Nucleotides and Nucleic Acids

Nucleotides and Nucleic Acids

• Nucleic acids were named because they were initially found in cell nuclei.
• There are two basic structural forms of nucleic acids: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).
• Nucleotides are the building blocks of nucleic acids, forming polymers in DNA and RNA.

Nucleotide Structure

• A nucleotide combines a nitrogenous base, a pentose sugar (5-carbon sugar), and a phosphoric acid (phosphate group).
• Nucleotides, which contain a nitrogenous base, sugar, and phosphate group, connect to form a nucleic acid chain, also known as a polynucleotide.
• A nucleoside is a combination of a sugar and a base.
• Nucleotides contain five different bases and two different sugars.
• The nitrogenous bases in nucleic acids have two structural types:
• Purines: adenine (A) and guanine (G) consist of two fused rings with nitrogen atoms.
• Pyrimidines: cytosine (C), thymine (T), and uracil (U) consist of a single ring with nitrogen atoms.
• Adenine (A), guanine (G), and cytosine (C) are present in both DNA and RNA.
• Thymine (T) is exclusively found in DNA, while uracil (U) is only found in RNA.
• The 5-carbon sugars in nucleic acids are D-ribose and D-deoxyribose.
• RNA nucleotides have ribose sugars.
• DNA nucleotides have deoxyribose sugars.
• Phosphoric acid in nucleotides is also called phosphate when ionized.
• Nucleotides link via their phosphoric acid portions.
• Three components of a mononucleotide: sugar, phosphate, and nitrogenous base, are joined by two condensation reactions.
• One between the sugar and phosphate, and the other between the sugar and the nitrogenous base.
• Nucleic acids first combine a nitrogen base and a 5-carbon sugar to form a nucleoside, then the nucleoside combines with phosphoric acid to form a nucleotide and nucleotide then becomes nucleic acid.
• When a nitrogen base and a 5-carbon sugar combine to form a nucleoside, the hydrogen from the nitrogen base approaches a sugar molecule containing an -OH (hydroxyl) group, forming water which is expelled and leaving a bond between the remaining fragments.
• Nucleoside naming:
• With ribose sugar, the base name (e.g., adenine) becomes adenosine.
• With deoxyribose sugar, add "deoxy-" prefix (e.g., adenine becomes deoxyadenosine).
• Phosphoric acid + nucleoside = nucleotide:
• A phosphate ester of a nucleoside forms via a condensation reaction between phosphoric acid and the alcohol group (OH-) on carbon 5.
• Example nucleotide: adenosine monophosphate (AMP).
• Nucleotides are the monomers of nucleic acids.
• AMP is a building block of RNA and is also involved in energy transfer.
• If the sugar is ribose, the result is one of four ribonucleotides and if the sugar is deoxyribose, the result is one of four deoxyribonucleotides.
• The monomers join by condensation reaction to become nucleic acids.
• In this condensation reaction, the phosphate of one nucleotide reacts with the alcohol group on carbon atom number 3' of another nucleotide.
• Nucleic acids form by joining nucleotides through condensation, involving the phosphate of one nucleotide reacting with the alcohol group on carbon atom number 3' of another nucleotide.
• The starting polymer end is 5', with the terminal end being 3'.

Nucleic Acids (DNA and RNA)

• Nucleic acids DNA and RNA share similarities and differences in structure and function.
• Both DNA and RNA are large molecules located in the cell nucleus.
• Main purpose: To store and direct information for cell reproduction/growth
• DNA stores genetic information in its structure
• DNA is the template strand in replication and transcription
• RNA transfers genetic information from DNA
• RNA delivers information to ribosomes for protein synthesis.
• Together, DNA and RNA enable life and known as the central dogma of genetics.
• DNA and RNA Structure:
• Both DNA and RNA are nucleotide polymers.
• DNA is larger (3 billion nucleotides in humans).
• Written as: 5'-C-G-T-A-3'
• DNA: 1-100 million nucleotides, while viral DNA is smaller.
• The three RNA types and sizes are rRNA (75-80%): 120-3,700 nucleotides, tRNA (10-15%): 70-90 nucleotides, and mRNA (remainder): ~1,200 nucleotides.
• Ribosomal RNA (rRNA) is found in ribosomes and synthesizes protein.
• Transfer RNA (tRNA) transfers amino acids to ribosomes.
• Messenger RNA (mRNA) carries DNA’s instructions and guides protein assembly.
• Extra Functions: RNA components in ATP, cAMP, FAD, NAD+, found in all plants, animals, and viruses have either DNA or RNA.
• DNA serves as the genetic material in most organisms.
• RNA plays genetic material role for some viruses (e.g. influenza virus).
  • mRNA carries genetic information to the site of protein synthesis, tRNA forms the link between messenger RNA and amino acids in protein synthesis, and rRNA is an essential component of ribosomes.

Nucleic Acids Structure (DNA)

• DNA is made of 2 polynucleotide strands held together by hydrogen bonds lined up with the bases pointing towards each other.
• The DNA strands run in opposite directions, described as anti-parallel with one strand running 5' to 3' while the other runs 3' to 5'.
• Base Pairing Rules:
• A pairs with T (2 hydrogen bonds) and G pairs with C (3 hydrogen bonds).
• In RNA, A pairs with U.
• Antiparallel Strands:
• The 5' end connects to a 3' end.
• Hydrophilic groups are outside, while hydrophobic bases are inside.
• Each purine is bonded to one pyrimidine.
• Strands mirror each other, meaning they are said to be complementary.
• Knowledge of one strand's sequence allows predicting the other strand's sequence.
• DNA strands twist into a double helix.
• B-Form DNA, is the most common DNA structure.
  • Shape: a double helix that is a right-handed spiral also exists as a common form in living cells.
  • Measurements: width = 2 nanometers, distance between base pairs = 0.34 nm where one full turn contains 10 base pairs and measures 3.4 nm long.
• A stable configuration is maintained by hydrogen bonds and base stacking force (hydrophobic interaction).
• In living cells, DNA must be efficiently packaged into within the cell while remaining functional with organization differing between prokaryotes and eukaryotes.
• Prokaryotic DNA Organization: DNA exists as a compact twisted structure called a supercoil essential for DNA packaging within the small cell space where The DNA is free in the cytoplasm without a nuclear membrane.
• Eukaryotic DNA Organization: DNA is highly organized and packaged within the nucleus with The structure alternating between Chromatin (a looser, more accessible form during most of the cell cycle) and Chromosomes, which are a highly condensed form (appears during metaphase).
• The fundamental packaging unit is the nucleosome, which consists of DNA around histone proteins.
• Importance of packing DNA into chromosomes:
• Chromosomes provide a compact form to fit inside cells.
• Chromosomes protect DNA from damage.
• DNA in a chromosome can be transmitted efficiently so daughter cells can undergo cell division.
• Chromosomes help achieve overall organization to each molecule of DNA which help with gene expression and recombination.

Genetic Concepts

• Gene: the minimum functional unit in DNA.
• Genome: the total genes in a living cell or living beings.
• A gene is a sequence of nucleotides along a DNA molecule that codes for polypeptide (protein) product.
• A triplet of nucleotides codes for one amino acid.
• A sequence of 3 bases (a triplet) is called a codon.
• Genetic code: the rule that determines which triplet nucleotides code for which amino acid.
• DNA nucleotides have identical structures regarding the sugar and phosphate groups but differ in nitrogenous bases.
• Sequence of bases in DNA determines the sequence of amino acids in a polypeptide chain (protein).
• Only 4 DNA bases: G, C, A, T, code for 20 amino acids found in polypeptides, and every three bases code for one amino acid where The maximum would be 64 different amino acids.
• This is why nature uses a triplet code (3 bases per amino acid).
• The extra combinations (64 versus 20 needed) allow for multiple codons coding for the same amino acid as well as special "stop" and "start" signals in the genetic code.
• Many amino acids are coded by more than one triplet codon, so the genetic code is considered degenerate.
• Some triplets' codons are called stop codons, which halt protein synthesis when they are reached.
• Character of the code: It is specific, universal and degenerative.
• Human genome (total genetic material in the cell) is divided into 46 DNA molecules or chromosomes and would measure approximately two meters in length if stretched.

Protein Synthesis

• DNA never leaves the nucleus (to large to fit) but a means of carrying its stored information is required in the cell cytoplasm.
• Messenger RNA (mRNA) acts as messenger between DNA and proteins, is single-stranded, created using DNA as a template, exists temporarily and can exit nucleus.

Nucleic acids structure (RNA)

• RNA does not contain Thymine (T), instead containing Uracil (U)
• DNA Base: Guanine (G) to RNA Base: Cytosine (C)
• DNA Base: Cytosine (C) to RNA Base: Guanine (G)
• DNA Base: Adenine (A) to RNA Base: Uracil (U)
• DNA Base: Thymine (T) to RNA Base: Adenine (A)
• Each tRNA molecule is specific for a particular amino acid.
• There are 20 different tRNAs, one for each amino acid.
• At one end of the tRNA molecule The appropriate amino acid binds, with the other end containing a three base sequence that is complementary to the triplet codon on mRNA. This region being called the anti-codon.
• tRNA binds to amino acids in the cytoplasm and transfers it to the ribosome.
• tRNA has a complex secondary structure due to many intra-strand hydrogen bonds.
• There are 45 different tRNA molecules so smaller numbers of tRNA is needed as the third base doesn't follow the pair rule:
• Wobble bases means that the complementary anti-codon can show some flexibility in the third base.
• If a codon ends in G, its anticodon can use either C or U where If a codon ends in U, its anticodon can use either A or G
• Two bases remain strict in their pairing where A at the end of a codon only pairs with U and C at the end of a codon only pairs with G.
• Wobble base pairing also affects how single strands of rTNA can recognize both codons/
• The third form of RNA is rRNA, which associates with some protein molecules to form ribosomes (sites of protein synthesis).

Protein Synthesis

• Two processes involve conversion DNA to RNA (transcription) and use if to create protiens (translation).
• DNA is converted to RNA
• It happens in the nucleus and uses RNA polymerase to makes mRNA copies of the gene turning it into complementary RNA.
• Movement of ribosome along mRNA
• Occurs during protein synthesis where mRNA moves exactly 3 nucleotides (1 codon) forward and is powered by ATP energy.

A. Transcription

• Transcription occurs in the nucleus.
• Synthesis of a molecule of RNA complementary to the gene sequence on DNA.
• Involves: Enzyme RNA polymerase.
• Steps include:
• RNA polymerase: Attaches to the double stranded DNA at the start codon.
• RNA polymerase: Start codon is always the codon for methionine
• RNA polymerase: Breaks the hydrogen bonds, Holding the two strands together/ causing the DNA to unwind into template and coding strand losing its helical shape.
• The new enzyme RNA polymerase catalyzes the synthesis of a molecule of RNA using one of the DNA strands also known as the Template strand.
• Template strand: The part of DNA that is transcribed into RNA/ and has Complementary sequences as a product.
• Coding strand: has identical sequence as formed RNA (with single exception).
• Both coding (exons) and non-coding (introns) regions of DNA/ are transcribed forming the immature mRNA.
• After RNA synthesis is over, introns will be excised and removed, joining remaining exons, to form mature mRNA in process of splicing.

B. Translation

• A text in "nucleic acid language" (DNA) translates into "protein language".
• Origin of the term "translation"
• The dictionary used for the translation is the genetic code.

Steps consist of:

• The mRNA travels through the nuclear pore binding to the ribosome, after reaching two codons are exposed as mRNA attaches to the ribosome.
• The tRNAs, specific for these codons, forms hydrogen bonds with mRNA the and tRNA-attached amino acid is joined with another amino acid to start protein synthesis.
• Once the bond is formed, ribosome moves along mRNA.
  • Ribosome moves one codon length (triplet) which exposes codon for another tRNA as Amino acids are bonded together and detach.
  • The new tRNA leaves the ribosome ready to pick-up-another amino acid, finally the translation stops as the translation encounters stop codon (no TRNA) or the ribosome "falls off".