Nucleotide Chemistry: Purines, Pyrimidines, DNA, and RNA

Nucleotide Chemistry Basics

• Purine and Pyrimidine bases, along with their nucleosides and nucleotides, form the building blocks of nucleic acids
• There are two main types of nucleic acids - Deoxyribonucleic acid (DNA) and Ribonucleic acid (RNA)
• The building unit of nucleic acid, i.e. the nucleotide, comprises a nitrogenous base (purine or pyrimidine), a pentose sugar (ribose or deoxyribose), and a phosphate group

Nitrogenous Bases

• These bases have a heterocyclic ring structure containing carbon and nitrogen
• There are major and minor bases according to their abundance in cells
• Major bases are present in large amounts
• Major purine bases: Adenine and guanine are found in both DNA and RNA
• Major pyrimidine bases include: Cytosine (present in both DNA and RNA), Thymine (present only in DNA), and Uracil (present only in RNA)

Minor Bases

• Minor bases are present in trace amounts and are usually methylated, such as 5-methyl cytosine and N7-methylguanine
• Minor bases have important functions involving Oligonucleotide recognition, Regulating the half-life of RNAs, and Protecting host DNA from digestion by DNAses
• Some bases exist in a free state inside cells: Xanthine, hypoxanthine, and uric acid
• Methylated xanthines: Caffeine (1, 3, 7 trimethyl xanthine) in coffee, theophylline (1, 3 dimethyl xanthine) in tea, and theobromine (3, 7 dimethyl xanthine) in coca

Nucleosides

• Nucleosides consist of a base and a sugar (ribose or deoxyribose)
• Sugars are bound to bases via a covalent, β-N-glycosidic bond which links the C₁ of the sugar with N-9 of a purine or N-1 of a pyrimidine
• Numbering of sugar atoms uses a prime to differentiate them from base atoms (e.g., 3' or 5')

Nucleotides

• A nucleotide consists of a base, sugar, and phosphate group
• The phosphate group is attached to the C-5 of the sugar

Tautomerism

• Purines and pyrimidines can exist in two isoforms: keto (or lactam) and enol (lactim) forms, as well as amino (-NH₂) and imino (=NH) forms
• Tautomerism occurs when a molecule changes from one form to another
• Keto and amino forms are common at the physiological pH

Syn and Anti-Conformers

• Nucleotides exist as stable, non-interconvertible syn and anti conformers
• The β-N-glycosidic bond is very stable, restricting rotation around the bond, where Interconversion between conformers requires rupture and reformation of the glycosidic bond
• The anti-conformer is the predominant form

Bases, Nucleosides, and Nucleotides Nomenclature

• Adenine (A) forms Adenosine and Adenosine monophosphate (AMP); Deoxyadenosine and Deoxyadenosine monophosphate (dAMP)
• Guanine (G) forms Guanosine and Guanosine monophosphate (GMP); Deoxyguanosine and Deoxyguanosine monophosphate (dGMP)
• Hypoxanthine (I) forms Inosine and Inosine monophosphate (IMP)
• Cytosine (C) forms Cytidine and Cytidine monophosphate (CMP); Deoxycytidine and Deoxycytidine monophosphate (dCMP)
• Uracil (U) forms Uridine and Uridine monophosphate (UMP)
• Thymine (T) forms Thymidine and Thymidine monophosphate (TMP)
• Xanthine (X) forms Xanthosine and Xanthosine monophosphate (XMP)

Functions of Nucleotides

• Both purine and pyrimidine nucleotides are building blocks of nucleic acids, DNA and RNA
• Purine nucleotides are high energy stores, ATP and GTP, and are intracellular signals like cAMP and cGMP which act as second messengers for many hormones
• Purine nucleotides enter form various coenzymes such as NAD, NADP, FAD, and FMN, which act as hydrogen carriers, and COASH, which acts as an acid carrier
• Purine nucleotides are the active methyl donor (S-adenosyl methionine, SAM), the active sulfate donor (3'phosphoadenosine-5'-phosphosulfate, PAPS), and regulate oxidative phosphorylation rate in mitochondria via ADP levels
• Pyrimidine nucleotides form high energy intermediates, for example, Uridine diphosphate glucose (UDP-glucose), used in glycogenesis and the uronic acid pathway
• Pyrimidine nucleotides serve as high energy stores: CTP and UTP

Explore the essentials of nucleotide chemistry. Learn about purine and pyrimidine bases, their nucleosides and nucleotides, and their role as building blocks of nucleic acids. Understand the differences between major and minor bases, including Adenine, Guanine, Cytosine, Thymine, and Uracil in DNA and RNA.