Difference Between Nucleotide and Nucleoside — Structure, Examples & Comparison

The key difference is the presence of a phosphate group:

Nucleoside = Nitrogenous Base + Pentose Sugar Nucleotide = Nitrogenous Base + Pentose Sugar + Phosphate Group

Or simply: Nucleotide = Nucleoside + Phosphate Group

Components: • Nucleoside has 2 components: base + sugar • Nucleotide has 3 components: base + sugar + phosphate

Example: • Adenosine (nucleoside) = Adenine + Ribose • Adenosine monophosphate / AMP (nucleotide) = Adenine + Ribose + 1 Phosphate • ATP (nucleotide) = Adenine + Ribose + 3 Phosphates

Think of it this way: • Nucleoside is like a car without fuel (no phosphate = no energy) • Nucleotide is the car with fuel (phosphate bonds store energy)

A nucleoside consists of two components bonded together:

1. Nitrogenous Base (attached at the 1' carbon of the sugar) Purines (double ring): Adenine (A), Guanine (G) Pyrimidines (single ring): Cytosine (C), Thymine (T), Uracil (U)

2. Pentose Sugar • Ribose (in RNA nucleosides) — has an –OH group at the 2' carbon • Deoxyribose (in DNA nucleosides) — has only –H at the 2' carbon

Bond: The base and sugar are connected by a glycosidic bond (specifically, a β-N-glycosidic bond) between the N-9 of purines or N-1 of pyrimidines and the 1' carbon of the sugar.

Naming nucleosides: • Adenine + Ribose = Adenosine • Guanine + Ribose = Guanosine • Cytosine + Ribose = Cytidine • Thymine + Deoxyribose = Thymidine • Uracil + Ribose = Uridine

For DNA nucleosides, add 'deoxy-' prefix: • Adenine + Deoxyribose = Deoxyadenosine • Guanine + Deoxyribose = Deoxyguanosine

A nucleotide consists of three components:

1. Nitrogenous Base: Adenine, Guanine, Cytosine, Thymine (DNA), or Uracil (RNA)

2. Pentose Sugar: Ribose (RNA) or Deoxyribose (DNA)

3. Phosphate Group(s): One, two, or three phosphate groups attached at the 5' carbon of the sugar via a phosphoester bond

Types based on phosphate groups: • Nucleoside monophosphate (NMP): 1 phosphate (e.g., AMP, GMP, CMP) • Nucleoside diphosphate (NDP): 2 phosphates (e.g., ADP, GDP) • Nucleoside triphosphate (NTP): 3 phosphates (e.g., ATP, GTP, CTP, UTP)

Naming nucleotides: • Adenosine + 1 Phosphate = Adenosine monophosphate (AMP) / Adenylic acid • Guanosine + 1 Phosphate = Guanosine monophosphate (GMP) / Guanylic acid • Cytidine + 1 Phosphate = Cytidine monophosphate (CMP) / Cytidylic acid • Thymidine + 1 Phosphate = Thymidine monophosphate (TMP) / Thymidylic acid • Uridine + 1 Phosphate = Uridine monophosphate (UMP) / Uridylic acid

For DNA nucleotides, add 'deoxy-' prefix: dAMP, dGMP, dCMP, dTMP

Feature | Nucleoside | Nucleotide Components | Base + Sugar | Base + Sugar + Phosphate Phosphate group | Absent | Present (1, 2, or 3) Formula | Nucleoside = Base + Sugar | Nucleotide = Nucleoside + Phosphate Bond with sugar | Glycosidic bond (base–sugar) | Glycosidic bond + Phosphoester bond (sugar–phosphate) Charge | Neutral (no charge) | Negatively charged (due to phosphate) Role in DNA/RNA | Not a direct building block | Monomer (building block) of DNA and RNA Energy storage | Does not store energy | Stores energy in phosphate bonds (e.g., ATP) Examples | Adenosine, Guanosine, Cytidine, Thymidine, Uridine | AMP, ADP, ATP, GTP, dAMP, dGMP Found in | Metabolic intermediates, drugs | DNA, RNA, energy molecules (ATP, GTP), coenzymes (NAD⁺, FAD, CoA) Solubility | More hydrophobic | More hydrophilic (phosphate is polar) Molecular weight | Lower (no phosphate) | Higher (phosphate adds ~80 Da per group)

DNA Nucleosides and Nucleotides:

Base | Nucleoside | Nucleotide (monophosphate) Adenine (A) | Deoxyadenosine | Deoxyadenosine monophosphate (dAMP) Guanine (G) | Deoxyguanosine | Deoxyguanosine monophosphate (dGMP) Cytosine (C) | Deoxycytidine | Deoxycytidine monophosphate (dCMP) Thymine (T) | Thymidine | Thymidine monophosphate (dTMP)

RNA Nucleosides and Nucleotides:

Base | Nucleoside | Nucleotide (monophosphate) Adenine (A) | Adenosine | Adenosine monophosphate (AMP) Guanine (G) | Guanosine | Guanosine monophosphate (GMP) Cytosine (C) | Cytidine | Cytidine monophosphate (CMP) Uracil (U) | Uridine | Uridine monophosphate (UMP)

Naming pattern: • Purines (A, G): base name ending changes to '-osine' → Adenosine, Guanosine • Pyrimidines (C, T, U): base name ending changes to '-idine' → Cytidine, Thymidine, Uridine • Add 'monophosphate', 'diphosphate', or 'triphosphate' for nucleotides • Add 'deoxy-' prefix for DNA versions

Nucleotides serve many critical functions beyond building DNA and RNA:

1. Building blocks of DNA and RNA: • dATP, dGTP, dCTP, dTTP → used by DNA polymerase to build DNA • ATP, GTP, CTP, UTP → used by RNA polymerase to build RNA

2. Energy currency: • ATP (adenosine triphosphate) is the primary energy carrier in cells • ATP → ADP + Pi releases energy for cellular work • GTP provides energy for protein synthesis and cell signalling

3. Coenzymes and signalling: • NAD⁺ and NADH (contain adenine nucleotide) — electron carriers in cellular respiration • FAD and FADH₂ — electron carriers in Krebs cycle • Coenzyme A (CoA) — contains adenine nucleotide, essential for metabolism • cAMP (cyclic AMP) — second messenger in hormone signalling • cGMP — second messenger in vision and vasodilation

4. Allosteric regulators: • ATP and AMP regulate enzyme activity (e.g., phosphofructokinase in glycolysis)

5. Nucleoside drugs: • Antiviral drugs like Acyclovir (herpes), Zidovudine/AZT (HIV), and Remdesivir (COVID-19) are nucleoside analogues that block viral DNA/RNA replication

Nucleotides polymerise to form the long chains of DNA and RNA through phosphodiester bonds:

Phosphodiester Bond: • Forms between the 3'–OH of one nucleotide's sugar and the 5'–phosphate of the next nucleotide • A water molecule is released (condensation reaction) • This creates the sugar-phosphate backbone of DNA/RNA

DNA Structure: • Two polynucleotide chains running antiparallel (5'→3' and 3'→5') • Bases pair: A=T (2 hydrogen bonds), G≡C (3 hydrogen bonds) • Double helix structure (Watson and Crick, 1953) • Uses deoxyribonucleotides: dAMP, dGMP, dCMP, dTMP

RNA Structure: • Single polynucleotide chain (usually) • Uses ribonucleotides: AMP, GMP, CMP, UMP • Uracil replaces Thymine (U pairs with A) • Types: mRNA, tRNA, rRNA

Direction: • DNA and RNA strands have a 5' end (phosphate) and a 3' end (hydroxyl) • New nucleotides are always added at the 3' end • Polymerases read template 3'→5' and synthesise 5'→3'