Nucleotide Chemistry: Purines, Pyrimidines, Nucleic Acids

Nucleotide Chemistry Overview

• Purine and pyrimidine bases, their nucleosides, and nucleotides are 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, the nucleotide consists of a nitrogenous base (purine or pyrimidine), a pentose sugar (ribose or deoxyribose), and a phosphate group.

Components of Nucleic Acids

• Nucleotides are composed of a nucleoside and a phosphate group
• Nucleosides are composed of a nitrogenous base (purine or pyrimidine) and a pentose sugar (ribose or deoxyribose).

Nitrogenous Bases: Purines and Pyrimidines

• Nitrogenous bases consist of heterocyclic ring compounds, with carbon and nitrogen.
• Two classes exist based on abundance in cells: major bases and minor bases.
• Major bases are present in large amounts.
  • Purines include adenine and guanine, found in both DNA and RNA.
  • Pyrimidines include cytosine (present in both DNA and RNA), thymine (DNA only), and uracil (RNA only).
• Minor bases are present in trace amounts and are usually methylated, such as 5-methyl cytosine and N7-methylguanine.
  • Minor bases have roles which include oligonucleotide recognition, regulation of RNA half-life, and protection of host DNA.

Free State Bases

• Bases can be present in a free state inside cells, like xanthine, hypoxanthine, and uric acid.
• Methylated xanthines include caffeine (in coffee), theophylline (in tea), and theobromine (in coca).

Nucleosides

• Nucleosides consist of a base and a sugar (ribose or deoxyribose).
• Sugars bind bases via a covalent, β-N-glycosidic bond, linking the C₁ of sugar with the N-9 of a purine or the N-1 of a pyrimidine.
• The numbering of the sugar atoms includes a prime (e.g., 3' or 5') to differentiate sugar atoms from those of the base.

Nucleotides

• Nucleotides consist of a base, sugar, and phosphate group.
• The phosphate is attached to the C-5 of the sugar.

Tautomerism

• Purines and pyrimidines exist in two isoforms: keto (or lactam) or enol (lactim) form, and amino (-NH₂) or imino (=NH) form.
• Tautomerism refers to the interchange/change process from one form to the other.
• At physiological pH, keto and amino forms are common.

Syn and Anti-Conformers

• Nucleotides are present as stable, non-interconvertible syn and anti conformers.
• Rotation isn't possible around the β-N-glycosidic bond and interconversion from one form to another only occurs through rupture and reformation of the glycosidic bond.
• The anti-conformer predominates.

Bases, Nucleosides, and Nucleotides Nomenclature

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

Functions of Nucleotides

• Both purine and pyrimidine nucleotides participate in the structure of nucleic acids like DNA and RNA.
• Purine nucleotides are in the structure of high-energy stores like ATP and GTP.
• Purines participate in intracellular signals: cAMP and cGMP act as second messengers for many hormones.
• Purines are in the structure of many coenzymes like NAD, NADP, FAD, and FMN, serving as hydrogen carriers, and COASH, serving as an acid carrier.
• Purines form the active methyl donor (S-adenosyl methionine, SAM).
• Purines form the active sulfate donor (3'phosphoadenosine-5'-phosphosulfate, PAPS).
• Purines have regulatory functions like ADP levels regulating the rate of oxidative phosphorylation in mitochondria.
• Pyrimidine nucleotides are in the structure of high-energy intermediates: Uridine diphosphate glucose (UDP-glucose) is used in glycogenesis and the uronic acid pathway.
• Pyrimidines form high-energy stores CTP and UTP.

Overview of nucleotide chemistry, focusing on purine and pyrimidine bases, nucleosides, nucleotides as building blocks of nucleic acids (DNA and RNA). Includes major and minor nitrogenous bases like adenine, guanine and cytosine.