CHAPTER 21: Unit 1. NUCLEIC ACID: INTRODUCTION

Nucleic acids are the most important of all biomolecules. These are found in abundance in all living things, where they function to create and encode and then store information of every living cell of every life-form organism on Earth. In turn, they function to transmit and express that information inside and outside the cell nucleus—to the interior operations of the cell and ultimately to the next generation of each living organism. The encoded information is contained and conveyed via the nucleic acid sequence, which provides the ‘ladder-step’ ordering of nucleotides within the molecules of RNA and DNA.

Nucleic acids are the basic molecular structures present in DNA and RNA, which ultimately for the blueprint for our genetic information. Like protein and carbohydrates, nucleic acids are polymers. Proteins are polypeptides, carbohydrates are polysaccharides, and nucleic acids are polynucleotides.

Tow kinds of nucleic acids are found in cells: Ribonucleic acid (RNA) and Deoxyribonucleic acid (DNA). Each plays an important role in the transmission of hereditary information. DNA presents in chromosomes of the nuclei of eukaryotic cells. RNA is not found in the chromosomes, but rather, is located elsewhere in the nucleus and even outside the nucleus, in the cytoplasm. Both the DNA and the RNA are polymers.

Nucleic acids are molecules made up of nucleotides that direct cellular activities such as cell division and protein synthesis. Ribosomal RNA (rRNA) is a part of the ribosomes at the site of protein synthesis, whereas transfer RNA (tRNA) carries the amino acid to the site of protein synthesis.

Nucleic acids are polymers of acidic monomeric subunits known as nucleotides. The nucleotides form a duplex, or double-stranded, molecule referred to as deoxyribonucleic acid (DNA) that stores genetic information within the cell. The genetic information in DNA is transferred to ribonucleic acid (RNA), monomeric forms of nucleic acids that are primarily single-stranded molecules. The three major RNA species differ in their composition and function. These are designated ribosomal RNA (rRNA), transfer RNA (tRNA), and messenger RNA (mRNA).

DNA and RNA each consists of only four different nucleotides. All nucleotides have a common structure: a phosphate group linked by a phosphoester bond to a pentose (a five-carbon sugar molecule) that in turn is linked to an organic base (Figure 4-1a). In RNA, the pentose is ribose; in DNA, it is deoxyribose (Figure 2-1b). The only other difference in the nucleotides of DNA and RNA is that one of the four organic bases differs between the two polymers. The bases adenine, guanine, and cytosine are found in both DNA and RNA; thymine is found only in DNA, and uracil is found only in RNA. The bases are often abbreviated A, G, C, T, and U, respectively. For convenience the single letters are also used when long sequences of nucleotides are written out.

Figure-1 All Nucleotides have a common structure(a) Chemical structure of adenosine 5′-monophosphate (AMP), a nucleotide that is present in RNA. All nucleotides are composed of a phosphate moiety, containing up to three phosphate groups, linked to the 5′ hydroxyl of a pentose sugar, whose 1′ carbon is linked to an organic base. By convention, the carbon atoms of the pentoses are numbered with primes. In natural nucleotides, the 1′ carbon is joined by a β linkage to the base, which is in the plane above the furanose ring, as is the phosphate. (b) Haworth projections of ribose and deoxyribose, the pentoses in nucleic acids.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK21514/

The base components of nucleic acids are heterocyclic compounds with the rings containing nitrogen and carbon. Adenine and guanine are purines, which contain a pair of fused rings; cytosine, thymine, and uracil are pyrimidines, which contain a single ring (Figure-2). The acidic character of nucleotides is due to the presence of phosphate, which dissociates at the pH found inside cells, freeing hydrogen ions and leaving the phosphate negatively charged (Figure-2). Because these charges attract proteins, most nucleic acids in cells are associated with proteins. In nucleotides, the 1′ carbon atom of the sugar (ribose or deoxyribose) is attached to the nitrogen at position 9 of a purine (N9) or at position 1 of a pyrimidine (N1).

Figure-2 The chemical structures of the principal bases in nucleic acidsIn nucleic acids and nucleotides, nitrogen 9 of purines and nitrogen 1 of pyrimidines (red) are bonded to the 1′ carbon of ribose or deoxyribose

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CHEMISTRY OF NUCLEIC ACID

History: In 1869 Friedrich Miescher developed ways of isolating intact nuclei from cells and analyzing their chemical content. From the nuclei he extracted substances rich in phosphorus and nitrogen. They came to be known as “nucleic acids.” Miescher predicted that they would someday be considered as important as proteins. The substances turned out to be deoxyribonucleic acid (DNA) which was found by Avery, MacLeod and McCarty in 1944 to be the genetic material. They proved this clearly by using bacterial DNA to change (transform) the genetic material of other bacteria.Nucleic acids, which are relatively strong acids found in the nuclei of cells, were first isolated in 1869. The nucleic acids are polymers with molecular weights as high as 100,000,000 grams per mole. They can be broken down, or digested, to form monomers known as nucleotides. Each nucleotide contains three units: a sugar, an amine, and a phosphate, as shown in the figure-3 below.

Figure-3 Classes of Nucleic Acids

Nucleic acids are divided into classes on the basis of the sugar used to form the nucleotides. Ribonucleic acid (RNA) is built on a b-D-ribofuranose ring. Deoxyribonucleic acid (DNA) contains a modified ribofuranose in which the -OH group on the second carbon atom has been removed, as shown in the fiugre below.

Purines and Pyrimidines

The amines that form nucleic acids fall into two categories: purines and pyrimidines. There are three pyrimidines  cytosine, thymine, and uracil and two purines  adenine and guanine, as shown in the figure below.

DNA and RNA each contain four nucleotides. Both contain the same purines adenine and guanine and both also contain the pyrimidine cytosine. But the fourth nucleotide in DNA is thymine, whereas RNA uses uracil to complete its quartet of nucleotides.

Reference: https://www.britannica.com/science/nucleic-acid

Role of Nucleic Acids in Living Systems

For many years, the role of nucleic acids in living systems was unknown. In 1944 Oswald Avery presented evidence that nucleic acids were involved in the storage and transfer of the genetic information needed for the synthesis of proteins. This suggestion was actively opposed by many of his contemporaries, who believed that the structure of the nucleic acids was too regular  and therefore too dull to carry the information that codes for the thousands of different proteins a cell needs to survive.In retrospect, the first clue about how nucleic acids function was obtained by Erwin Chargaff, who found that DNA always contains the same amounts of certain pairs of bases. There is always just as much adenine as thymine, for example, and just as much guanine as cytosine.In 1954, James Watson and Francis Crick proposed a structure for DNA that explained how DNA could be used to store genetic information. Their structure consisted of two polynucleotide chains running in opposite directions that were linked by hydrogen bonds between a specific purine (A or G) on one strand and a specific pyrimidine (C or T) on the other, as shown in the figure below. These strands form a helix that is not quite as tightly coiled as the a-helix Pauling and Corey proposed for proteins.

This structure must be able to explain two processes. There must be some way to make perfect copies of the DNA that can be handed down to future generations (replication). There also must be some way to decode the information on the DNA chain (transcription) and translate this information into a sequence of amino acids in a protein (translation).Replication is easy to understand. According to Watson and Crick, an adenine on one strand of DNA is always paired with a guanine on the other, and a cytosine is always paired with a thymine. The two strands of DNA therefore complement each other perfectly; the sequence of nucleotides on one strand can always be predicted from the sequence on the other. Replication occurs when the two strands of the parent DNA molecule separate and both strands are copied simultaneously. Thus, one strand from the parent DNA is present in each of the daughter molecules produced when a cell divides.

Reference: https://www.dummies.com/education/science/biology/what-is-the-role-of-nucleic-acids-in-living-things/

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