Dr. Aga Syed SameerCSIR LecturerDepartment of Biochemistry,Medical College,Sher-I-Kashmir Institute of Medical Sciences, Bemina, Srinagar, Kashmir, 190018. India.
NUCLEIC ACIDSCHEMISTRY
• Discovered first in PUS cells and salmon sperm cells by Friedrich Miescher
• Named as nuclein because of its source
• R. Altmann designated it as nucleic acid because of its acidic nature
Introduction
• Are important biomolecules responsible for the very existence of living beings
• Act as molecular repositories and transmitters for genetic information
• Biopolymers of mononucleotides which are held together by 3’-5’ phosphate bridges
Introduction
• Building blocks of nucleic acids (RNA, DNA)
• Analogous to amino acid role in proteins
• Energy currency in cellular metabolism (ATP: adenosine triphosphate)
• Allosteric effectors in various enzymes (ATP, AMP, ADP, cAMP: cyclic Adenosine Monophosphate, cGMP, NAD)
• Structural components of many enzyme cofactors (NAD: nicotinamide adenine dinucleotide)
• Oxido-Reducing agents (NADH: nicotinamide adenine dinucleotide)
• Serving as activated intermediates in numerous biosynthetic reactions
• Serving as mediators of numerous important cellular processes such as second messengers in signal transduction events (cAMP: cyclic Adenosine Monophosphate)
Introduction
• Are made up of:
• Carbon
• Hydrogen
• Oxygen
• Nitrogen
• Phosphorus
Chemical Composition
• Structurally nucleic acids are polymers of mononuleotides
• Polymer is possible due to phosphodiesterlinkages
• Each mononucleotide is made of three components
• Sugar Base
• Phosphate Ion
• Nitrogen Base
Chemical Composition
• Sugar
• Five carbon aldose (pentose) present in furanoseconformation
• Either as ribosesugar or as deoxyribose
Chemical Composition
• Phosphate
• As H3PO4.
• As it contains three monovalent hydroxyl groups it can form three bonds but in nucleic acids it form two bonds with sugar moiety.
• One bond is formed between the 3’ hydroxyl group of the ribose and other with the 5’ hydroxyl of the second ribose.
• In acts as the linker between the two adjacent ribose (or deoxyribose) moieties.
Chemical Composition
• Nitrogen Base
• Are of the derivatives of the two types of molecules: Pyrimidines and Purines
• Pyrimidine is a heterocyclic six atom ringed molecule. Purine is a heterocyclic double ringed molecule which contains a pyrimidine and an imidazole ring
• The common purine derivatives are Adenine & Guanine, and pyrimidine derivatives are Thymine, Cytosine & Uracil
Chemical Composition
• Pyrimidines
• Cytosine: 4-amino 2-oxypyrimidine (C4H5ON3 ; mw= 111.12) is found in DNA and RNA.
• Thymine: 5-methyl 2,4-dioxypyrimidine (C5H6O2N2 ; mw= 126.13) is found almost exclusively in DNA.
• Uracil: 2,4-dioxypyrimidine (C4H4O2N2 ; mw= 112.10) is found almost exclusively in RNA.
Chemical Composition
• Purines
• Adenine: 6-aminopurine (C5H5N5 ; mw= 135.15) is found in DNA and RNA.
• Guanine: 2-amino 6-oxypurine (C5H5ON5 ; mw= 151.15) is found in DNA and RNA.
Chemical Composition
• Nucleosides
• Are composed of N-base attached to a ribose or deoxyribose moiety through a covalent bond at carbon 1.
• This bond is formed by the elimination of a molecule of water resulting in the formation of a glycosidicbond.
• Nucleosides containing ribose are called ribonucleosides & those possessing deoxyribose as deoxy ribonucleosides.
Chemical Composition
• Nucleosides
• Pyrimidines are connected to the sugar moiety through N1 (C1-N1)
• Purines remain connected through N9 (C1-N9).
• Glycosidic bonds in nucleosides and nucleotides are always of the β-configuration
Chemical Composition
• Nucleosides
Chemical Composition
• Nucleosides
• Pyrimidine nucleosides favor the anti conformation
• For pyrimidines in the syn conformation: the oxygen substituent at position C-2 lies immediately above the furanose ring
• Purine nucleosides can adopt either the syn or anti conformation
Chemical Composition
• Nucleotides
• Nucleotides are composed of a sugar, a phosphate, and N-base
• They are actually phosphoric acid esters of nucleosides.
• These occur either in the free form or as the monomer in nucleic acids.
• In an isolated nucleotide the phosphate moiety is attached to the nucleoside at the carbon 5 of the sugar through ester linkage.
Chemical Composition
• Mono-Nucleotides
Chemical Composition
• Di/Tri-Nucleotides
Chemical Composition
• Cyclic-Nucleotides
Chemical Composition
Chemical Composition
• The ribonucleoside containing adenine is called adenosine. The deoxyribonucleoside containing adenine is called deoxyadenosine.
• The ribonucleoside containing guanine is called guanosine. The deoxyribonucleoside containing guanine is called deoxyguanosine.
• The ribonucleoside containing cytosine is called cytidine. The deoxyribonucleoside containing cytosine is called deoxycytidine.
• The deoxyribonucleoside containing thymine is called thymidine.
• The ribonucleoside containing uracil is called uridine. The deoxyribonucleoside containing uracil is called deoxyuridine
Chemical Composition
Chemical Composition
• ATP: Acts as cellular currency of energy and it concentration determines the cellular capability for a certain job
• GTP: Is necessary for the energy input for the synthesis of Proteins during translation process
• cAMP: Is the foremost cellular messenger for the hormones via which they mediate their action
• cGMP: Act as a second messenger for many hormones especially in nitric oxide signal transduction
• NAD+/NADP+: Act as cellular reducing agents without which synthesis processes will halt
Important ones
• Biochemistry: Lehningers by Nelson & Cox – W.H. Freeman
• Biochemistry by Pamela C Champe – Lippincot WW
• Medical Biochemistry by Chaterjee & Shinde – Jay Pee
• Biomedical Biochemistry by Prem Prakash Gupta – CBS
• Biochemistry: Harpers by Robert K. Murray et al - Tata McGraw Hill
• Biochemistry by Harton – Bartlett & Jones
• Biochemistry For Dummies by John T Moore et al - Tata McGraw Hill
• Biochemistry: Instant Notes by B.D. Hames et al – Viva Books
• Molecular Biology by Lodish, Baltimore et al – W.H. Freeman
• Molecular Biology: Instant Notes by P.C. Turner et al – Viva Books
• Genetics by E.J. Gardner – J. Wiley & Sons
• Genetics: Instant Notes by P.C. Winter et al – Viva Books
Books
Questions??
Next Lecture Polymers of Nucleotides
(DNA)