Nucleic acid chemistry na 01

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


• Sugar

• Five carbon aldose (pentose) present in furanoseconformation

• Either as ribosesugar or as deoxyribose


• 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.


• 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


• 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.


• 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.


• 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.


• 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


• Nucleosides


• 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


• 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.


• Mono-Nucleotides


• Di/Tri-Nucleotides


• Cyclic-Nucleotides


• 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


• 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)

Nucleic acid chemistry na 01

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