Nucleic Acids: DNA and RNA Principles of Biochemistry (BCH 3000) Nucleic Acids: DNA and RNA Dr. Syahida Ahmad Department of Biochemistry Faculty of Biotechnology & Biomolecular Sciences UPM

Introduction Nucleic acids play main roles in the storage, transfer and expression of genetic information 2 types Deoxyribonucleic acid (DNA) Ribonucleic acid (RNA) DNA Primarily found in chromosome in the cell’s nucleus, some in mitochondria and chloroplast Repository of genetic information RNA 3 types: ribosomal, messenger and transfer Flow of biological information DNA  RNA  Proteins  Cell structure and function

Components of Nucleotides Nucleic acids are linear polymers built from four different monomers called nucleotides Nucleotides has three chemical parts Heterocyclic compound containing C, H, N and some O (Nitrogenous bases) 5-C carbohydrate (aldopentose) One, two or three phosphate groups

Nitrogenous bases of DNA and RNA Purine and pyrimidine Purine DNA: Adenine (A) and Guanine (G) RNA: Adenine (A) and Guanine (G) Pyrimidine DNA: Thymine (T) and Cytosine (C) RNA: Cytosine (C) and Uracil (U)

Aldopentoses of Nucleic Acids Two types of aldopentoses are found in the nucleic acids D-Ribose in RNA 2-D-deoxyribose in DNA The difference are 2'-OH (RNA) and 2'-H (DNA) affects secondary structure and stability Sugars make nucleosides more water-soluble

Nucleosides The linking of a nitrogenous base to an aldopentose through N-glycosidic linkages results in a nucleoside Named bases by adding -idine to the root name of a pyrimidine or -osine to the root name of a purine Pyrimidine - Cytidine and Uridine Purine – Adenosine and Guanosine Synthetic nucleosides used for treatment of certain diseases E.g. 3’-azidodeoxythymidine (AZT) and 2’,3’-dideoxyinosine (DDI) for treating AIDS patients

Drugs for treating AIDS

Nucleotides Forms when a phosphoryl group (-PO2-3) is linked to a carbohydrate -OH group on the nucleoside Common ester linkage is the –OH group on C-5’ of the pentoses Adenosine 5’-monophosphate (5’-AMP) – one phosphate Adenosine 5’-diphosphate (5’-ADP) – two phosphate Adenosine 5’-triphosphate (5’-ATP) – three phosphate Central to energy metabolism Other nucleoside triphosphates Guanosine triphosphate (GTP) – drives protein synthesis Uridine triphosphate (UTP) – drives carbohydrates metabolism Cytosine triphosphate (CTP) – drives lipid synthesis

Nucleic Acids DNA and RNA Forms when nucleotides are linked together through their phosphate groups 5’-phosphate group of one nucleotide is linked to the 3’-OH group of the next nucleotide 3’,5’-phosphodiester bond Sequence is always read 5' to 3' Backbone of DNA (and RNA) consists deoxyriboses (or riboses) and phosphate groups

DNA Consists of two polynucleotides strands folded into a double helix (double stranded) Stabilized by H bonds - Base pairs arise from H bonds Nucleotides contain a phosphate, a 2-Deoxyribose sugar, and one nitrogen base (A,T,C, or G) The secondary structure (3D) was elucidated by Watson and Crick in 1953 Complementary base pairing Guanine with Cytosine (G-C) Adenine with Thymine (A-T) Contain sugar 2-deoxyribose Make up chromosomes in the nucleus DNA, lacking 2'-OH is more stable than RNA This makes sense - the genetic material must be more stable RNA is designed to be used and then broken down

RNA Single stranded (a template copy) Complementary base pairing Guanine with Cytosine (G-C) Adenine with Uracil (A-U) Contain sugar Ribose Three types of RNA Ribosomal RNA (rRNA) - the basis of structure and function of ribosomes Messenger RNA (mRNA) - carries the message Transfer RNA (tRNA) - carries the amino acids

DNA & RNA Differences? Nucleotides strands DNA: double stranded (double helix) RNA: single stranded Complementary base pairing DNA: A-T, G-C RNA: A-U, G-C Sugar DNA: 2-D-deoxyribose RNA: D-Ribose Classes of Nucleic Acids DNA - one type RNA – rRNA, mRNA and tRNA

Amino Acids 20 amino acids are exist in nature Linked together in a process called protein synthesis in the cytoplasm to make polypeptides (subunits of proteins) DNA contains the instructions for making proteins but is too large to leave the nucleus mRNA codon table tells what 3 bases on mRNA code for each amino acid (64 combinations of 3 bases) Methionine (AUG) on mRNA is called the start codon because it triggers the linking of amino acids UAA, UGA,  & UAG on mRNA signal ribosomes to stop linking amino acids together

Genetic Code (RNA) Amino Acid 3 Letter Abbreviation Codons Alanine Ala  GCA GCC GCG GCU  Arginine  Arg  AGA AGG CGA CGC CGG CGU  Aspartic Acid  Asp  GAC GAU  Asparagine  Asn  AAC AAU  Cysteine  Cys  UGC UGU  Glutamic Acid  Glu  GAA GAG  Glutamine  Gln  CAA CAG  Glycine  Gly  GGA GGC GGG GGU  Histidine  His  CAC CAU  Isoleucine  Ile  AUA AUC AUU  Leucine  Leu  UUA UUG CUA CUC CUG CUU  Lysine  Lys  AAA AAG  Methionine  Met  AUG  Phenylalanine  Phe  UUC UUU  Proline  Pro  CCA CCC CCG CCU  Serine  Ser  AGC AGU UCA UCC UCG UCU  Threonine  Thr  ACA ACC ACG ACU  Tryptophan  Trp  UGG  Tyrosine  Tyr  UAC UAU  Valine  Val  GUA GUC GUG GUU  Start    Stop  UAA UAG UGA