Nucleotide Chemistry: Bases, DNA, and RNA

Nucleotide Chemistry

• Purine and pyrimidine bases, along with their derivatives, form the building blocks of nucleic acids as nucleosides and nucleotides.
• There are two primary types of nucleic acids: Deoxyribonucleic acid (DNA) and Ribonucleic acid (RNA).
• Nucleotides, the building blocks of nucleic acids, consist of a nitrogenous base(purine or pyrimidine), a pentose sugar (ribose or deoxyribose), and a phosphate group.

Nitrogenous Bases

• They are heterocyclic ring compounds containing carbon and nitrogen.
• The two classes of nitrogenous bases are based on abundance within the cell: major bases and minor bases.
• Major bases are abundant and include purines and pyrimidines.
• Purines, such as adenine and guanine, are found in both DNA and RNA.
• Pyrimidines include cytosine, which is present in both DNA and RNA; thymine, found only in DNA; and uracil, present only in RNA.

Minor Bases

• Minor bases are present in trace amounts and are typically methylated, such as 5-methyl cytosine and N7-methylguanine.
• Minor bases serve important functions, including 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, including xanthine, hypoxanthine, and uric acid.
• Methylated xanthines include caffeine (1,3,7 trimethyl xanthine) in coffee, theophylline (1,3 dimethyl xanthine) in tea, and theobromine (3,7 dimethyl xanthine) in coca.

Nucleosides

• They consist of a base and a sugar (either ribose or deoxyribose).
• Sugars attach to bases via a covalent, β-N-glycosidic bond, linking the C₁ of the sugar with N-9 of a purine or N-1 of a pyrimidine.
• A prime notation (e.g., 3 or 5) helps to distinguish atoms in the sugar from those in the base.

Nucleotides

• They are composed of a base, sugar, and phosphate group.
• The phosphate group attaches to the C-5 position of the sugar.

Tautomerism

• Purines exist in two isoforms: keto (or lactam) and enol (or lactim) forms, as well as amino (-NH2) and imino (=NH) forms.
• Tautomerism refers to the change from one form to another.
• Keto and amino forms are prevalent under physiological pH conditions.

Syn and Anti-Conformers

• Nucleotides exist in stable, non-interconvertible syn and anti conformations.
• The β-N-glycosidic bond forms a firm bond that restricts rotation.
• Conversion from one conformer to another requires the rupture and reformation of the glycosidic bond
• The anti-conformer is the predominant form.

Functions of Nucleotides

• Both purine and pyrimidine nucleotides are elemental in the construction of nucleic acids like DNA and RNA.
• Purine nucleotides are essential for high-energy storage molecules such as ATP and GTP.
• As intracellular signals cAMP and cGMP act as secondary messengers for many hormones.
• They form the base of many coenzymes like NAD, NADP, FAD, and FMN, involved in hydrogen transfer, and COASH, which is involved in acid transfer.
• They act as the active methyl donor (S-adenosyl methionine, or SAM).
• They act as the active sulfate donor (3'phosphoadenosine-5'-phosphosulfate, or PAPS).
• Nucleotides such as ADP regulate rates of oxidative phosphorylation in the mitochondria.
• Pyrimidine nucleotides participate in the formation of high-energy intermediates: -Uridine diphosphate glucose (UDP-glucose), is crucial in glycogenesis and the uronic acid pathway.
• Pyrimidine nucleotides are also involved in high-energy storage as CTP and UTP.

Learn about nucleotide chemistry, including purine and pyrimidine bases, DNA, and RNA. Nucleotides consist of a nitrogenous base, a pentose sugar, and a phosphate group. Explore major and minor bases, including adenine, guanine, cytosine, thymine, and uracil.