Nucleic acid
Friedrich Miescher in 1869
* Isolated what he called nuclein from the nuclei of pus cells.
* Nuclein was shown to have acidic properties, hence it becomes called nucleic acid.
Nucleotides and Nucleic acid
* Nucleotides have a variety of roles in cellular metabolism.
* They are the energy currency in metabolic reactions, the essential chemical links in the response of cells to hormones and other stimuli and the structural components of a variety of enzyme cofactors and metabolic intermediates.
* They are also constituents of the nucleic acid, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).
* The amino acid sequence of every protein in a cell, and the nucleotide sequence of every RNA, is specified by a nucleotide sequence in genomic DNA.
Nucleic acid
• Function :
• Store & transmit genetic information
• Examples :
• RNA (ribonucleic acid) (rRNA, mRNA, tRNA).
• DNA (deoxyribonucleic acid)
• ATP (adenosine triphosphate)
• Supplies energy for synthetic reactions and for other energy requiring processes in cells.
Structure :
• Monomers = nucleotides
• Polymers = polynucleotides (DNA, RNA).
Nucleotides
3 Parts
• Nitrogen base (C-N ring)
• Pentose sugar (5C)
• ribose in RNA
• deoxyribose in DNA
• Phosphate (PO4) group
Structure of Nucleotides
• Nucleotides contain three components : 1) a nitrogen containing base, 2) a pentose and 3) one or more phosphates.
• In the absense of the phosphate group(s), the molecule is called a nucleoside.
• The nitrogenous bases are derivatives of pyrimidine and purine.
• The numbering of the ring atoms of pyrimidines and purines is illustrated.
• The base of a nucleotide is joined covalently (at N-1 of pyrimidines and N-9 of purines) in an N-β-glycosyl bond to the 1' carbon of the pentose and the phosphate is esterified commonly to the 5' carbon.
• Water is removed in the formation of the N-β-glycosyl bond as occurs in O-glycosidic bond formation.
Major Bases of Nucleic Acids
• Both DNA and RNA contain two major purine bases, adenine (A), and guanine (G).
• Both nucleic acids also contain the pyrimidine, cytosine (C) and a second pyrimidine that is thymine (T), in DNA and uracil (U) in RNA.
• Only occasinally does thymine occur in RNA or uracil in DNA.
• In some cases the names of the bases reflect the sources from which they originally were isolated.
• Guanine, for example, was first isolated from guano (bird manure) and thymine was first isolated from thymus tissue.
• Five nucleobases - adenine (A), cytosine (C), guanine (G), thymine (T) and uracil (U) - are called primary or canonical.
Nitrogen bases
• Nucleobases. also known as nitrogenous bases or often simply bases, are nitrogen containing biological compounds that form nucleosides.
• Nucleosides are components of nucleotides, with all of these monomers containing the basic building blocks of nucleic acids.
• The ability of nucleobases to form base pairs and to stack one upon another leads directly to long-chain helical structures such as ribonucleic acid (RNA) and deoxyribonucleic acid (DNA).
• A and G classified as purines. The primary distinguishing structural feature of a purine is double carbon-nitrogen ring.
• C, T and U are classified as pyrimidines. These are structurally distinguished by a single carbon-nitrogen ring.
Complementary base pairing
• It is the most important structural feature of nucleic acids.
• If connects bases of one polynucleotide chain (nucleotide polymer) with complementary bases of other chain.
• Complementary bases are bonded together via :
- Double hydrogen bond between A and T (DNA), A and U (RNA) (A=T or A=U).
- Triple hydrogen bond between G and C in both DNA or RNA (G=C).
Significance of complementary base pairing
• The importance of such complementary base pairing is that each strand of DNA can act as template to direct the synthesis of other strand similar to its complementary one.
• Thus nucleic acids are uniquely capable of directing their own self replication.
• The information carried by DNA and RNA direct the synthesis of specific proteins which controls most cellular activities.
Minor Bases
Both DNA and RNA also contain some minor bases. In DNA, the most common of these are methylated forms of the major bases (panel a). Minor bases of many types occurs directly on one of the ring atoms of the pyrimidine or purine base, the convention is to simply indicate the ring position of substituent by its number, e.g. 5-methylcytidine. The convention changes when the substituent atom is exocyclic (not within the ring structure). In this case the type of atom is denoted with a superscript, e.g. N6-methyladenosine.
Nomenclature of Nucleosides & Nucleotides
The names of the nucleotides and nucleotides containing the five common bases are listed in table.
The pentoses of Nucleotides
• Nucleotide have two kinds of pentoses.
• The recurring deoxyribonucleotide units of DNA contain 2'-deoxy-D-ribose and the ribonucleotide unit of RNA contain D-ribose.
• The pentose sugar contains five carbon atoms.
• Each carbons atom of the sugar molecules are numbered as 1',2',3',4' & 5'.
• The two main functional groups that are attached to the sugar are often named in reference to the carbon to which they are bound. For example, the phosphate residue is attached to the 5' carbon of the sugar and the hydroxyl group is attached to the 3' carbon of the sugar.
• The pentose sugar in DNA is called deoxyribose and in RNA, the sugar is ribose.
• The difference between the sugars in the presence of the hydroxy group on the 2' carbon of the ribose and its absence on the 2' carbon of the deoxyribose.
The phosphate group
• There can be anywhere between one and three phosphate groups bound to the 5' carbon of the sugar.
• When one phosphate is bound, the nucleotide is referred to as a Nucleotide Monophosphate (NMP).
• If two phosphate are bound the nucleotide is referred to as Nucleotide Diphosphate (NDP).
• When three phosphate are bound to the nucleotide it is referred to as a Nucleotide Triphosphate (NTP).
• The phosphoanhydride bonds between that link the phosphate groups to each other have specific chemical properties that make them good for various biological functions.
• The hydrolysis of the bonds between the phosphate groups is thermodynamically exergonic in biological conditions; nature has evolved numerous mechanisms to couple this negative change in free energy to the drive many reactions in the cell.
DNA
Winners of the Race to learn DNA's structure - Watson and Crick
Discovery of DNA structure by x-ray Diffraction Technology.
James D. Watson and Francis H.C. Crick, the American graduate student and the British biochemist, who correctly explained the structure of DNA.
a) The scientists as they appeared in 1952, when the structure of DNA was formulated.
b) Photographs of more recent vintage.
* The scientific frame work for their breakthrough was provided by other scientists including.
* Linus Pauling
* Rosalind Frankin and Maurine Wilkins.
* Erwin Chargaff
* Rosalind Frankin
* She worked is some laboratory as Maurice Wilkins.
* She study x-ray diffraction to study wet fibers of DNA.
• She made marked advances in x-ray diffraction techniques with DNA.
• The diffraction pattern she obtained suggested several structural features of DNA.
• Helical
• More than one strand
• 10 base pairs per complete turn.
Deoxyribonucleotides of DNA
• The structures and names of the four major deoxyribonucleotides (deoxyribonucleoside 5'-monophosphate) of DNA.
• All nucleotides are shown in their free form at pH 7.0.
• The deoxyribonucleotide units of DNA are usually symbolized as A,G,T and C and sometimes as dA, dG , dT and dC .
• In their free forms, the deoxyribonucleotides are commonly abbreviated dAMP, dGMP, cTMP and dCMP.
• For each nucleotide in the figure, the more common name is followed by the complete name is parentheses.
• All abbreviations assume that the phosphate group is at the 5' position.
• The nucleoside portion of each molecule is shaded in light red.
DNA structure
* DNA is a double stranded molecules consists of 2 polynuclotide chains running in opposite directions.
* Both strands are complementary to each other.
* The bases are on the inside of the molecules and the 2 chains are joined together by double H-bond between A and T and triple H-bond between C and G.
* The base pairing is very specific which make the 2 strands complementary to each other.
* So each strand contains all the required information for synthesis (replication) of a new copy to its complementary.
* DNA stands