NUCLEIC ACIDS Dr. Gamal Gabr, College of Pharmacy

 Deoxyribonucleic acid (DNA), which stays in the cell nucleus, and Ribonucleic acid (RNA), which functions in the cell cytoplasm.  Store and pass on essential genetic information that controls reproduction and protein synthesis.  DNA molecules are made up of the nitrogen- containing bases adenine, guanine, cytosine, and thymine; phosphoric acid (H 3 PO 4 ); and the simple sugar commonly called deoxyribose.  RNA molecules are composed of the nitrogen- containing bases adenine, guanine, cytosine, and uracil; phosphoric acid (H 3 PO 4 ); and the simple sugar ribose.

Dr. Gamal Gabr, College of Pharmacy Nucleotide structure  Nucleotides are composed of a nitrogenous base, a pentose monosaccharide, and one, two, or three phosphate groups.  The nitrogen-containing bases belong to two families of compounds: the purines and the pyrimidines.  Both DNA and RNA contain the same purine bases: adenine (A) and guanine (G).  Both DNA and RNA contain the pyrimidine cytosine (C), but they differ in their second pyrimidine base: DNA contains thymine (T), whereas RNA contains uracil (U).

Dr. Gamal Gabr, College of Pharmacy Nucleosides  The addition of a pentose sugar to a base produces a nucleoside. If the sugar is ribose, a ribonucleoside is produced; if the sugar is 2-deoxyribose, a deoxyribonucleoside is produced.  The ribonucleosides of A, G, C, and U are named adenosine, guanosine, cytidine, and uridine. Nucleotides  The addition of one or more phosphate groups to a nucleoside produces a nucleotide.

Dr. Gamal Gabr, College of Pharmacy

Digestion of nucleic acids  The nucleic acids in the diet are hydrolyzed to a mixture of nucleotides by ribonuclease and deoxyribonuclease presents in pancreatic and intestinal secretions.  Then the nucleotidases liberate the phosphate from nucleotides.  The resulting nucleosides are hydrolysed by nucleosidases forming free bases and pentose sugars.  Even when humans consume a diet rich in nucleoproteins, dietary purines and pyrimidines are not incorporated directly into tissue nucleic acids. Humans synthesize the nucleic acids, ATP, NAD+, coenzyme A, from amphibolic intermediates

Dr. Gamal Gabr, College of Pharmacy

Constituents of DNA and RNA

Dr. Gamal Gabr, College of Pharmacy  Nucleoside + phosphate yields phosphate ester nucleotide.

Dr. Gamal Gabr, College of Pharmacy  Polymerized nucleotide yields nucleic acid  In the nucleic acid the phosphate negative charges are neutralized by metal cations (such as Mg 2+ ) or positively charged proteins (histones).

Dr. Gamal Gabr, College of Pharmacy  It was figured out in 1953 by James D. Watson, an American scientist, and Francis Crick, a British scientist.  This model visualizes DNA as a so called double á-helix structure of oppositely wound polymeric strands held together by hydrogen bonds between opposing pyrimidine and purine groups.  In the secondary structure of DNA, only cytosine can be opposite guanine and only thymine can be opposite adenine and vice versa.  The two strands of DNA are complementary. This means that a particular portion of one strand fits like a key in a lock with the corresponding portion of another strand.

Nucleic Acids in Protein Synthesis Dr. Gamal Gabr, College of Pharmacy  When a new cell is formed, the DNA in its nucleus must be accurately reproduced from the parent cell.  Life processes are absolutely dependent upon accurate protein synthesis, as regulated by cell DNA  The DNA in a single cell must be capable of directing the synthesis of up to 3000 or even more different proteins.  The directions for the synthesis of a single protein are contained in a segment of DNA called a gene.  The process of transmitting information from DNA to a newly synthesized protein involves the following steps:

Nucleic Acids in Protein Synthesis Dr. Gamal Gabr, College of Pharmacy 1)The DNA undergoes replication: This process involves separation of a segment of the double helix into separate single strands. This process continues until a complete copy of the DNA molecule has been produced. 2)The newly replicated DNA produces messenger RNA (mRNA), a complement of the single strand of DNA, by a process called transcription. 3)A new protein is synthesized using mRNA as a template to determine the order of amino acids in a process called translation.

Dr. Gamal Gabr, College of Pharmacy

RECOMBINANT DNA AND GENETIC ENGINEERING  Segments of DNA contain information for the specific syntheses of particular proteins.  it has become possible to transfer this information between organisms by means of recombinant DNA technology, which has resulted in a new industry based on genetic engineering.  Most often the recipient organisms are bacteria, which can be reproduced (cloned) over many orders of magnitude from a cell that has acquired the desired qualities.  Therefore, to synthesize a particular substance, such as human insulin or growth hormone, the required genetic information can be transferred from a human source to bacterial cells, which then produce the substance as part of their metabolic processes.

RECOMBINANT DNA AND GENETIC ENGINEERING  The first step in recombinant DNA gene manipulation is to lyze (open up) a donor cell to remove needed DNA material by using enzyme action to cut the sought-after genes from the donor DNA chain.  These are next spliced into small DNA molecules. These molecules, called cloning vehicles, are capable of penetrating the host cell and becoming incorporated into its genetic material.  The modified host cell is then reproduced many times and carries out the desired biosynthesis.

RECOMBINANT DNA AND GENETIC ENGINEERING  Three types of RNA involved in comprising the structural and functional core for protein synthesis, serving as a template for translation, and transporting amino acid, respectively, are: mRNA, tRNA, rRNAmRNA, tRNA, rRNA  With 3'-AUG-5‘ mRNA codon would the tRNA in the diagram be able to form a codon-anticodon base pairing interaction3'-AUG-5‘  A gene is a segment of DNA that codes for a protein  mRNA takes the genetic code to the cytoplasm  The three nucleotide sequence on RNA is called a codon  In the ladder anology of the DNA molecule, the "rungs" of the ladder are paired nitrogenous bases  The enzymes that break hydrogen bonds and unwind DNA are helicases

RECOMBINANT DNA AND GENETIC ENGINEERING  Transcription results in messenger RNA  In RNA, one codon translate to one amino acid