Jun 9, 2012

Nucleic Acid - an overview

Nucleic acid is essential for life. The term ‘nucleic acid’ comes from the fact that they are found mainly in nucleus. Nucleic acid was first isolated in 1870 by F. Miescher from the nuclei of pus cells. The two major types of nucleic acid found in the living things are deoxyribonucleic acid (DNA) and Ribonucleic acid (RNA). Nucleic acid is a linear un-branched polymer. The monomer of the nucleic acid is called nucleotide.

 

Structure of a Typical Nucleotide

Each nucleotide consists of pentose sugar, a phosphate and nitrogen containing ring structure called bases. The ring structures are called bases because of unshared pair of electrons on nitrogen atoms, which can thus acquire a proton. Phosphoric acid (H3PO4) which gives nucleic acid their acid characteristics forms the ester linkage with OH groups of a pentose sugar. In a typical structure the nitrogen base is attached to position 1 of pentose sugar. One phosphoric acid is attached with two pentose sugars with one ribose at position 3 and at position 5 of another ribose. The combination of a sugar with a base acid addition of phosphoric acid is condensation reactions.

Nucleoside: Base - Sugar

Nucleotide: Sugar - Phosphate – Sugar

Phosphate diester linkage: Phosphate forms linkage with two pentose sugars, the linkage is called phosphodiester linkage.

Bases may be grouped as: Purine and Pyrimidine.



Purine: Includes Adenine and Guanine which are double ring structures.

Pyrimidine: It includes Thymine, Cytosine and Uracil, which are single ring structures.

The nucleotides are named after the name of base attached to it e.g. Adenine nucleotide Adenine-deoxyribose- phosphate. Bases are represented by their initial letter i.e. A, G, T, C, and U.

Nucleotides are not only used as building blocks for nucleic acids, but they form several coenzymes, including adenosine triphosphate (ATP), nicotnamide dinucteotides (NAD).

Polynucleotide

Two nucleotides join to form a dinucleotide by condensation between the phosphate of one with the sugar of the other. The process is repeated up to several million times to make a polynucleotide. An unbranched sugar- phosphate backbone is thus formed.


Mononucleotide

Adenosine monophosphate (AMP) is a type of nucleotide consisting of a ribose sugar and the base adenine. When a phosphate group is added to AMP, it becomes Adenosine diphosphate (ADP). Further addition of another phosphate group to ADP results in the formation of Adenosine triphosphate (ATP), which is considered the most crucial high-energy compound found in all cells. The two covalent bonds that connect these three phosphates in ATP are often denoted by a squiggle (~) and are referred to as high-energy bonds. The process of adding an inorganic phosphate group to an organic molecule is known as phosphorylation e.g. ADP+P=ATP

ATP a rich energy compound

ATP can be converted to ADP and inorganic phosphate (Pi) by hydrolysis.

This reaction releases energy.

The third phosphate group splits from the ATP, and this phosphate remains in the cell in inorganic form. ADP and phosphate can be converted back to ATP, by condensation the two reactions can be put together:

ATP is known as the energy currency of cells. ATP can be used to make muscles contract, make nerve function, drive active transport and synthesis of proteins etc. ATP is made from the oxidation of organic molecules during respiration. Since the energy to add the phosphate to ADP comes from oxidation, the process is known as oxidative phosphorylation. In photosynthesis ATP is made by using light and the process is called photophosphorylation. Most of the ATP in the cell is made in mitochondria. The actual amount of ATP in the cell at any time is small.

 

Dinucleotide-NAD

Often enzymes use additional chemical components called cofactors as a tool to aid the catalysis. When the cofactor is an organic compound other than proteins it is called a coenzyme e.g. Nicotinamide-adenine dinucleotide (NAD) and many vitamins.

Structure: It consists of two nucleotides. One nucleotide consists of base-nicotinamide, sugar and phosphate. Other nucleotide consists of base-adenine-sugar and phosphate. The two bases are joined by their phosphate group forming a dinucleotide. It is derived from the vitamin nicotinic acid (niacin) and can exist in both reduced and oxidized form.

NAD-as coenzyme: In many enzyme-catalyzed oxidation-reduction reactions, the electrons are passed in pairs from the active site of enzyme to a coenzyme that serves as the electron acceptor. When NAD acquires an electron and hydrogen atom (actually two electrons and a proton) from the active site of an enzyme, it becomes reduced as NADH. The two energetic electrons and the proton are now carried by NADH molecule. The oxidation of food stuff takes place by taking electrons and donating them to NAD forming NADH. Only a small amount of NADH molecule is present in a cell, because each NAD molecule is used over again and again. FAD (Flavin adenine dinucleotide) is another coenzyme for oxidation reduction, which is sometimes used instead of NADH+. FAD accepts two electrons and two hydrogen ions (H+) to become FADH2.

Deoxyribonucleic Acid (DNA)

It is generally present in the chromosome. It is also found in mitochondria and chloroplast. It consists of:

1. Pentose Sugar: Deoxyribose 2. Purine: Adenine, Guanine

3. Pyrimidine: Thymine, Cytosine 4. Phosphate

Structure of DNA: Maurice Wilkins and Rosalind Franklin used the technique of x-ray diffraction to determine the structure of DNA. At the same time James D. Watson and Francis Crick built the scale model of DNA. All the data thus obtained strongly suggested that DNA is a double helix structure. There are two polynucleotide strands running in opposite directions and winding about each other in a form of double helix. The double helix looks like a ladder. The sugar phosphate part of the nucleic acid makes the upright part of the ladder. The nitrogen bases of the nucleotide make up the rungs of the ladder. Each rung consists of Purine and a Pyrimidine. Adenine pairs with thymine and guanine pairs with cytosine. The base pairs are held together by the hydrogen bond. There are two hydrogen bonds between A and T and three hydrogen bonds between C and G. The helix is 20A° (2nm) in diameter and makes a full spiral turn every 34 A° (3.4nm) i.e.  After every ten base pairs. The distance between two base pairs is 0.34 nm.

a. There are four different nucleotides in DNA; each contains phosphate, the pentose sugar deoxyribose, and a nitrogen-containing organic base. Two bases are purines:

Adenine (A) and guanine (G): two bases are pyrimidnes:thymine (T) and cytosine (C).

b. DNA has a ladder structure: the sugar-phosphate molecules make up the sides and the hydrogen-bonded bases make up the rungs.

c. Actually, DNA is a double helix in which the two strands twist about each other.

The amount of DNA is fixed for particular species. It depends upon the number of chromosomes. All the somatic (body) cells of an organism have the same amount of DNA, while the sperms or ova have almost half the amount of DNA.

 

Ribonucleic Acid (RNA) The carrier of Information

RNA is concentrated in the cytoplasm. It consists of sugar Ribose and bases Adenine, Uracil, Cytosine and Guanine. RNA is hereditary material in some viruses. RNA is a single polynucleotide chain. There are three types of RNA molecules:   (1) tRNA = transfer RNA. (2) rRNA = ribosomal RNA. (3) mRNA= messenger RNA

The three RNA are synthesized from different parts of DNA in a process called transcription. The synthesis takes place in the nucleus. Then the RNA is transported to cytoplasm.

1. Messenger RNA (mRNA): It takes the genetic message from the nucleus to the ribosomes in the cytoplasm to form particular proteins. Base sequence in mRNA is according to the base sequence of DNA. It becomes attached to ribosome, where amino acids are attached to form polypeptide chain as per base sequence of mRNA. A mRNA consists of a single strand of variable length. Its length depends upon the size of the gene as well as the protein for which it is taking the message. For example, for a protein molecule 1,000 amino acids, mRNA will have the length of 3,000 nucleotides. mRNA is about 3 to 4% of the total RNA in the cell.

2. Transfer RNA (tRNA): These are small molecules. Each chain consists of 75 to 90 nucleotides. Specific tRNA will pick specific amino acid. It will bring the amino acid to the ribosomes as per nucleotide sequence of rRNA. So the cell will have at least 20’ kinds of tRNA molecules. tRNA comprises about 10 to 20% of the cellular RNA.

3. Ribosomal RNA (rRNA): It consists of rRNA and protein. mRNA has the genetic information according to DNA. In ribosome the amino acids are arranged and linked as per sequence of nucleotides on the-mRNA. Thus specific protein molecules are synthesized. It is the major portion of RNA in the cell, and may be up to 80% of the total RNA. It is strongly associated with the ribosomal protein where 40 to 50% of it is present.



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