5.1 Nucleotide structure and function

Nucleotides are the building blocks of DNA and RNA, playing crucial roles in genetic information storage and transmission. They consist of a nitrogenous base, a sugar, and phosphate groups, with variations in structure leading to different functions in cells.

Beyond their role in nucleic acids, nucleotides serve as energy carriers, enzyme cofactors, and signaling molecules. ATP powers cellular processes, while cyclic nucleotides like cAMP act as second messengers, regulating various biological responses and metabolic pathways.

Nucleotide Structure and Features

Components and Composition

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• Nucleotides consist of three main components form building blocks of nucleic acids
  • Nitrogenous base
  • Pentose sugar
  • One or more phosphate groups
• Nitrogenous bases classified into two categories
  • Purines (adenine, guanine)
  • Pyrimidines (cytosine, thymine, uracil)
• Pentose sugar varies between RNA and DNA
  • Ribose in RNA
  • Deoxyribose in DNA lacks hydroxyl group at 2' carbon
• Nucleotides connect through phosphodiester bonds
  • Bond forms between 3' carbon of one sugar and 5' carbon of next
  • Creates backbone of nucleic acids
• Structure allows specific base pairing via hydrogen bonding
  • Adenine pairs with thymine (DNA) or uracil (RNA)
  • Guanine pairs with cytosine

Phosphorylation States and Reactivity

• Nucleotides exist in various phosphorylation states
  • Monophosphates (NMP)
  • Diphosphates (NDP)
  • Triphosphates (NTP)
• Phosphorylation state affects reactivity and biological functions
  • Higher phosphorylation increases energy storage
  • Triphosphates (ATP) serve as energy currency in cells

Nucleotide Functions in Biology

Genetic Information Storage and Transmission

• Nucleotides serve as monomeric units for nucleic acid synthesis
  • DNA stores genetic information long-term
  • RNA transmits genetic information for protein synthesis
• Specific base pairing enables accurate replication and transcription
  • Complementary base pairing maintains fidelity of genetic information
  • Allows for semiconservative DNA replication

Cellular Energy and Metabolism

• ATP functions as primary energy currency in cells
  • Drives numerous biochemical reactions through hydrolysis
  • $ATP + H_2O \rightarrow ADP + P_i + energy$
• Nucleotides act as important enzyme cofactors
  • NAD+ and FAD participate in redox reactions during cellular respiration
  • $NAD^+ + 2e^- + H^+ \rightarrow NADH$
• Nucleotides participate in biomolecule synthesis
  • UDP-glucose involved in glycogen synthesis
  • CDP-diacylglycerol used in phospholipid biosynthesis

Signaling and Regulation

• Cyclic nucleotides serve as second messengers
  • cAMP and cGMP regulate cellular responses to external stimuli
  • Involved in various signal transduction pathways (hormone signaling)
• GTP plays specific roles in cellular processes
  • Participates in protein synthesis (elongation factor binding)
  • Involved in signal transduction through G-protein coupled receptors

Ribonucleotides vs Deoxyribonucleotides

Structural Differences

• Sugar composition varies between ribonucleotides and deoxyribonucleotides
  • Ribonucleotides contain ribose sugar
  • Deoxyribonucleotides contain deoxyribose sugar (lacks 2' hydroxyl group)
• 2' hydroxyl group in ribonucleotides impacts RNA properties
  • Makes RNA more susceptible to hydrolysis
  • Results in lower stability compared to DNA
• Base composition differs between RNA and DNA
  • RNA typically contains uracil as pyrimidine base
  • DNA contains thymine instead of uracil

Functional Implications

• Structural differences lead to distinct 3D conformations
  • RNA forms various secondary structures (hairpins, loops)
  • DNA primarily exists as double helix
• Precursor roles in nucleic acid synthesis
  • Ribonucleotides used in RNA synthesis
  • Deoxyribonucleotides used in DNA synthesis
• Interconversion between ribonucleotides and deoxyribonucleotides
  • Catalyzed by ribonucleotide reductase enzyme
  • Key step in de novo synthesis of DNA precursors
  • $Ribonucleotide + Thioredoxin_{red} \rightarrow Deoxyribonucleotide + Thioredoxin_{ox}$

Nucleotides in Energy and Signaling

Energy Transfer and Metabolism

• ATP serves as primary cellular energy carrier
  • Transfers energy through hydrolysis of high-energy phosphoanhydride bonds
  • $ATP + H_2O \rightarrow ADP + P_i + \sim 7.3 kcal/mol$
• ATP/ADP ratio acts as energy charge indicator
  • Regulates metabolic pathways through allosteric modulation
  • High ATP/ADP ratio inhibits catabolic pathways
  • Low ATP/ADP ratio activates catabolic pathways
• Nucleotides participate in metabolic regulation
  • Act as allosteric effectors influencing enzyme activity
  • Respond to cellular energy status (AMP activates glycolysis)

Signaling Pathways and Second Messengers

• GTP crucial in signal transduction
  • Acts as molecular switch in G-protein coupled receptor signaling
  • GTP binding activates G-proteins, while hydrolysis deactivates them
• Cyclic nucleotides function as second messengers
  • cAMP and cGMP amplify and propagate extracellular signals
  • Involved in various cellular processes (glycogen metabolism, smooth muscle relaxation)
• Regulation of cyclic nucleotide signaling
  • Synthesis by adenylyl cyclase and guanylyl cyclase
  • Degradation by phosphodiesterases
  • Controls duration and intensity of signaling events
• Nucleotide interconversion fine-tunes cellular processes
  • Kinases and phosphatases convert between ATP, ADP, and AMP
  • Provides mechanism for regulating energy metabolism and signaling pathways