Rucete ✏ Lehninger Principles of Biochemistry In a Nutshell
8.1 Some Basic Definitions and Conventions
This chapter introduces the basic structural concepts and terminology for nucleotides and nucleic acids, which form the molecular basis of genetic information. DNA stores and transmits hereditary information, while RNA carries and expresses it through multiple specialized functions. Together, these molecules enable the flow of genetic information within all living systems.
DNA, RNA, and Genes
• A gene is a segment of DNA that contains the information necessary to synthesize a functional biological product, either a protein or an RNA.
• DNA’s sole function is to store and transmit biological information across generations.
• RNA molecules perform broader roles, including catalysis and regulation, with several distinct types:
– rRNA: structural and catalytic component of ribosomes.
– mRNA: intermediary that carries genetic information from DNA to ribosomes.
– tRNA: adapter molecule translating mRNA codons into specific amino acids.
– ncRNA: noncoding RNAs with regulatory, structural, or enzymatic functions.
Structure of Nucleotides and Nucleic Acids
• Each nucleotide consists of three parts: a nitrogenous base, a pentose sugar, and one or more phosphate groups.
• The molecule without phosphate is a nucleoside.
• The nitrogenous bases derive from two parent compounds: purine (adenine, guanine) and pyrimidine (cytosine, thymine, uracil).
• The base attaches to the sugar’s C-1′ atom through an N-β-glycosyl bond (N-9 for purines, N-1 for pyrimidines), and the phosphate attaches to the C-5′ atom.
Purine and Pyrimidine Bases
• DNA and RNA share adenine (A), guanine (G), and cytosine (C).
• DNA contains thymine (T) instead of uracil (U); RNA contains uracil instead of thymine.
• Minor bases—such as 5-methylcytidine, N6-methyladenosine, and pseudouridine—appear in specialized roles, often regulating gene expression or stabilizing RNA structure.
Pentose Sugars and Nucleic Acid Identity
• The pentose sugar defines whether a nucleic acid is DNA or RNA:
– DNA contains 2′-deoxy-D-ribose.
– RNA contains D-ribose.
• The sugar is always in its closed β-furanose ring form in both DNA and RNA.
• The nucleic acid’s identity depends on the sugar, not the bases: a molecule with deoxyribose is DNA even if it contains uracil.
Nucleotide Naming and Conventions
• Nucleoside + phosphate = nucleotide (e.g., adenosine → adenylic acid).
• “Deoxy-” is added for DNA components (e.g., deoxyadenosine → deoxyadenylate).
• The carbon and nitrogen atoms in sugars and bases are numbered separately; sugar atoms carry primes (1′, 2′, 3′, etc.).
Linkages and Polarity of Nucleic Acids
• Nucleotides are joined by phosphodiester bonds between the 3′-hydroxyl of one sugar and the 5′-phosphate of the next.
• The alternating sugar-phosphate backbone is highly polar and hydrophilic, while bases act as hydrophobic side chains.
• All linkages share the same orientation, giving nucleic acids a directional polarity: one end is 5′ (phosphate terminus), the other 3′ (hydroxyl terminus).
• Sequences are always written from 5′ → 3′ (e.g., 5′-ACGTA-3′).
• Short chains (<50 nucleotides) are called oligonucleotides; longer ones are polynucleotides.)
Stability and Hydrolysis
• The covalent backbone is stable but can undergo nonenzymatic hydrolysis.
• RNA is less stable than DNA under alkaline conditions because its 2′-OH group participates in intramolecular cleavage, forming cyclic 2′,3′-monophosphates before further hydrolysis.
• DNA lacks the 2′-OH group, making it resistant to base-catalyzed degradation.
Chemical Properties of Bases
• Purines and pyrimidines are aromatic, planar, weakly basic molecules that can exist in multiple tautomeric forms (e.g., uracil has lactam and lactim forms).
• At physiological pH, nucleic acid bases absorb strongly at 260 nm due to conjugated π-electron systems—used to quantify DNA and RNA spectroscopically.
Base Pairing and Interactions
• Bases stack through hydrophobic and van der Waals interactions, minimizing water contact and stabilizing nucleic acid structure.
• Complementary hydrogen bonding allows base pairing—A pairs with T (or U), and G pairs with C—according to Watson and Crick’s model.
• These specific pairings enable accurate DNA replication and RNA transcription.
Modified Nucleotides and Variations
• Cells also contain cyclic and alternative phosphate derivatives such as adenosine 2′,3′-cyclic monophosphate, AMP, and cyclic AMP (cAMP), which function as metabolic intermediates and signaling molecules.
In a Nutshell
Nucleic acids are polymers of nucleotides composed of a nitrogenous base, a pentose sugar, and phosphate groups. DNA contains deoxyribose and thymine, while RNA contains ribose and uracil. The sugar-phosphate backbone establishes 5′→3′ polarity, and base stacking and hydrogen bonding govern structural stability and information pairing. These molecular conventions define how genetic information is encoded, transmitted, and expressed through the complementary structures of DNA and RNA.