Chemistry of Nucleic acids Nucleic acids What are

Chemistry of Nucleic acids

Nucleic acids • • What are the molecules of heredity? What are nucleic acids made of? What is the structure of DNA and RNA? What are the different classes of RNA?

The molecules of heredity • Each cell of our bodies contains thousands of different proteins. • How do cells know which proteins to synthesize out of the extremely large number of possible amino acid sequences? • From the end of the 19 th century, biologists suspected that the transmission of hereditary information took place in the nucleus, more specifically in structures called chromosomes. • The hereditary information was thought to reside in genes within the chromosomes. • Chemical analysis of nuclei showed chromosomes are made up largely of proteins called histones and nucleic acids.

The molecules of heredity – By the 1940 s, it became clear that deoxyribonucleic acids (DNA) carry the hereditary information. – Other work in the 1940 s demonstrated that each gene controls the manufacture of one protein. – Thus the expression of a gene in terms of an enzyme protein led to the study of protein synthesis and its control.

Nucleic acids • There are two kinds of nucleic acids in cells: – Ribo. Nucleic Acids (RNA) – Deoxyribo. Nucleic Acids (DNA) • Both RNA and DNA are polymers built from monomers called nucleotides. • A nucleotide is composed of: – a base, derived from purine or pyrimidine (nucleobases) – a monosaccharide, either D-ribose or 2 -deoxy-Dribose – and a phosphate.

Pyrimidine/Purine bases

Nucleosides • Nucleoside: a compound that consists of Dribose or 2 -deoxy-D-ribose covalently bonded to a purine or pyrimidine base by a -Nglycosidic bond.

Nucleotides • Nucleotide: a nucleoside in which a molecule of phosphoric acid is esterified with an -OH of the monosaccharide, most commonly either the 3’ or the 5’-OH.

In summary • A nucleoside + Base + Sugar • A nucleotide + Base + Sugar + Phosphate • A nucleic acid = A chain of nucleotides

Practice 1 • Adenosine 5’-triphosphate (ATP) is an important store energy gained from food. Draw the structure of AMP, ADP, ATP

Solution 1 • The base adenine is linked to a ribose unit by a β-N glycosidic linkage. The mono, di, and triphosphate is linked to C-5’ of the ribose by an ester bond

Structure of DNA and RNA • Schematic diagram of a nucleic acid molecule. The four bases of each nucleic acid are arranged in various specific sequences. Base sequence is read from the 5’ end to the 3’ end

Primary Structure of Nucleic Acid 13

DNA secondary structure • Secondary structure: the ordered arrangement of nucleic acid strands. – the double helix model of DNA 2° structure was proposed by James Watson and Francis Crick in 1953. • Double helix: a type of 2° structure of DNA in which two antiparallel polynucleotide strands are coiled (in a right-handed manner about the same axis) around each other.

The DNA double helix • Three-dimensional structure of a DNA double helix.

Base Pairing • Base pairing is complimentary • A major factor stabilizing the double helix is base pairing by hydrogen bonding between T-A and between C-G • T-A base pair comprised of 2 hydrogen bonds • G-C base pair comprised of 3 hydrogen bonds

Complementary base pairs • Only A could fit with T and G could fit with C • Two purines (AA, GG, AG) overlaps • Two pyrimidines (TT, CC, CT) too far apart • Combination of (AC, TG) are not found

Practice 2 • Write the complementary base sequence for the matching strand in the following DNA section: A-G-T-C-C-A-A-T-G-C

Solution 2 • Write the complementary base sequence for the matching strand in the following DNA section: A-G-T-C-C-A-A-T-G-C T-C-A-G-G-T-T-A-C-G

Higher structure of DNA – DNA is coiled around proteins called histones. – Histones are rich in the basic amino acids Lys and Arg, whose side chains have a positive charge. – The negatively-charged DNA molecules and positivelycharged histones attract each other and form units called nucleosomes. – Nucleosome: a core of eight histone molecules around which the DNA helix is wrapped. – Nucleosomes are further condensed into chromatin. – Chromatin fibers are organized into loops, and the loops into the bands that provide the superstructure of chromosomes.

Chromosomes

DNA and RNA • The three differences in structure between DNA and RNA are: – DNA bases are A, G, C, and T; the RNA bases are A, G, C, and U. – The sugar in DNA is 2 -deoxy-D-ribose; in RNA it is D-ribose. – DNA is always double stranded; there are several kinds of RNA, all of which are single-stranded.

Information transfer in cells

m. RNA • Messenger RNA, m. RNA: a ribonucleic acid that m. RNA carries coded genetic information from DNA to ribosomes for the synthesis of proteins – present in cells in relatively small amounts and very short-lived – single stranded – biosynthesis is directed by information encoded on DNA – a complementary strand of m. RNA is synthesized along one strand of an unwound DNA, starting from the 3’ end

Structure of t. RNA • Transfer RNA, t. RNA: – the smallest kind of the three RNAs – a single-stranded polynucleotide chain between 73 -94 nucleotide residues – carries an amino acid at its 3’ end – intramolecular hydrogen bonding occurs in t. RNA

r. RNA • Ribosomal RNA, r. RNA: a ribonucleic acid found in ribosomes, the site of protein synthesis – only a few types of r. RNA exist in cells – ribosomes consist of 60 to 65% r. RNA and 35 to 40% protein – in both prokaryotes and eukaryotes, ribosomes consist of two subunits, one larger than the other