Nucleotide vs Nucleoside: Difference and Comparison

What is the Nucleoside?

Nucleosides molecules in biochemistry are the basic compounds containing a base that is nitrogenous and five carbon sugar (ribose or deoxyribose). The nitrogenous base may be adenine, guanine, cytosine, thymine (in DNA) or uracil (in RNA). These are some of the basic molecules necessary to make nucleotides, which in turn serve as monomers for all types of small and large ribonucleic acids. The nitrogenous base and pentose sugar is whats makes up a nucleoside. They are necessary for generating nucleotides, which contribute to the formation of both DNA and RNA strands. They are crucial intermediates for the storage and transfer of genetic information in replication, transcription and translation.

Structure of Nucleoside

A nucleoside is a fundamental molecular unit composed of two main components: a nitrogenous base and a pentose sugar. The way these components are linked would be glycosidic bond.

Understanding the structure of nucleosides is fundamental to comprehending their role in genetic information storage and transmission in biological systems.

What are Nucleoside Analogs?

Nucleoside analogs are synthetic compounds that mimic the structure of natural nucleosides but contain modifications to their chemical structure. These modifications can alter their function and interactions within biological systems. Nucleoside analogs typically have alterations in their nitrogenous base structure. These modifications can involve substitutions or additions of functional groups to the base ring. Modifications can also occur in the sugar component of nucleoside analogs. These alterations may involve changes to the pentose sugar structure, such as deoxygenation or modification of hydroxyl groups. Many nucleoside analogs function as antimetabolites, disrupting nucleic acid synthesis by interfering with DNA replication or RNA transcription. Nucleoside analogs are valuable tools in biochemical and pharmaceutical research. They help elucidate biological processes by selectively inhibiting or modifying nucleic acid metabolism. Nucleoside analogs represent a diverse class of compounds with significant therapeutic and research applications. Their ability to mimic natural nucleosides while exerting specific effects on nucleic acid metabolism makes them valuable tools in medicine and molecular biology.

What are Nucleoside Reverse Transcriptase Inhibitors (NRTIs)?

Nucleoside reverse transcriptase inhibitors (NRTIs) are a class of antiretroviral drugs used primarily in the treatment of HIV/AIDS. They work by inhibiting the activity of the enzyme reverse transcriptase, which is crucial for the replication of the HIV virus. By interfering with viral replication through inhibition of reverse transcriptase, they help control viral load, preserve immune function, and improve quality of life for individuals living with HIV. Ongoing research focuses on developing new NRTIs with improved efficacy, reduced toxicity, and resistance profiles to combat the challenges posed by HIV infection. Reverse transcriptase is an enzyme responsible for converting the viral RNA of HIV into DNA, which is then integrated into the host cell's genome. NRTIs act as nucleoside analogs that mimic natural nucleosides and are incorporated into the viral DNA during replication. Once incorporated into the growing viral DNA chain, NRTIs lack a 3'-hydroxyl group necessary for further DNA elongation. This results in premature termination of the DNA chain synthesis, preventing the completion of viral replication.

What is a Nucleotide?

A nucleotide is a fundamental building block of nucleic acids, which include DNA and RNA. It consists of three main components: a nitrogenous base, a pentose sugar (either ribose in RNA or deoxyribose in DNA), and a phosphate group. Nucleotides are essential molecules that play crucial roles in genetic information storage, energy transfer, and cellular signaling. Their structure and composition vary between DNA and RNA but share the fundamental components of a nitrogenous base, pentose sugar, and phosphate group. Understanding nucleotides is fundamental to grasping the mechanisms of inheritance, molecular biology, and biochemistry.

Structure of Nucleotide

The structure of a nucleotide involves a nitrogenous base (adenine, guanine, cytosine, thymine, or uracil), attached to the C1' carbon of the sugar molecule, with a phosphate group linked to the C5' carbon of the sugar. This structure forms the backbone of DNA and RNA strands.

The nitrogenous base can be one of two types: purines (adenine (A) and guanine (G)) or pyrimidines (cytosine (C), thymine (T) in DNA, or uracil (U) in RNA). Purines are larger double-ring structures, while pyrimidines are smaller single-ring structures.

In DNA, the pentose sugar is deoxyribose, which lacks an oxygen atom on the 2' carbon compared to ribose. In RNA, the pentose sugar is ribose, which has an additional hydroxyl group on the 2' carbon.

The phosphate group is attached to the 5' carbon of the pentose sugar through a phosphoester bond. It can be mono-, di-, or triphosphate, depending on the number of phosphate groups attached.

What is a Single Nucleotide Polymorphism (SNP)?

A Single Nucleotide Polymorphism (SNP) is a variation at a single position in a DNA sequence among individuals. SNPs are the most common type of genetic variation among people and can be found throughout the genome. They occur approximately once in every 300 nucleotides, which means there are roughly 10 million SNPs in the human genome. SNPs involve the substitution of one nucleotide for another. For example, a cytosine (C) may be replaced by a thymine (T) at a specific position in the DNA sequence. They serve as crucial tools in genetic research, personalized medicine, and understanding human evolution and diversity. By studying SNPs, scientists and healthcare providers can gain insights into genetic predispositions, optimize therapeutic strategies, and advance the field of genomics.

Difference between Nucleotide and Nucleoside

Nucleotides and nucleosides are both fundamental components of nucleic acids but differ in their structures and roles. A nucleoside consists of a nitrogenous base (either a purine or pyrimidine) attached to a five-carbon sugar (ribose in RNA or deoxyribose in DNA). In contrast, a nucleotide is a nucleoside with one or more phosphate groups attached to the 5' carbon of the sugar. This additional phosphate group enables nucleotides to play critical roles in cellular processes, such as energy transfer (e.g., ATP), signaling (e.g., cAMP), and as building blocks of DNA and RNA. Nucleosides, lacking the phosphate group, do not participate directly in these processes but can be converted into nucleotides within the cell.

Components of Nucleotide and Nucleoside

Phosphate Group of Nucleotide and Nucleoside

Functionality in Biological Processes of Nucleotide and Nucleoside

Formation of Nucleotide and Nucleoside

Applications of Nucleoside and Nucleotide

Nucleosides and nucleotides are crucial to numerous biological processes and have broad applications in medicine, biotechnology, and research. Their roles extend from fundamental cellular functions to advanced therapeutic and diagnostic tools.

DNA and RNA Synthesis

Nucleotides are the building blocks of DNA and RNA, essential for the synthesis of genetic material. DNA polymerases and RNA polymerases incorporate nucleotides into growing nucleic acid chains during replication and transcription.

PCR and Sequencing

Nucleotides are fundamental in Polymerase Chain Reaction (PCR) and sequencing technologies. They provide the necessary components for amplifying and sequencing DNA, which are critical techniques in molecular biology, diagnostics, and forensic science.

Gene Editing

Techniques like CRISPR-Cas9 rely on nucleotides for gene editing. Guide RNAs(gRNA), which are composed of nucleotides, direct the Cas9 enzyme to specific genomic locations for precise modifications.

Molecular Probes and Diagnostics

Labeled nucleotides are used as probes in various diagnostic techniques, including fluorescence in situ hybridization (FISH) and microarray assays. These probes help detect specific nucleic acid sequences, aiding in disease diagnosis and genetic research.

RNA Interference (RNAi)

Synthetic nucleotides are employed in RNA interference techniques to silence specific genes. Small interfering RNAs (siRNAs) and microRNAs (miRNAs) are used to downregulate the expression of target genes, providing powerful tools for studying gene function and developing gene therapies.

Therapeutic Applications

Nucleotides and nucleosides serve as scaffolds for designing new therapeutic agents. Modifications to these molecules can enhance their efficacy, specificity, and pharmacokinetic properties, leading to the development of novel drugs for various diseases, such as HIV, cancer and viral infections.

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Hot Spots of Nucleoside and Nucleotide Research

Research into nucleosides and nucleotides is advancing rapidly, driven by their essential roles in biology and promising applications in medicine.

Schematic diagram of nucleoside and nucleotide analogues.General structure of nucleoside and nucleotide analogs. (Mahmoud, S.S.; et al, 2018)

Personalized Medicine and Genomics

SNPs and GWAS: Single Nucleotide Polymorphisms (SNPs) are pivotal in personalized medicine, guiding treatment decisions based on individual genetic variations identified through Genome-Wide Association Studies (GWAS).

Antiviral and Anticancer Drug Development

Analog Development: Ongoing efforts focus on developing new nucleoside and nucleotide analogs to combat viral infections and cancer. These analogs enhance drug efficacy while minimizing adverse effects and overcoming resistance mechanisms.

Gene Therapy and Genetic Engineering

CRISPR-Cas9 and Beyond: Advancements in gene editing technologies, particularly CRISPR-Cas9, are revolutionizing genetic therapies by enabling precise modifications to correct genetic mutations. Emerging techniques like base editing offer even greater precision in genetic engineering.

Synthetic Biology and Biotechnology

Synthetic Nucleotides: Synthetic biology leverages synthetic nucleotides to construct artificial genetic circuits and novel biological systems. Efforts to expand the genetic alphabet aim to create organisms with enhanced functionalities.

Reference

  1. Mahmoud, S.S.; et al. Antiviral Nucleoside and Nucleotide Analogs: A Review. Journal of Advanced Pharmacy Research. 2018, 2(2): 73-88.
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