BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 9. NUCLEIC ACIDS

9.3. Physicochemical Properties of Nitrogenous Bases

Nitrogenous bases are characterized by the existence of tautomeric forms, a type of isomerism in which isomers can interconvert (Fig. 9.1).

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Fig. 9.1. Tautomers of nitrogenous bases

Tautomerism is based on proton migration, which involves intramolecular shifts of a hydrogen Nucleus from one atom to another. Such migration is usually accompanied by Changes in the electronic Structure OF THE molecule. Depending on The structure of the heterocycle, nitrogenous bases that make up Nucleic Acids are capable of amino-imino and keto-enol (lactam-lactim) tautomerism.

Within nucleic acids, adenine and cytosine exist predominantly in the amino form, whereas guanine, thymine, and uracil occur in the lactam form.

Nitrogenous bases are sparingly soluble in Water. At neutral pH, guanine exhibits the lowest solubility.

Due to their heterocyclic aromatic nature, purine and pyrimidine nitrogenous bases absorb electromagnetic energy in the ultraviolet range (200-300 nm), with an absorption maximum of approximately 260 nm. This property is utilized for the Quantitative determination of nucleic acids.

Nucleosides are N- or C-glycosidic derivatives of purine or pyrimidine nitrogenous bases. Nucleosides contain ribose or deoxyribose in the furanose form, which are always D-isomers and β-anomers.

The numbering of atoms in the carbohydrate residue remains the same as in free pentoses, starting from the glycosidic center. However, to distinguish them from the atom numbers of the nitrogenous bases, they are designated with primes: the carbon atom linked to the heterocycle is numbered as 1'-, the carbon atoms with hydroxyl groups in ribonucleotides as 2'-, 3'-, and 5'-, while DNA components, i.e., deoxyribonucleosides, contain hydroxyl groups at the 3'- and 5'-positions.

The carbohydrate residue and the nitrogenous base are linked by a relatively acid-labile N-glycosidic bond between the first carbon atom of the pentose and the first nitrogen atom of the pyrimidine or the ninth nitrogen atom of the purine. Depending on the type of pentose, two MAIN TYPES OF nucleosides are distinguished: ribonucleosides (containing ribose and found in RNA) and deoxyribonucleosides (containing deoxyribose and found in DNA). The structures of two nucleosides are shown as an example:

Theoretically, the pentose residue and nitrogenous bases in nucleosides are capable of free rotation around the axis of the glycosidic bond; however, Steric hindrances actually prevent this. A necessary condition for the complementary interaction of purine and pyrimidine bases in the double-stranded DNA molecule is the anti-conformation of the molecules, which is more energetically favorable for natural nucleosides than the syn-conformation (Fig. 9.2).

Fig. 9.2. Structure of the syn- (A) and anti- (B) configurations of guanosine

Nucleosides lack reducing properties, as evidenced by the absence of a free aldehyde group in the carbohydrate component. Nucleosides are significantly more soluble in water than their parent nitrogenous bases. Furthermore, they are quite stable in neutral and alkaline environments and undergo Hydrolysis in the presence of mineral and organic acids. The rate of hydrolysis depends on the hydrogen ion concentration. Purine nucleosides are less resistant to hydrolysis than pyrimidine ones.

NUCLEOTIDES are phosphoric acid esters of nucleosides in which phosphoric acid is linked by an ester bond to one of the free hydroxyl groups of the pentose. All nucleotides are strong acids because the phosphoric acid residue readily dissociates. The monomeric units of RNA, in which the carbohydrate moiety is D-ribose, are called ribonucleotides, whereas the monomeric units of DNA, containing D-deoxyribose, are termed deoxyribonucleosides. In ribonucleotides, the phosphate group can attach at the 2', 3', or 5' positions of D-ribose, while in deoxyribonucleosides, it attaches at the 3' and 5' positions of D-deoxyribose. At the same time, As a result of enzymatic synthesis or degradation reactions of nucleic acids, all Cells contain only nucleoside-5-phosphates in free form.

Phosphorylation of nucleoside monophosphates (NMPs) at the C-5' carbon atom of the pentose leads to The formation of nucleoside diphosphates (NDPs) and nucleoside triphosphates (NTPs). The structures of ATP, as well as the corresponding di- and monophosphates, are given as an example (Fig. 9.3).

Fig. 9.3. Structure of adenosine mono-, di-, and triphosphates

All nucleoside phosphates exist in The Cell as anions; therefore, adenosine phosphates are more correctly designated as AMP^2-, ADP^3-, and ATP^4-. Nucleotides are most commonly named after their corresponding nucleosides, indicating the attachment site of the orthophosphate to the ribose or deoxyribose residue. In addition, somewhat shortened or abbreviated names are also used. Table 9.2 presents the nomenclature of Nucleosides and Nucleotides.

Table 9.2

Nomenclature of nitrogenous bases, nucleosides, and nucleotides

Along with the major components that make up nucleic acids, minor nucleotides (from Lat. minor – smaller) are occasionally found. They are particularly diverse in tRNA. Minor nucleotides are formed in the body as a result of chemical transformations (covalent modifications) of nucleotide residues that occur after the polynucleotide chain has already been formed. For example, uridine residues in certain Regions of the RNA precursor can undergo hydrogenation, leading to the formation of a dihydrouridine residue, sulfhydration to form a thiouridine residue, or isomerization, which results in the formation of a pseudouridine residue (Ψ) where ribose is attached to uracil at the fifth position via a C-glycosidic bond:

Methylated derivatives of nitrogenous bases are extremely widespread in RNA (as well as in DNA). Furthermore, in RNA, the 2'-OH groups of ribose residues can also serve as targets for methylation. Below are the structures of various minor nucleotides found in nucleic acid molecules:

Nucleotide derivatives, particularly adenosines, include S-adenosylmethionine, the active form of The amino acid Methionine. In this compound, the sulfonium structure with a trisubstituted sulfur atom (=S⁺-CH₃) is unstable, which accounts for the high reactivity of the methyl group. Acting as a methyl group donor in biomolecule methylation reactions, S-adenosylmethionine participates in the synthesis of creatine, The conversion of the amino alcohol ethanolamine into Choline, noradrenaline into adrenaline, and the methylation of nitrogenous bases in nucleotides, among other processes.

Deoxyribonucleotides in the body are used exclusively for DNA Biosynthesis, whereas ribonucleotides perform a variety of Functions:

✵ they serve as precursors for RNA biosynthesis;

✵ all nucleoside triphosphates are high-energy (macroergic) compounds whose chemical energy is utilized by the Organism for the synthesis of biological substances; ATP plays a unique role in energy transformations, for example:

amino acid + tRNA + ATP → aminoacyl-tRNA + AMP + PP_i; fatty acid + CoA-SH + ATP → acyl-CoA + AMP + PP_i; nicotinamide mononucleotide + ATP → NAD + PP_i; nicotinamide adenine dinucleotide + ATP → NADP + ADP;

✵ nucleotide derivatives act as Donors of active substrates in the synthesis of homo- and Heteropolysaccharides, Lipids, and Proteins. For instance, GDP-mannose participates in the synthesis of Glycogen and glycosaminoglycans, while CDP-choline is involved in phospholipid synthesis;

Fig. 9.4. Coenzymes containing adenosine in their structure

✵ S-adenosylmethionine (SAM), 3'-phosphoadenosine-5'-phosphosulfate (PAPS), and UDP-glucuronic acid are involved in the universal detoxification system that ensures the elimination of foreign substances (xenobiotics) and certain endogenous metabolites from the body;

✵ adenylic ribonucleotides (AMP) are components of coenzymes such as NAD, NADP, FAD (FMN), and coenzyme A (CoA), which participate in numerous enzymatic reactions. The structures of these coenzymes are shown in Fig. 9.4.

✵ a distinct group is formed by Cyclic Nucleotides, in which the phosphate residue forms ester bonds with the 3'- and 5'-hydroxyl groups of ribose. In the organism, they act as intracellular (secondary) messengers in signal Transduction from Hormones, growth factors, Neurotransmitters, or other extracellular regulators: