Nucleotide Chemistry: Structure and Bases

Nucleotide Chemistry Overview

• Purine and pyrimidine bases along with their derivatives such as nucleosides and nucleotides are the components which make up nucleic acids.
• There are two main types of nucleic acids: Deoxyribonucleic acid (DNA) and Ribonucleic acid (RNA).
• The building block of nucleic acids is the nucleotide consisting of a nitrogenous base (purine or pyrimidine), a pentose sugar (ribose or deoxyribose), and a phosphate group.

Structural Breakdown

• 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

• Nitrogenous bases are heterocyclic ring compounds containing carbon and nitrogen atoms.
• There are two classes of nitrogenous bases based on their abundance in cells, which are major and minor bases.

Major Bases

• 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 (present only in DNA), and Uracil (present only in RNA).

Minor Bases

• Present in trace amounts, often methylated, like 5-methyl cytosine and N7-methylguanine.
• Minor bases serve important functions such as oligonucleotide recognition, regulation of the half-life of RNAs, and protecting host DNA from digestion by DNAses.
• Xanthine, hypoxanthine, and uric acid exist as bases in a free state inside cells.
• 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 Details

• Nucleosides consist of a base and a sugar (either ribose or deoxyribose).
• Sugars bind 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.
• Numbering of the sugar atoms includes a prime symbol to differentiate sugar atoms from those of the base.

Nucleotides Details

• Nucleotides consist of a base, a sugar, and a 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) or enol (lactim) form, and amino (-NH2) or imino (=NH) form.
• Tautomerism describes the change from one form to the other.
• The keto and amino forms are common at physiological pH.

Syn and Anti-Conformers

• Nucleotides exist as stable, non-interconvertible syn and anti-conformers.
• The β-N-glycosidic bond is a rigid bond with limited rotation, interconversion between conformers requires bond rupture and reformation.
• The anti-conformer is the predominant form.

Nomenclature of Bases, Nucleosides, and Nucleotides

• Adenine (A) becomes Adenosine as a nucleoside, and Adenosine monophosphate (AMP) as a nucleotide.
• Guanine (G) becomes Guanosine as a nucleoside, and Guanosine monophosphate (GMP) as a nucleotide.
• Xanthine (X) becomes Xanthosine as a nucleoside, and Xanthosine monophosphate (XMP) as a nucleotide.
• Hypoxanthine (I) becomes Inosine as a nucleoside, and Inosine monophosphate (IMP) as a nucleotide.
• Cytosine (C) becomes Cytidine as a nucleoside, and Cytidine monophosphate (CMP) as a nucleotide.
• Uracil (U) becomes Uridine as a nucleoside, and Uridine monophosphate (UMP) as a nucleotide.
• Thymine (T) becomes Thymidine as a nucleoside, and Thymidine monophosphate (TMP) as a nucleotide.

Functions of Nucleotides

• Both purine and pyrimidine nucleotides are essential for the structure of nucleic acids like DNA and RNA.
• Purine Nucleotides:
• Act as high-energy stores in the form of ATP and GTP.
• c-AMP and c-GMP function as second messengers for hormones.
• Integral to the structure of coenzymes such as NAD, NADP, FAD, and FMN, which serve as hydrogen carriers, and COASH, which acts as an acid carrier.
• Pyrimidine Nucleotides:
• Are part of high-energy intermediates like UDP-glucose, important in glycogenesis and the uronic acid pathway.
• Serve as high-energy stores in the form of CTP and UTP.
• Active in the structure of high energy intermediates: Uridine diphosphate glucose (UDP-glucose) used in glycogenesis and uronic acid pathway.
• Are active methyl donors, (S-adenosyl methionine, SAM).
• Are active sulfate donors, (3'phosphoadenosine-5'-phosphosulfate, PAPS).
• Serve regulatory functions: An example is ADP levels which regulate the rate of oxidative phosphorylation in mitochondria.

Explore the chemistry of nucleotides, the building blocks of nucleic acids like DNA and RNA. Learn about the components of nucleotides, including nitrogenous bases (purines and pyrimidines), pentose sugars, and phosphate groups. Understand the structural differences between nucleosides and nucleotides.