overlap.^[6]^[22] Key functional groups on nucleobases include amino (-NH₂) and keto (=O) moieties, which influence their polarity and reactivity. For example, adenine features an amino group attached to carbon 6 (C6) of its purine ring, while guanine has an amino group at C2 and a keto group at C6. Cytosine bears an amino group at C4 and a keto group at C2 on its pyrimidine ring; thymine includes keto groups at C2 and C4, along with a methyl group at C5; and uracil has keto groups at both C2 and C4. In nucleotides, these bases connect to the sugar moiety via a β-N-glycosidic bond, typically at N9 for purines and N1 for pyrimidines, linking the base's nitrogen to the C1' of ribose or deoxyribose. These groups contribute to the molecules' partial hydrophilicity, though the overall solubility of free nucleobases in water is limited (e.g., adenine solubility ~0.5 g/L at 20°C), owing to the hydrophobic aromatic rings balanced by polar substituents.^[17]^[18]^[19]^[20]^[21] The aromaticity of nucleobases stems from their conjugated π-systems satisfying Hückel's rule (4n+2 π-electrons), with purines having 10 π-electrons and pyrimidines 6, promoting stability and planarity essential for nucleic acid conformation. This electron delocalization results in UV absorbance around 260 nm, a property exploited in biochemical quantification. Solubility is further modulated by the ring structure: purines, with larger hydrophobic surfaces, exhibit lower water solubility than pyrimidines, which have more exposed polar groups.^[23]

Tautomerism and Hydrogen Bonding

Nucleobases predominantly exist in their keto forms within DNA and RNA, where the equilibrium favors the keto tautomer over the enol form by several orders of magnitude, with enol populations typically below 0.1% at physiological pH.^[24] This keto-enol tautomerism involves the migration of a proton between a carbonyl oxygen and an adjacent hydroxyl group, potentially altering the hydrogen bonding patterns essential for base pairing. For instance, in thymine, the canonical keto form features a C4=O group, but the rare enol tautomer shifts the proton to form a C4-OH, enabling alternative pairing geometries.^[24] The tautomerization process can be represented for guanine as follows, where the keto form interconverts to the enol via proton transfer from N1 to O6:

\text{G(keto): } \ce{N1-H ... O6=C6} \rightleftharpoons \text{G(enol): } \ce{N1: ... HO-C6=}

This equilibrium highlights the dynamic proton migration that disrupts standard Watson-Crick configurations.^[25] Similarly, amino-imino tautomerism in bases like adenine or cytosine can occur, though keto-enol shifts are more directly linked to mutagenic potential.^[24] Hydrogen bonding in nucleobases relies on precise donor and acceptor sites on the Watson-Crick edge. In adenine, the N1 acts as an acceptor and the N6 amino group as a donor, facilitating two hydrogen bonds with thymine's N3-H donor and O4 acceptor. Guanine employs N1-H and N2-H as donors alongside O6 as an acceptor to form three bonds with cytosine's N3 acceptor, O2 acceptor, and N4-H donor. Thymine and uracil feature O2 and O4 as acceptors with N3-H as a donor. Tautomerism alters these sites—for example, the enol form of thymine converts O4 from an acceptor to a donor (O4-H), promoting non-standard interactions.^[26] These rare tautomers compromise replication fidelity by stabilizing mispairs, such as enol-thymine with guanine (mimicking A-T geometry) or enol-guanine with thymine (leading to G-T wobbles), resulting in A-C or G-T transitions after subsequent replication rounds.^[24] Such events occur without DNA damage, contributing to spontaneous mutation rates around 10^{-9} to 10^{-10} per base pair per generation.^[25] Spectroscopic techniques provide evidence for these tautomers; UV absorption spectra of nucleobases show distinct shifts, with keto forms absorbing around 260 nm and enol or imino tautomers exhibiting red-shifted bands near 280-300 nm due to altered π-conjugation.^[27] For example, UV resonance Raman spectroscopy has identified imino tautomers of cytosine derivatives through characteristic vibrational modes and absorption changes.^[27]

Canonical Nucleobases

Purine Bases

Purine bases refer to the two canonical nucleobases adenine and guanine, characterized by their fused bicyclic structure consisting of a pyrimidine ring fused to an imidazole ring.^[28] Adenine, chemically known as 6-aminopurine, features an amino group attached to the C6 position of the purine ring, which participates in hydrogen bonding during base pairing with thymine in DNA or uracil in RNA.^[17]^[28] It exhibits maximum ultraviolet absorbance at 260 nm, a property commonly used for quantifying nucleic acids in solution.^[28] In the B-form DNA double helix, the exocyclic amino group at C6 and the N7 atom of adenine project into the major groove, serving as recognition markers for sequence-specific protein binding.^[28]^[29] Guanine, or 2-amino-6-oxopurine, contains a keto group at C6 and an amino group at C2, forming a guanidino-like moiety that enables three hydrogen bonds in its pairing with cytosine.^[28] This triple hydrogen bonding pattern contributes to the higher thermal stability of guanine-cytosine base pairs compared to adenine-thymine pairs, resulting in elevated melting temperatures for GC-rich DNA duplexes.^[30]^[31] Guanine is particularly susceptible to oxidative damage, where reactive oxygen species convert it to 8-oxoguanine, a well-established biomarker of oxidative stress in DNA that can lead to transversion mutations if unrepaired.^[32] As larger bicyclic molecules compared to pyrimidines, both adenine and guanine exhibit low solubility in water at neutral pH due to their hydrophobic aromatic surfaces, which limits their free concentrations in aqueous biological environments. Guanine, in particular, shows a greater propensity for π-π stacking interactions than adenine, enhancing the stability of nucleic acid structures such as G-quadruplexes through favorable base overlap.^[33]^[34] Beyond their roles in genetic material, adenine serves as a component in cofactors like flavin adenine dinucleotide (FAD), which facilitates electron transfer in redox reactions.^[35] Guanine, incorporated into guanosine triphosphate (GTP), functions as an energy currency in processes such as protein synthesis and signal transduction, often hydrolyzing to guanosine diphosphate (GDP) to drive conformational changes in GTP-binding proteins.^[36]^[37]

Pyrimidine Bases

Pyrimidine bases are the single-ring nucleobases cytosine, thymine, and uracil, which play essential roles in nucleic acid structure and function.^[38] Cytosine, chemically known as 4-amino-2-oxopyrimidine, features an amino group at the 4-position and a keto group at the 2-position of the pyrimidine ring.^[19] A common spontaneous mutation involving cytosine is its hydrolytic deamination to uracil, which generates a U:G mismatch in DNA and contributes significantly to point mutations if unrepaired.^[39] Thymine, or 5-methyl-2,4-dioxopyrimidine, is distinguished by a methyl group at the 5-position of the pyrimidine ring, making it specific to DNA where it pairs with adenine.^[20] This base is particularly susceptible to ultraviolet (UV) radiation from sunlight, which induces the formation of thymine dimers, such as cyclobutane pyrimidine dimers between adjacent thymines, leading to DNA damage that can inhibit replication and cause mutations.^[40] Uracil, structured as 2,4-dioxopyrimidine with keto groups at positions 2 and 4, serves as the RNA-specific counterpart to thymine, pairing with adenine in RNA molecules.^[38] When uracil erroneously appears in DNA, often from cytosine deamination, it is recognized and removed by uracil-DNA glycosylase, which hydrolyzes the N-glycosidic bond to initiate base excision repair.^[41] Compared to purine bases, the smaller, single-ring structure of pyrimidine bases like cytosine, thymine, and uracil enhances their polarity and solubility in aqueous environments, facilitating their incorporation into nucleic acids.^[42] The methyl group at the C5 position in thymine further modulates its hydrophobicity relative to uracil, influencing base stacking and stability in DNA.^[20]

Modified Nucleobases

Types of Modifications

Modified nucleobases arise from various chemical alterations to the canonical purine and pyrimidine bases, expanding the functional diversity of nucleic acids while potentially compromising genomic integrity. These modifications include the addition of small alkyl groups, oxidation of ring structures, removal of functional groups, and formation of adducts with environmental agents. Such changes can occur through enzymatic catalysis or spontaneous reactions, often influencing the stability of base pairing in DNA and RNA double helices. Methylation involves the covalent addition of a methyl (CH₃) group to specific atoms on the nucleobase, typically at nitrogen or carbon positions. For instance, N⁶-methyladenine results from methylation at the N⁶ amino group of adenine, a modification prevalent in bacterial DNA. This process is primarily enzymatic, mediated by DNA methyltransferases that utilize S-adenosylmethionine as the methyl donor, flipping the target base out of the helix for precise addition. Methylation can stabilize or subtly alter base pairing; for example, 5-methylcytosine maintains Watson-Crick pairing with guanine but introduces steric effects that influence helix rigidity. Oxidation modifies nucleobases through the action of reactive oxygen species (ROS), such as hydroxyl radicals or singlet oxygen, leading to the incorporation of oxygen atoms into the ring structure. A prominent example is 8-oxoguanine, formed by oxidation at the C8 position of guanine, which arises from one-electron oxidation or radical addition mechanisms. These reactions are largely spontaneous, driven by cellular metabolic byproducts, though enzymatic pathways can contribute in some contexts. Oxidized bases like 8-oxoguanine disrupt base pairing stability, as the modified guanine can adopt a syn conformation to pair with adenine via Hoogsteen edges, promoting mutagenic G:C to T:A transversions. Deamination entails the hydrolytic removal of an amino group (-NH₂) from the nucleobase, converting it to a keto form. Cytosine deamination yields uracil by loss of the C4 amino group, a reaction that can proceed spontaneously via water addition or enzymatically through activation of a zinc-bound hydroxide nucleophile in deaminase active sites. This modification significantly alters base pairing, as uracil preferentially pairs with adenine instead of guanine, resulting in C:G to T:A mismatches during replication. Adenine and guanine deaminations to hypoxanthine and xanthine, respectively, follow similar mechanisms but occur less frequently. Alkylation adds alkyl groups (e.g., methyl or ethyl) to oxygen or nitrogen atoms on the bases, such as O⁶-methylguanine from nitrosamine exposure, via SN1 or SN2 nucleophilic substitutions. These are typically non-enzymatic, arising from exogenous alkylating agents like those in tobacco smoke, and destabilize base pairing; alkylated guanines pair erroneously with thymine, leading to mutations. Glycosylation involves the enzymatic attachment of sugar moieties, such as glucose, to oxygen atoms on hydroxylated nucleobases, as in base J (β-D-glucosyl-hydroxymethyluracil) in kinetoplastid DNA and glucosylated 5-hydroxymethylcytosine in bacteriophage T4 DNA.^[43] These modifications are rare in standard eukaryotic DNA but serve protective roles, such as against host restriction enzymes. Mechanisms of these modifications vary between enzymatic and spontaneous processes. Enzymatic modifications, such as methylation by DNA methyltransferases or deamination by APOBEC family enzymes, are site-specific and regulated, often serving epigenetic roles. In contrast, spontaneous reactions—like oxidation by ROS, deamination via hydrolysis, or alkylation by ambient electrophiles—occur randomly and contribute to mutagenesis if unrepaired. Overall, these alterations impact base pairing stability by changing hydrogen bond donors/acceptors or introducing steric bulk, which can weaken duplex formation or induce mispairing, thereby affecting replication fidelity and gene expression.

Biological Examples

In DNA, 5-methylcytosine serves as a key epigenetic modification primarily at CpG dinucleotides, where it plays a crucial role in gene regulation, X-chromosome inactivation, and imprinting in mammals by influencing chromatin structure and transcription factor binding.^[44] This modification is maintained through cell divisions by DNA methyltransferases, enabling heritable silencing of gene expression without altering the DNA sequence.^[45] Another prominent example is 8-oxoguanine, a major oxidative lesion formed by reactive oxygen species that acts as a biomarker for cellular oxidative stress and DNA damage, potentially leading to G-to-T transversions if unrepaired.^[46] In RNA, pseudouridine, an isomer of uridine, is one of the most abundant modifications in transfer RNA (tRNA), where it enhances structural stability by improving base stacking and rigidity of the sugar-phosphate backbone, thereby facilitating proper tRNA folding and function during translation.^[47] N6-methyladenosine, the most prevalent internal modification in eukaryotic messenger RNA (mRNA), regulates alternative splicing by recruiting splicing factors to specific sites, influencing exon inclusion and thereby modulating protein isoform diversity and gene expression.^[48] This dynamic mark is dynamically installed by methyltransferases and removed by demethylases, allowing rapid responses to cellular signals.^[49] Bacterial systems feature 7-methylguanosine in ribosomal RNA (rRNA), particularly at position 527 in the 16S rRNA decoding center of Escherichia coli, where it contributes to ribosome fidelity and confers resistance to certain antibiotics like streptomycin by stabilizing the rRNA structure.^[50] Queuosine, a 7-deazaguanosine derivative, modifies the wobble position (34) of tRNAs decoding glutamine, tyrosine, histidine, and asparagine codons in bacteria, enhancing translational accuracy and codon-anticodon recognition while suppressing frameshifting and nonsense suppression.^[51] This modification is acquired from the environment or synthesized de novo, linking bacterial metabolism to protein synthesis efficiency.^[52] From an evolutionary perspective, modified nucleobases like wybutosine—a tricyclic derivative at position 37 of phenylalanine tRNA in archaea—illustrate ancient adaptations for translational precision, with biosynthetic pathways conserved across archaeal lineages to prevent anticodon-codon slippage and ensure faithful decoding in extremophilic environments.^[53] These archaeal modifications highlight the diversification of tRNA hypermodifications predating eukaryotic innovations, supporting robust protein synthesis under harsh conditions. Cells employ base excision repair (BER) to address modified nucleobases arising from deamination (e.g., cytosine to uracil) or oxidation (e.g., guanine to 8-oxoguanine), initiating with glycosylases that excise the damaged base, creating an abasic site that is then processed by AP endonucleases, polymerases, and ligases to restore the genome.^[54] This pathway is essential for preventing mutations, with specific glycosylases like OGG1 targeting oxidized lesions and UNG handling deaminated bases, thereby maintaining genomic integrity across organisms.^[55]

Synthetic Nucleobases

Artificial Nucleobases

Artificial nucleobases are laboratory-synthesized compounds designed to replicate the structural and functional roles of natural nucleobases while introducing novel properties, such as expanded base-pairing capabilities or enhanced stability in synthetic nucleic acids. These molecules typically feature modified purine or pyrimidine scaffolds with altered hydrogen-bonding patterns to ensure orthogonality—meaning they pair specifically with complementary artificial partners without interfering with canonical A-T or G-C pairs. The development of artificial nucleobases began in the late 1980s, with Steven Benner's group reporting the first unnatural base pair, isoguanine (isoG) and isocytosine (isoC), which forms a stable, hydrogen-bonded pair analogous to G-C but with a rearranged donor-acceptor pattern. This milestone demonstrated that enzymes could incorporate and replicate non-natural bases in DNA, laying the foundation for artificially expanded genetic systems.^[56] Design principles for artificial nucleobases emphasize maintaining the size complementarity of natural bases—pairing larger purine-like structures with smaller pyrimidine-like ones—while reconfiguring hydrogen-bonding faces to avoid cross-pairing with endogenous bases. For instance, orthogonal hydrogen-bonding patterns, such as donor-acceptor-donor (DAD) or acceptor-donor-acceptor (ADA), are engineered to match complementary patterns exclusively, enhancing duplex stability and specificity.^[57] These designs often prioritize thermal stability comparable to or exceeding natural pairs; the dZ:dP pair, for example, contributes more to duplex stability than A:T or G:C under physiological conditions due to its three hydrogen bonds and minimal steric disruption. Such orthogonality minimizes mispairing, with replication fidelities exceeding 99% in polymerase-catalyzed reactions.^[57] Key examples include 2-aminopurine (2AP), a fluorescent purine analog of adenine that substitutes without significantly distorting DNA or RNA helices, allowing real-time monitoring of base dynamics via its enhanced fluorescence upon base stacking.^[58] For universal base pairing, synthetic analogs of inosine, such as 5-nitroindole or 3-nitropyrrole derivatives, enable non-discriminatory pairing with A, T, G, or C, facilitating applications in degenerate primers where sequence ambiguity is needed; these analogs form stable pairs through hydrophobic or weak hydrogen-bonding interactions rather than strict Watson-Crick geometry.^[59] Another prominent pair is dZ (6-amino-5-nitropyridin-2(1H)-one) and dP (2-amino-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one), developed in the 2000s, which exemplifies orthogonal hydrogen bonding with a DAD:ADA pattern, enabling replication in PCR with >97% efficiency using polymerases like Vent (exo-).^[57] Synthesis of artificial nucleobases commonly employs variants of the Traube purine synthesis, a ring-building approach starting from substituted pyrimidines or amidines, followed by cyclization with formic acid or orthoesters to form the imidazole ring.^[60] For instance, 2-aminopurine is prepared by nitrosation of 4,6-diaminopyrimidine, reduction to the diamine, and Traube cyclization, yielding the purine core in high yield under mild conditions.^[60] Similarly, isoG and related analogs are synthesized via Traube-like annulation of pyrimidine precursors with altered substituents to introduce the desired hydrogen-bonding motifs, often followed by glycosylation to attach the deoxyribose.^[61] These methods allow precise control over functional groups, ensuring compatibility with enzymatic incorporation.

Applications in Biotechnology

Synthetic nucleobases have revolutionized biotechnology by enabling the expansion of the genetic code beyond the natural four-letter alphabet, allowing for the incorporation of additional base pairs in DNA and RNA systems. In the 2010s, researchers developed unnatural base pairs (UBPs) such as d5SICS–dNaM, which were successfully replicated by polymerases, creating semi-synthetic organisms capable of storing and retrieving eight base pairs of genetic information with high fidelity, up to 98.5% for certain unnatural codons. These advancements, including the creation of the first semi-synthetic organism in 2014, have facilitated applications in synthetic biology for encoding novel amino acids and functions not possible with natural bases. Xenonucleic acids (XNAs) incorporating unnatural bases further extend this by supporting enzymatic synthesis and evolution, enabling the storage of genetic information in non-DNA backbones for diverse biotechnological uses.^[62] In polymerase chain reaction (PCR) and sequencing, modified oligonucleotides, such as those incorporating locked nucleic acid (LNA) modifications, enhance specificity and sensitivity by increasing primer-template binding affinity. LNA incorporation into primers allows detection of as little as 5 pg of template DNA, significantly improving amplification performance in real-time PCR and enabling clearer sequencing reads in AT-rich regions. This modification supports multiplexing and allele-specific detection, as demonstrated in SNP genotyping assays where LNA probes achieve higher discrimination than standard probes. LNAs' constrained ribose conformation minimizes mismatches, making them ideal for challenging sequences in diagnostic and research applications.^[63] Artificial nucleobases play a critical role in therapeutics through their integration into aptamers and antisense oligonucleotides, improving stability and efficacy. For instance, aptamers with 2'-fluoro-modified pyrimidine nucleotides enhance nuclease resistance while maintaining high binding affinity to targets like HIV-1 reverse transcriptase, optimizing properties beyond mere stability. In antisense therapies, 2'-fluoro pyrimidine nucleotides are used in chimeric oligonucleotides to promote exon skipping, as seen in treatments for muscular dystrophy where LNA/2'-F hybrids outperform unmodified versions in efficiency. Approved drugs like pegaptanib (Macugen), an anti-VEGF aptamer containing 2'-fluoro-modified pyrimidines, exemplify their clinical impact in treating age-related macular degeneration by providing targeted inhibition with prolonged serum half-life.^[64] For diagnostics, fluorescent nucleobase analogs enable real-time monitoring in PCR without external probes, offering a cost-effective alternative to traditional methods. Analogs like pyrrolo-dC (PdC) incorporated into primers exhibit signal-off fluorescence during amplification, allowing quantitative detection of pathogens such as Chlamydia trachomatis with linearity from 10^4 to 10^8 copies and R² > 0.99. Signal-on approaches using universal fluorescent bases in overhang primers detect targets like Mycoplasma hominis via hydrolysis-induced emission, surpassing SYBR Green in specificity and sensitivity for clinical nucleic acid quantification.^[65] As of 2024, advancements include enzyme-assisted nanopore sequencing of expanded genetic alphabets with high-fidelity replication of hydrophobic UBPs, and improved synthesis of the unnatural base NaM for enhanced orthogonality in in vitro transcription and translation, broadening applications in synthetic biology.^[66]^[67]

Origins and Biosynthesis

Biosynthetic Pathways

De novo purine biosynthesis occurs through a 10-step enzymatic pathway that assembles the purine ring on a ribose-5-phosphate backbone, starting from 5-phosphoribosyl-1-pyrophosphate (PRPP) and culminating in inosine monophosphate (IMP). The committed and rate-limiting step is catalyzed by amidophosphoribosyltransferase (also known as glutamine-PRPP amidotransferase or PPAT), which converts PRPP and glutamine to 5-phosphoribosylamine, releasing pyrophosphate and glutamate. Subsequent steps involve the addition of glycine, formyl groups from tetrahydrofolate, and contributions from aspartate, CO₂, and additional ATP molecules, mediated by enzymes such as phosphoribosylglycinamide formyltransferase (GART), phosphoribosylaminoimidazole-succinocarboxamide synthase (PAICS), and others, ultimately forming IMP. From IMP, the pathway branches: adenylosuccinate synthase and lyase convert IMP to adenosine monophosphate (AMP), while IMP dehydrogenase and GMP synthase produce guanosine monophosphate (GMP). This pathway was elucidated in the 1950s through pioneering work on pigeon liver extracts, establishing the sequence of intermediates and enzyme reactions.^[68]^[69] De novo pyrimidine biosynthesis proceeds via a six-step pathway that builds the pyrimidine ring separately before attaching it to PRPP, beginning with the formation of carbamoyl phosphate from glutamine, bicarbonate, and two ATP molecules, catalyzed by carbamoyl phosphate synthetase II (CPSII). In animals, the first three steps—CPSII, aspartate transcarbamoylase (ATCase), and dihydroorotase (DHOase)—are integrated into a single multifunctional protein known as CAD (or trifunctional protein), which assembles into a 1.5 MDa hexamer to channel intermediates efficiently and prevent their diffusion. The remaining steps involve dihydroorotate dehydrogenase (producing orotate), orotate phosphoribosyltransferase, and orotidine-5'-monophosphate decarboxylase (often fused as UMP synthase in eukaryotes), yielding uridine monophosphate (UMP); UMP is then converted to cytidine monophosphate (CMP) and thymidine monophosphate (TMP). This pathway ensures balanced production of pyrimidine nucleotides essential for nucleic acid synthesis.^[70]^[71] Salvage pathways recycle free purine bases, conserving energy compared to de novo synthesis by reutilizing hypoxanthine, guanine, and adenine through phosphoribosyltransferases. A key enzyme is hypoxanthine-guanine phosphoribosyltransferase (HGPRT), which catalyzes the transfer of the phosphoribosyl group from PRPP to hypoxanthine (forming IMP) or guanine (forming GMP), preventing accumulation of these bases and reducing uric acid overproduction. Defects in HGPRT, resulting from mutations in the HPRT1 gene, cause Lesch-Nyhan syndrome, an X-linked disorder characterized by hyperuricemia, neurological dysfunction, and self-injurious behavior due to <1.5% residual enzyme activity. Pyrimidine salvage similarly involves enzymes like uracil phosphoribosyltransferase to form UMP from uracil. These pathways are particularly vital in tissues with high nucleotide turnover.^[72]^[73] Regulation of these biosynthetic pathways primarily occurs through feedback inhibition to match nucleotide production with cellular demand and prevent toxic imbalances. In purine biosynthesis, AMP and GMP synergistically inhibit amidophosphoribosyltransferase allosterically, while IMP dehydrogenase is inhibited by GMP and xanthosine monophosphate (XMP); additional control involves GTP stimulating AMP synthesis and ATP promoting GMP production to balance adenine and guanine nucleotides. Pyrimidine biosynthesis is regulated at the CAD protein, where UTP inhibits CPSII, and ATP activates it, ensuring coordination with purine levels; in bacteria, aspartate transcarbamoylase is feedback-inhibited by CTP. Transcriptional controls, such as the PurR repressor in bacteria or c-Myc induction in mammals, further modulate enzyme expression based on purine availability. Post-translational modifications, including phosphorylation of pathway enzymes, also fine-tune activity in response to metabolic signals like mTORC1 activation.^[74]^[73] Organismal variations reflect evolutionary adaptations in enzyme organization and pathway integration. In animals, purine enzymes form dynamic purinosomes for efficient channeling, while pyrimidine synthesis features the multifunctional CAD protein and separate carbamoyl phosphate synthetases for pyrimidine and urea/arginine pathways; salvage is prominent but de novo dominates in proliferating cells. Plants lack the CAD complex and purinosome, instead using separate enzymes for pyrimidine steps with a single carbamoyl phosphate synthetase serving both pyrimidine and arginine biosynthesis, and they exhibit robust salvage under nutrient stress, such as phosphate limitation, to recycle purines efficiently. Bacteria typically have discrete enzymes without large multifunctional complexes, though gene fusions are common (e.g., in purine pathways), and they often rely more on de novo synthesis with stringent transcriptional regulation via repressors like PurR; some bacterial species show pathway variations, such as alternative aspartate utilization in pyrimidines. These differences influence metabolic flexibility, with plants emphasizing salvage for growth in variable environments and bacteria optimizing for rapid replication.^[75]^[76]^[70]

Prebiotic Synthesis

The prebiotic synthesis of nucleotide bases refers to abiotic chemical processes that could have formed these molecules under conditions mimicking the early Earth environment, providing building blocks for RNA and the hypothesized RNA world. Early experiments simulating primordial atmospheres demonstrated the potential for generating simple organic precursors to nucleobases. In the landmark Miller-Urey experiment of 1953, electrical discharges in a reducing gas mixture of methane, ammonia, hydrogen, and water vapor produced amino acids and simple heterocyclic compounds, which served as precursors to nucleobases such as those found in RNA.^[77] Subsequent analyses of these experiments confirmed the formation of adenine and other purine-like heterocycles in trace amounts, highlighting the role of spark discharges in generating complex organics from inorganic gases.^[77] A key challenge in prebiotic nucleotide assembly was the formation of the sugar component, ribose, which is essential for coupling with bases. The formose reaction, a base-catalyzed aldol condensation of formaldehyde, yields a complex mixture of sugars including ribose and sugar-like molecules that could mimic base precursors, occurring under alkaline aqueous conditions plausible for early oceans or ponds.^[78] However, this reaction produces ribose in low yields (typically less than 1%) amid a tarry mixture of branched and straight-chain polyols, complicating selective incorporation into nucleotides.^[78] Specific pathways for purine base formation have been elucidated through simulations of prebiotic chemistry. Adenine, a canonical purine, was synthesized via polymerization of hydrogen cyanide (HCN) in aqueous ammonia solutions heated to moderate temperatures, yielding up to several percent adenine from concentrated HCN (1-15 M), as demonstrated in experiments modeling primitive Earth conditions.^[79] For guanine, another purine base, prebiotic routes involve intermediates like glycinamide, where a one-step reaction with formamide under heating produces hypoxanthine—a direct precursor to guanine—in yields suitable for further transformation, bypassing multi-step enzymatic processes.^[80] The coupling of nucleobases with ribose to form nucleosides remains a critical step, addressed through non-enzymatic mechanisms like wet-dry cycles that concentrate reactants and drive dehydration. In a seminal 2009 study, pyrimidine nucleosides were formed plausibly from simple precursors like cyanamide, glycolaldehyde, and phosphate under UV irradiation and drying-rewetting conditions, yielding activated ribonucleotides without free ribose or isolated bases, thus avoiding unstable intermediates.^[81] These cycles mimic evaporative pools on early Earth, promoting phosphorylation and glycosylation in a single sequence.^[81] Despite these advances, prebiotic synthesis faces significant hurdles, including low overall yields (often below 10% for key products) and racemization, where chiral centers in sugars and amino acid precursors form equal mixtures of enantiomers, reducing the stereospecificity needed for functional biopolymers.^[82] Recent findings from the 2020s have highlighted mineral catalysis as a mitigating factor; for instance, montmorillonite clays facilitate the adsorption and polymerization of nucleotides, enhancing yields of oligomers by concentrating monomers and stabilizing intermediates against hydrolysis in dilute solutions.^[83] These clays, abundant in volcanic or hydrothermal settings, promote selective β-anomer formation and chain elongation up to 50-100 mers under cycling conditions.^[83] This abiotic self-assembly of nucleotides underpins the RNA world hypothesis, positing that RNA emerged as both genetic material and catalyst through spontaneous oligomerization from prebiotic pools, enabling replication and evolution without proteins.^[84] Such processes could have led to protocells with functional RNA networks, bridging chemistry to biology.^[84]

References

[1]
Nucleotide - National Human Genome Research Institute
A nucleotide is the basic building block of nucleic acids (RNA and DNA). A nucleotide consists of a sugar molecule (either ribose in RNA or deoxyribose in DNA)
[2]
On the Origin of the Canonical Nucleobases - PubMed Central - NIH
The contemporary composition of nucleobases is a result of multiple selection pressures that operated during early chemical and biological evolution.
[3]
[PDF] A search for amino acids and nucleobases in the Martian meteorite ...
Nucleobases are nitrogen heterocyclic compounds that are essential components of the informational monomers of ribonucleic acid (RNA) and deoxyribonucleic ...
[4]
De Novo Nucleic Acids: A Review of Synthetic Alternatives to DNA ...
Dec 11, 2020 · The latter consist of three molecular components; a heterocyclic aromatic base (also known as a nucleobase), a five-atom ring sugar, and a ...
[5]
DNA and RNA - Computational Medicine Center
Bases are classified into two types: the purines, A and G, and the pyrimidines, the six-membered rings C, T and U. Uracil (U), takes the place of thymine in ...
[6]
Structure–activity features of purines and their receptors
Jan 26, 2022 · The purine molecular structure consists of fused pyrimidine and imidazole rings. Purines are main pieces that conform the structure of ...Missing: source:.
[7]
Emil Fischer – Biographical - NobelPrize.org
This parent substance, which at first he regarded as being hypothetical, he called purine in 1884, and he synthesized it in 1898. Numerous artificial ...
[8]
Believe It or Not: Carbon Protonation of the Pyrimidine Ring
Pyrimidine was first synthesized by Gabriel (1899). All the knowledge accumulated over more than a 100 years accentuates the basic character of the ...
[9]
The Structure and Function of DNA - Molecular Biology of the Cell
120-121), nucleotides are composed of a five-carbon sugar to which are attached one or more phosphate groups and a nitrogen-containing base. In the case of ...<|control11|><|separator|>
[10]
https://www.nature.com/scitable/topicpage/discovery-of-dna-structure-and-function-watson-397/
[11]
Translation: DNA to mRNA to Protein | Learn Science at Scitable
The process of translation can be seen as the decoding of instructions for making proteins, involving mRNA in transcription as well as tRNA.
[12]
From RNA to Protein - Molecular Biology of the Cell - NCBI Bookshelf
Once an mRNA has been produced, by transcription and processing the information present in its nucleotide sequence is used to synthesize a protein.
[13]
Role of Nicotinamide Adenine Dinucleotide and Related Precursors ...
Recent studies have shown that enhancing NAD + levels can profoundly reduce oxidative cell damage in catabolic tissue, including the brain.
[14]
Nucleotide Coenzymes - an overview | ScienceDirect Topics
Nucleotide coenzymes are defined as essential components of intracellular respiratory mechanisms that include pyridine nucleotides, such as niacin (nicotinamide) ...
[15]
HBB gene: MedlinePlus Genetics
Mar 14, 2024 · The HBB gene provides instructions for making a protein called beta-globin. Beta-globin is a component (subunit) of a larger protein called hemoglobin.
[16]
Sickle Cell Disease—Genetics, Pathophysiology, Clinical ...
May 7, 2019 · Sickle cell disease (SCD) is a monogenetic disorder due to a single base-pair point mutation in the β-globin gene resulting in the substitution ...
[17]
Adenine | C5H5N5 | CID 190 - PubChem - NIH
Adenine is the parent compound of the 6-aminopurines, composed of a purine having an amino group at C-6. It has a role as a human metabolite.
[18]
Guanine | C5H5N5O | CID 135398634 - PubChem - NIH
Guanine | C5H5N5O | CID 135398634 - structure, chemical names, physical and chemical ... Molecular Formula. C5H5N5O. Synonyms. guanine; 73-40-5; 2-Amino-6 ...
[19]
Cytosine | C4H5N3O | CID 597 - PubChem - NIH
Cytosine | C4H5N3O | CID 597 - structure, chemical names, physical and chemical ... Molecular Formula. C4H5N3O. Synonyms. cytosine; 71-30-7; 4-Amino-2 ...
[20]
Thymine | C5H6N2O2 | CID 1135 - PubChem - NIH
Thymine is a pyrimidine nucleobase that is uracil in which the hydrogen at position 5 is replaced by a methyl group.
[21]
https://webbook.nist.gov/cgi/cbook.cgi?ID=C66228
[22]
Purine and Pyrimidine Metabolism
Apr 12, 1997 · Pyrimidine synthesis begins with carbamoyl phosphate synthesized in the cytosol of those tissues capable of making pyrimidines (highest in ...
[23]
Pyrimidine - Wikipedia
Occurrence and history The systematic study of pyrimidines began in 1884 with Pinner, who synthesized derivatives by condensing ethyl acetoacetate with ...
[24]
Aromaticity of nucleic acid bases - Wiley Interdisciplinary Reviews
Dec 13, 2020 · This review puts the spotlight on interplay between aromaticity of purine and pyrimidine nucleobases and their tautomeric preferences.Missing: physical planarity solubility
[25]
Structural Insights Into Tautomeric Dynamics in Nucleic Acids ... - NIH
During DNA replication, formation of minor tautomeric forms of nucleobases could lead to mispairing that generates mutations in the absence of any DNA lesion or ...
[26]
The influence of base pair tautomerism on single point mutations in ...
Oct 16, 2020 · The spontaneous mutations are exclusively a consequence of the proton transfer mechanisms shown in figure 2 (all other possible mutation ...
[27]
Recognition of Watson-Crick base pairs: constraints and limits due ...
Apr 1, 2014 · The natural bases of nucleic acids have a strong preference for one tautomer form, guaranteeing fidelity in their hydrogen bonding potential.
[28]
Identification by UV resonance Raman spectroscopy of an imino ...
The tautomerism of nucleic acid bases is of great interest because of the putative role of their unfavored tautomers in substitution mutagenesis (1, 2).Results · Uvrr Spectra Of Hodcyt · The Minor Tautomer Of Hodcyt...Missing: nucleobases | Show results with:nucleobases<|control11|><|separator|>
[29]
Genes are DNA (Nucleic Acid)
The "amino" base for purines is adenine, which is 6‑aminopurine. This amino ... The major groove is wider than the minor groove in DNA (Fig. 2.14d) ...
[30]
PCR-based development of DNA substrates containing modified ...
The interaction of most proteins with DNA occurs within the major groove. This not only offers greater accessibility than the minor groove but also displays a ...Materials And Methods · Dnase I Footprinting · Figure 5
[31]
Inversing the natural hydrogen bonding rule to selectively amplify ...
The third hydrogen bond helps understand why GC-rich DNA melts at higher temperatures compared to AT-rich DNA.
[32]
Biopolymers Problems
G-C base pairs have 3 hydrogen bonds, while A-T base pairs have two. Therefore, double-stranded DNA with a higher number of G-C base pairs ... higher melting ...
[33]
8-oxoguanine and 8-oxodeoxyguanosine Biomarkers of Oxidative ...
Mar 1, 2022 · Life style and urinary 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage: Effects of exercise, working conditions, meat intake, body ...
[34]
Guanine base stacking in G-quadruplex nucleic acids - PMC
Dec 24, 2012 · In this study, we investigate how guanine base stacking influences the stability of G-quadruplexes and their stacked higher-order structures.
[35]
Stacking free energies of all DNA and RNA nucleoside pairs and ...
For both DNA and RNA it can be seen that the most favorable ΔGstack values are associated with either an adenine or a guanine (i.e. a purine) at the 5′ ...
[36]
[PDF] Nucleotides and Nucleic Acids - Rose-Hulman
Nucleotides form parts of some cofactors, including NAD, FAD, and coenzyme ... most commonly used base are the purines adenine and guanine, the pyrimidines.
[37]
GTP before ATP: The energy currency at the origin of genes - PMC
GTP was the ancestral energy currency of protein synthesis. The use of GTP in translation and ATP in small molecule synthesis are conserved across all lineages.
[38]
[PDF] Nucleo'de)Metabolism) (Chapter)23) - Kansas State University
NitrogenBContaining)Heterocyclic)Bases). • There(are(two(classes(of(aromatic(amine(structures(used( for(the(bases:(purines(and(pyrimidines.(. (. – There(are ...
[39]
Uracil | C4H4N2O2 | CID 1174 - PubChem - NIH
Uracil is a common and naturally occurring pyrimidine nucleobase in which the pyrimidine ring is substituted with two oxo groups at positions 2 and 4.
[40]
Cytosine deamination and the precipitous decline of spontaneous ...
Jul 5, 2016 · The hydrolytic deamination of cytosine and 5-methylcytosine residues in DNA appears to contribute significantly to the appearance of spontaneous mutations.Abstract · Sign Up For Pnas Alerts · Results
[41]
Detection of UV-Induced Thymine Dimers - PubMed
Ultraviolet rays induce interstrand and intrastrand DNA cross-links, usually thymine-thymine cyclobutane dimer (T-T) and thymine-thymine pyrimidine-pyrimidone ( ...
[42]
Crystal structure of Escherichia coli uracil DNA glycosylase and its ...
The DNA repair enzyme uracil DNA glycosylase (UDG) catalyzes the hydrolysis of premutagenic uracil residues from single-stranded or duplex DNA, producing ...
[43]
Occurrence, Properties, Applications and Analytics of Cytosine and ...
Sep 3, 2025 · 3.3. Solubility and Physical Properties. Cytosine, as a pyrimidine base, is a moderately polar compound [34]. One molecule contains three ...
[44]
Epigenetic mechanisms in mammals - PMC - PubMed Central - NIH
In the mammalian genome DNA methylation occurs by covalent modification of the fifth carbon (C5) in the cytosine base and the majority of these modifications ...
[45]
Epigenetic regulatory functions of DNA modifications
Jul 21, 2015 · We present the symmetric modification of 5-methylcytosine on CpG dinucleotide as a key feature, because it permits the inheritance of methylation patterns ...
[46]
8-Oxoguanine: from oxidative damage to epigenetic and ... - Nature
Oct 21, 2022 · 8-oxoguanine in DNA (8-oxo-dG) induces a G > T (C > A) mutation in cancers, which can be deleterious and thus actively repaired by DNA repair pathways.
[47]
Stabilization of RNA stacking by pseudouridine - Oxford Academic
Pseudouridine forms a more stable base stacking arrangement than uridine, an effect that is propagated throughout the helix to stabilize stacking of ...
[48]
Interplay between N6-adenosine RNA methylation and mRNA splicing
Altered levels of N6-methyladenosine regulators regulate splicing. Proteins that deposit or remove m6A on pre-mRNAs are involved in splicing control. Several ...
[49]
m6A: Signaling for mRNA splicing - PMC - NIH
Jun 28, 2016 · FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res 2014; 24:1403-19; PMID ...
[50]
Loss of a Conserved 7-methylguanosine Modification in 16S rRNA ...
Loss of a Conserved 7-methylguanosine Modification in 16S rRNA Confers Low-Level Streptomycin Resistance in Bacteria · Abstract · Publication types · MeSH terms.
[51]
Impact of queuosine modification of endogenous E. coli tRNAs on ...
One suggested purpose of queuosine modification is to reduce the preference of tRNAs with guanosine (G) at position 34 of the anticodon for decoding cytosine (C) ...
[52]
Queuosine tRNA Modification: Connecting the Microbiome to ... - NIH
Nov 26, 2024 · Queuine is driven from gut bacteria (and diet), then it is imported, via yet to be identified importers, and incorporated to transfer RNA (tRNA) ...
[53]
Biosynthesis of wyosine derivatives in tRNAPhe of Archaea
The presence of tricyclic wyosine derivatives 3′-adjacent to anticodon is a hallmark of tRNAPhe in eukaryotes and archaea. In yeast, formation of wybutosine (yW) ...
[54]
Base Excision Repair of Oxidative DNA Damage - PMC - NIH
Base excision repair plays an important role in preventing mutations associated with the common product of oxidative damage, 8-oxoguanine.
[55]
Repair of deaminated bases in DNA - ScienceDirect.com
Base excision repair (BER) is the main mechanism by which cells correct various types of damaged DNA bases generated either by endogenous or exogenous factors.
[56]
Unnatural base pair systems for DNA/RNA-based biotechnology
In the late 1980s, Benner and colleagues first developed several unnatural base pairs, such as isoguanine–isocytosine (isoG–isoC) (Figure 2a) and xanthosine–5- ...
[57]
Enzymatic incorporation of a third nucleobase pair - Oxford Academic
12 nucleobases forming six base pairs joined by mutually exclusive hydrogen bonding patterns are readily available within that geometry.Materials And Methods · Extension Of Primers With... · Results
[58]
2-Aminopurine fluorescence quenching and lifetimes: Role of base ...
2-Aminopurine (2AP) is a fluorescent analog of guanosine and adenosine and has been used to probe nucleic acid structure and dynamics.
[59]
The applications of universal DNA base analogues - Oxford Academic
Abstract. A universal base analogue forms 'base pairs' with each of the natural DNA/RNA bases with little discrimination between them.
[60]
Reconstructive Methodology in the Synthesis of 2-Aminopurine - MDPI
Traube synthesis is a classic method to obtain purines through the annulation of the imidazole fragment into ortho-diaminopyrimidines [20]. This method was not ...Missing: variants artificial<|separator|>
[61]
[PDF] Molecular Design of Unnatural Base Pairs of DNA - TCI Chemicals
Hydrophilic unnatural base pairs by Benner's group. In the late 1980s, Steven Benner and his colleagues reported four types of unnatural base pairs bearing ...
[62]
Enzymic Reactions in the Synthesis of the Purines - Buchanan - 1959
The de novo Synthesis of Inosinic Acid in vitro. The Mechanism of Formation of Carbon-to-Nitrogen Bonds in Certain Reactions of Purine Synthesis. Summary ...Missing: seminal biosynthesis
[63]
Pathway Engineered Enzymatic de novo Purine Nucleotide Synthesis
The well-established metabolic pathway for de novo purine biosynthesis is outlined in Figure 1a,b. Enzymes of the pentose phosphate pathway convert glucose ...Missing: seminal papers
[64]
CAD, A Multienzymatic Protein at the Head of de Novo Pyrimidine ...
CAD is a 1.5 MDa particle with enzymatic activities for the first three steps in pyrimidine biosynthesis, unique to animals.
[65]
Pyrimidine Biosynthetic Enzyme CAD: Its Function, Regulation, and ...
The de novo biosynthesis of pyrimidine nucleotides provides essential precursors for multiple growth-related events in higher eukaryotes [30,31,32].
[66]
Lesch-Nyhan Syndrome - StatPearls - NCBI Bookshelf - NIH
Apr 24, 2023 · Lesch Nyhan syndrome is an inborn disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme, an enzyme of purine salvage ...Missing: nucleobase | Show results with:nucleobase
[67]
Human de novo purine biosynthesis - PubMed - NIH
Nov 12, 2020 · The focus of this review is the human de novo purine biosynthetic pathway. The pathway enzymes are enumerated, as well as the reactions they catalyze and their ...Missing: seminal paper Buchanan
[68]
A journey into the regulatory secrets of the de novo purine ... - Frontiers
Feb 19, 2024 · De novo purine nucleotide biosynthesis (DNPNB) consists of sequential reactions that are majorly conserved in living organisms.Missing: seminal | Show results with:seminal
[69]
(PDF) Purine and pyrimidine nucleotide metabolism in higher plants
Aug 10, 2025 · In this article the biosynthesis, interconversion and degradation of purine and pyrimidine nucleotides in higher plants are reviewed.
[70]
Surveying purine biosynthesis across the domains of life unveils ...
Aug 4, 2020 · In the Bacteria, a major differentiating feature of de novo purine biosynthesis is the increasing prevalence of gene fusions, where two or more ...Missing: seminal | Show results with:seminal
[71]
Formation of nucleobases in a Miller–Urey reducing atmosphere
Apr 10, 2017 · The study shows that Miller–Urey experiments produce RNA nucleobases in discharges and laser-driven plasma impact simulations carried out in a simple prototype ...
[72]
Prebiotic ribose synthesis: a critical analysis - PubMed
The formose reaction is the main cited method for prebiotic ribose synthesis, but evidence suggests ribose was unlikely available on prebiotic earth, except ...
[73]
Synthesis of purines under possible primitive earth conditions. I ...
Adenine has been synthesized in substatial amounts by heating a solution of hydrogen cyanide (1 to 15 M) in aqueous ammonia for one or several days at moderate ...
[74]
One‐Step Synthesis of Hypoxanthine from Glycinamide and ...
Guanine, Adenine, and Hypoxanthine Production in UV‐Irradiated Formamide Solutions: Relaxation of the Requirements for Prebiotic Purine Nucleobase Formation.
[75]
Synthesis of activated pyrimidine ribonucleotides in prebiotically ...
May 14, 2009 · Powner, M. W. et al. On the prebiotic synthesis of ribonucleotides: photoanomerisation of cytosine nucleosides and nucleotides revisited.
[76]
Prebiotic chemistry: a review of nucleoside phosphorylation and ...
Jan 11, 2023 · Montmorillonite, a clay mineral, is also a relatively effective catalyst [111–116] for oligomer formation even with dilute solutions of ...Missing: 2020s | Show results with:2020s
[77]
The difficult case of an RNA-only origin of life - PMC - PubMed Central
Aug 28, 2019 · The RNA world hypothesis is probably the most extensively studied model for the emergence of life on Earth.