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Principle of Biochemistry5-Nucleotides and Nucleic Acids

Course code: HFB324Credit hours: 3 hours

Dr Siham Gritly

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Nucleoside, Nucleotide & Nucleic acid

sugar base

sugar base

phosphate

sugar base

phosphate

sugar base

phosphate

sugar base

phosphate

• nucleoside • nucleotides

• nucleic acids

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DNA, RNA and the nucleobases

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• Deoxyribonucleotide; monomeric building block of DNA; a phosphate group and a nitrogenous base both bonded to deoxyribose

• Ribonucleotide; monomeric building block of RNA; a phosphate group and a nitrogenous base both bonded to ribose sugar

• Duplex; two complementary strands of DNA• Mutant; genetically altered species or cell

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• Nucleoside; nitrogenous base bonded to ribose or deoxyribose

• Nucleotide; monomeric building block of RNA and DNA; a phosphate group and a nitrogenous base both bonded to ribose or deoxyribose

• Nucleic Acids are Polynucleotides• Phosphodiester; two different alcohols

forming ester linkages with one phosphate ion

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• Replication; DNA synthesis• Template; a section of DNA which is being

replicated or transcribed; mRNA which is being translated

• Transcription; synthesis of RNA from DNA• Translation; synthesis of proteins from an

RNA template

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Nucleotides and Nucleic Acids

• Introduction;• Nucleic acids are macromolecules present in

all living cells in combination with protein with high concentration of basic amino acids to form nucleoproteins. (protamines and histones)

• Nucleic acids compounds carrying information

-- the genetic molecules (DNA and RNA) .

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• The nucleic acids are of two types• -1-deoxyribonucleic acid DNA• -2-ribonucleic acid RNA • DNA is present in the nuclei small amounts

present in the mitochondria• RNA is present in the cell cytoplasm (90%)

about 10% present in the nucleolus

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NucleotidesNucleoside phosphates

• Nucleotides are monomers of nucleic acids

• The nucleotides found in cells are derivatives of the heterocyclic highly basic, compounds, purine and pyrimidine present in DNA and RNA (nitrogenous bases)

Heterocyclic are ring compounds that contain both carbon atom and non-carbon atoms --mainly nitrogen atom.

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Nucleotide Structures of purine and pyrimidine Heterocyclic ring compounds

Nitrogenous Bases

Single six-sided ring pyrimidinesC4H4N2

Double ring purines (six- and five-sided) C5H4N4

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Types of nucleotide bases

• There are five major bases found in cells. • The derivatives of purine are called adenine

and guanine (found in both DNA & RNA) ,

• the derivatives of pyrimidine are called thymine, cytosine and uracil.

•

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The derivatives of purine ; adenine and guanine (found in both DNA & RNA) 1-Adenine 6-aminopurine, 2-Guanine 2-amino-6-oxypurine

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the derivatives of pyrimidine are thymine, cytosine and uracil. Cytosine- 2-oxy-4-aminopyrimidine, Uracil-n2,4-dioxypyrimidineThymine-2,4-dioxy-, 5-methyl

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• The common abbreviations used for these five bases are, A, G, T, C and U.

• Cytosine & Uracil in RNA• Cytosine and thymine in DNA • The nucleotide uridine is never found in DNA • thymine is almost exclusively found in DNA. • Thymine is found in tRNAs but not rRNAs nor

mRNAs

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Nucleotides mainly; Pentose sugar+ β-N-glycosidic bond+

phosphoryl group

• Derivative of purines and pyrimidines are nucleotides----contain mainly cyclyized sugar Pentose linked to nitrogen hetroatom by β-N-glycosidic bond additional to phosphoryl group esterified to hydroxy group of the sugar (β-D-ribose or β-D-2-deoxyribose)

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Nucleotides mainly;1-pentose sugar. 2-phosphate groups. 3-a nitrogeous base

• 1-5–carbon sugar component• Ribose• Deoxyribose

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5–carbon sugar component; Ribose and Deoxyribose Furanose structures

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• 2-Phosphate group Attached to the sugar's 5' carbon with a phosphodiester bond

• 3-Nitrogen Base component attached to the sugar's 1'carbon.

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Functions of Nucleotides

• Components of nucleic acids (which are long chains of nucleotides)

• ATP (Adonosine TriPhosphate) is central to energy metabolism

• GTP (Guanosine TriPhosphate) drives protein synthesis

• CTP (Cytidine Triphosphate) drives lipid synthesis • UTP (Uridine Triphosphate) drives carbohydrate

metabolism

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• Energy transport coenzymes (NAD+, NADP+, FAD+)

• Chemical intracellular messengers (e.g., Cyclic AMP, a cyclic nucleotide that carries messages from the cell membrane to molecules within the cell, to stimulate essential reactions. regulators of cellular metabolism and reproduction )

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Nucleosides

• Nucleoside consist of purine and pyrimidine bases and a sugar β-D-ribose or β-D-2-deoxyribose linked through a covalent β-N-glycosidic bond

• Therefore Nucleosides are Formed by Joining a Nitrogenous Base to a Sugar

• Base is linked via a β-N-glycosidic bond

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β-N-glycosidic bond linked nitrogen-9 of the purine base or nitrogen-1 of the pyrinidine base with

carbon1 of pentose sugar

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• The nucleosides of A, G, C,T, U are named • Adenine ---Adenosine• Guanine ----Guanisine• Cytosine ----Cytidine• Thymine ----Thymidine• Uracil -----Uridine• Purine nucleosides end “osine”• Pyrinidine ends in “idine” • Ribose sugar produced; ribonucleoside• 2-deoxyribose sugar produced;

deoxyribonucleosides

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• The nucleosides in DNA are called; deoxyadenosine,

• deoxyguanosine,• deoxycytidine, and thymidine, • the nucleosides in RNA are called;• adenosine, guanosine, cytidine, and uridine.• If the base is a purine, then the N-9 (nitrogen) is

bonded to the C-1' (carbon) of the sugar.• If the base is a pyrimidine, then the N-1 is bonded

to the C-1' of the sugar.

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Common nucleosides

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Glycosidic Bond Configurations

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The base can exist in 2 distinct orientations about the N-glycosidic bond. These conformations are identified as, syn and anti. It is the anti conformation that predominates in

naturally occurring nucleotides

Syn- adenosine anti-adenosine

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Nucleotides and nucleosides that are not part of DNA or RNA

the importance of free nucleotide

• Some nucleotides are not part of DNA or RNA but still play important roles in a cell.

• cyclic adenosine monophosphate (cAMP) is an intracellular signal: it communicates information from one part of the cell to another.

• Other nucleotides are coenzymes, which are molecules that help enzymes work properly (FAD, NAD).

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Adenosine triphosphate (ATP) Adenosine triphosphate (ATP) is a common and critical energy transfer molecule. The bonds that hold three phosphate groups to adenosine store energy. They form when energy is released and transfer that energy to other places in a cell.

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Adenosine Monophosphates (AMP)

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Nucleic acidpolynucletide

• the nucleic acids are polymers of subunits of monomers nucleotides.

• Nucleic acid; important substance that all cellular organisms use to store their genetic information.

• The most common nucleic acids are

deoxyribonucleic acid and ribonucleic acids

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The chemical linkage between nucleotide units in nucleic acids is a phosphodiester, which connects the 5’-hydroxyl group of one nucleotide to the 3’-hydroxyl group of the next nucleotide.

• Phosphodiester bonds are essential to all life, as they make up the backbone of each helical strand of DNA.

• In DNA and RNA, the phosphodiester bond is the linkage between the 3’ carbon atom of one sugar molecule and the 5’ catbon atom of another;

• the sugar molecules deoxyribose in DNA• and ribose in RNA.• Hydrolysis of phosphodiester bonds can be

catalyzed by the action of phosphodiesterases

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Sequences of RNA and DNA structuresThe chemical linkage between monomer units in

nucleic acids is a phosphodiester

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phosphodiester, connects the 5’-hydroxyl group of one nucleotide to the 3’-hydroxyl group of the next nucleotide.

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Formation of phosphodiester bonds Formed by Polymerase and Ligase activities

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classes of nucleic acids1-Deoxyribonucleic acid DNA

• Deoxyribonucleic acid (DNA) is a

nucleic acid containing the genetic

instructions used in the development

and functioning of all known living organisms (with the exception of RNA viruses).

• The DNA segments carrying this genetic information are called genes .

• Genes (specific regions of DNA molecules) contain the hereditary information of an organism.

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• When organisms reproduce The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription.

• Within cells DNA is organized into long structures called chromosomes, (packaged form of the DNA).

• During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes (46).

• Within the chromosomes, chromatin proteins such as histones compact and organize DNA.

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DNA structure and function

• DNA structure is the well-known double helix formed by Watson-Crick base-pairing of C with G and A with T.

• This is known as B-form DNA, and is the most favorable and common state of DNA;

• its highly specific and stable base-pairing is the basis of reliable genetic information storage.

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Structure of DNA naturally occurring DNA molecules are double-

stranded

Watson-Crick model for the structure of DNA

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Tertiary Structure of DNA: Supercoils. Each cell contains about two meters of DNA. DNA is “packaged” by coiling around a core of proteins known as histones. The DNA-histone assembly is called a nucleosome. Histones are rich is lysine and arginine residues

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the Watson-Crick model

• James Watson and Francis Crick proposed a model for the structure of DNA.

• This model predicted that DNA would exist as

a helix of two complementary antiparallel strands, wound around each other in a rightward direction and stabilized by H-bonding between bases in adjacent strands.

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• They proposed that in any given molecule of DNA,;-• the concentration of adenine (A) is equal to

thymine (T) • and the concentration of cytidine (C) is equal to

guanine (G). • This means that A will only base-pair with T, and C

with G. According to this pattern, known as Watson-Crick base-pairing, the base-pairs composed of G and C contain three H-bonds, whereas those of A and T contain two H-bonds. This makes G-C base-pairs more stable than A-T base-pairs.

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Base pairing model

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Base pairs are stabilized by H-bonding

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the base-pairs composed of G and C contain three H-bonds, whereas those of A and T contain two H-

bonds.

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Watson-Crick base-pairing of C with G and A with T

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Complementarity of strands in the DNA double helix

-Adenine (A) and thymine (T) always pair together (A–T),-cytosine (C) and guanine (G) always pair together (C–G).

In other words, A and T are complementary bases, as are C and G.

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Replication of DNA as suggested by

Watson and Crick

Replication: process by which DNA is copied itself

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Two polynucleotide strands, running in opposite directions (anti-parallel) and coiled around each other in a double helix.The strands are held together by complementary hydrogen- bonding between specific pairs of bases

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REPLICTION, TRANSCRIPTION AND TRANSLATION

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Function of DNA

• 1-store of genetic information;• genetic information is the source of

information for the synthesis of all protein molecules. The information is copied or transcribed into RNA molecules

• Proteins are then synthesized in the process involving the translation of the RNA

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• 2-DNA provides the inherited information by the daughter cell. DNA provide template for the replication of information into daughter DNA molecule

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2-Ribonucleic acid RNA

• Ribonucleic acid RNA is a long unbranched macromolecules consisting of nucleotides joined by 3’ to 5’ phosphodiester bonds. It is the same as DNA but it possesses different characteristic

• RNA differ from DNA in that it is a single strand do not contain regions of double helical structure

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• RNA contain ribose sugar instead of 2-deoxyribose that present in DNA

• contain four major bases• 1-purine bases;-Adenine and Guanine• 2-pyrimidin bases;- Cytosine and Uracil• RNA contain Uracil instead of thymine• RNA pairs Adenine with Uracil and Cytosine

with Guanine

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Structure of RNA RNA molecules are single-stranded

RNA contain Uracil instead of thymineRNA pairs Adenine with Uracil and Cytosine with Guanine

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Ribonucleic acid (RNA) functions

• Ribonucleic acid (RNA) functions in converting genetic information from genes into the amino acid sequences of proteins.

RNA translates the DNA message to a format that can be read by ribosomes, or the cellular organelles that assemble proteins (process known as translation).

RNA also plays a role in engage the correct amino acids to the protein meeting sites.

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types of RNA

• The three universal types of RNA include • 1-transfer RNA (tRNA), transfer RNA serves as the

carrier molecule for amino acids to be used in protein synthesis, and is responsible for decoding the mRNA.

• 2-messenger RNA (mRNA), messenger RNA acts to carry genetic sequence information between DNA and ribosomes, directing protein synthesis

• 3-ribosomal RNA (rRNA). ribosomal RNA is a major component of the ribosome, and catalyzes peptide bond formation.

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RNA & DNA structures

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PHOSPHODIESTER BOND LINK NUCLETIDES

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references

Murry K. Robert, Granner K. daryl, Mayes A. peter, Rodwell W. Victor (1999). Harpers Biochemistry. Appleton and Lange , twent fifth edition

• A. Burtis, Edward R. Ashwood, Norbert W. Tietz (2000), Tietz fundamentals of clinical chemistry

• Maton, Anthea; Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David LaHart, Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. pp. 52–59

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references

• Nelson DL, Cox MM (2005). Lehninger's Principles of Biochemistry (4th ed.). New York, New York: W. H. Freeman and Company.

• Matthews, C. E.; K. E. Van Holde; K. G. Ahern (1999) Biochemistry. 3rd edition. Benjamin Cummings.

• Naik Pankaja (2010). Biochemistry. 3ed edition, JAYPEE

• Maitland, Jr Jones (1998). Organic Chemistry. W W Norton & Co Inc (Np). p. 139. ISBN 0-393-97378-6.

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Pentose sugar

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