Low Rate Call Girls Pune Esha 9907093804 Short 1500 Night 6000 Best call girl...
NUCLEIC ACIDS biochemistry DR.MAGEJA.pdf
1.
2. Nucleotides
Nucleotideshave a variety of roles in cellularmetabolism
They are the energy currencyin metabolicreactions-function ofATP
GTP,UTP,CTP are sources of energy in certain metabolicpathways.
There are componentsof an array of enzyme cofactors and metabolic
intermediates e.g NAD,NADP,FAD and CoenzymeA contain nucleotides.
Act as essential chemical links in the responseof cells to hormones e.g
cAMP acts as a second messenger inside the cell for many peptide
hormones e.g glucagon and epinephrineand cGMP acts as a cellular
regulator.
Some nucleotidesare important regulators for many metabolicreactions.
Nucleotidesact as carriers of activated intermediates such as :
UDP-glucose in synthesis of glycogen
CDP-cholinein the synthesis of phospholipids
GDP-mannose in the synthesis of glycoproteins.
3. Nucleotides
they are the constituentsof nucleic acids:deoxyribonucleicacid (DNA)
and ribonucleicacid (RNA), the molecularrepositories of genetic
information.
Synthetic analogs of naturallyoccuring nucleotides
These compoundsinhibit the growth of cancer cells by:
• Inhibiting their enzyme activity or
• Inhibiting the synthesis of either DNA or RNA
e.g.5 fluorouracil
Allopurinol,apurineanalog is widely used in the treatment of gout.
4. Nucleic acids
A most remarkable propertyof living cells is their ability to produceexact
replicas of themselves.
This is due to the cells containingfact that all the instructionsneeded for
making the completeorganism of which they are a part.
Nucleic acids are the moleculeswithin a cell that are responsiblefor these
amazing capabilities.
The structureof every protein, and ultimately of every biomoleculeand
cellularcomponent,is a productof information programmed into the
nucleotidesequenceof a cell’s nucleicacids
The ability to store and transmit genetic information from one generation to
the next is a fundamental condition for life
5. Classes of nucleic acids
There are two major classes of nucleicacids
o Deoxyribonucleicacid (DNA): carrier of genetic information
o Ribonucleicacid (RNA): an intermediate in the expression of genetic
information and other diverse roles
DNA = permanent repositorywhich stores master plans
RNA = temporary repository → “copy” of certain plans
Working RNAs (e.g.rRNA).
AdapterRNAs (e.g. tRNA)
Intermediary RNAs (e.g. mRNA).
Protein = working machinery.
7. Nucleotides are the monomeric units
for nucleic acids
Nucleotides are made up of three
structural subunits
1. Sugar: ribose in RNA,deoxyribose
in DNA
2. Heterocyclic base
3. Phosphate
RNA: polar ribose phosphate
backbone
DNA: polar deoxyribose phosphate
backbone
(no 2′-hydroxyl)
Nucleotides joined by 3′,5′-
phosphodiester linkages
Nitrogenous bases – side chains
8. Bases
The bases of DNA and RNA are
heterocyclic(carbon-and
nitrogen-containing) aromatic
rings
Adenine (A) and guanine (G) are
purines, bicyclic structures(two
fused rings), whereas cytosine
(C), thymine (T) and uracil (U)
are monocyclic pyrimidines.
N-β- glycosyl bond:1′ carbon of
ribose and N9 of Pur base (A, G)
or N1 of Pyr base (C,T, U)
Pur or Pyr base + ribose =
nucleoside
9. Nucleosides, Nucleotides, and Nucleic
Acids
Nucleosides. N-Glycosides of a purine or pyrimidine heterocyclic base and a
carbohydrate .
The C-N bond involves the anomeric carbon of the sugar.
The chemical linkage between monomer units in nucleic acids is a phosphodiester
10. Chemistry of nucleotide components
Phosphategroup
o Strong acid
o pKa ~1 for primary ionization,~6
for secondary
Purine/Pyrimidine(pKa ~2.4-9.5)
o Weak tautomericbases
o Isomers differing in position of H
o atoms & doublebond.
o Less stable imino & enol forms
o found in special base interactions.
Conjugateddouble-bonds
o Resonanceamong ring atoms
o Absorb UV light
12. Chemical stability of polynucleotides
(contribution of the ribose ring)
Hydrolysis of DNA and RNA is
thermodynamically favourable but
very slow.
Acid-labile bond (purine glycosidic
linkage in DNA but not RNA
Base-labile bond (PDE bond in
RNA but not DNA)
Nucleases (endo & exo,specific &
non-specific)
promote rapid hydrolysis of PDE
bonds in DNA or RNA.
Dehydration-resistant (e.g.DNA in
fossils) but water content (level of
hydration) affects secondary
structure
15. Phosphodiesters, Oligonucleotides, and
Polynucleotides
The successive nucleotidesof both DNA
and RNA are covalently linked through
phosphate-group“bridges,” in which the 5-
phosphategroup of one nucleotide unit is
joined to the 3-hydroxyl group of the next
nucleotide,creating a phosphodiester
linkage
A short nucleic acid is referred to as an
oligonucleotide.
The definition of “short”is somewhat
arbitrary, but polymers containing50 or
fewer nucleotidesare generally called
oligonucleotides.
A longer nucleic acid is called a
polynucleotide.
19. Structure of DNA
DNA is composed of four
nucleotides, each containing:
adenine, cytosine, thymine, or
guanine.
It consist of two polynucleotide
strands, runningin opposite
directions(anti-parallel)and
coiled around each otherforming
right handed doublehelix
The strands are held together by
complementaryhydrogen-
bonding between specific pairs of
bases. Adenine pairs with
Thiamine and Guanine pairs
with Cytosine
20. Primary and secondary structure of
DNA
Primary structure - The sequence
of bases in the nucleicacid chain
gives the primary structureof
DNA
Secondarystructure –
Double helix (which is the regular
repeating conformation)
5’-C-A-C-G-T-C-T-A-G-T-C-G-A-
C-3’
21. Tertiary Structure:DNA can occur in different 3-
Dimensionalforms
DNA is a remarkably flexible molecule
Considerablerotation is possible arounda number of bonds in the sugar
phosphatebackbone
Thermal & humidity fluctuationsand changes in the conce of salt/alcoholcan
producebending, stretchingand unpairing of the strands
Many significant deviations of the Watson and Crick model may play important
roles in metabolism
The structuralvariations do not affect the key propertiesof DNA defined by
Watson and Crick
i.e. strand complimentarity, antiparallel strandsand the requirement for A=T and
G=C base pairs
The Watson and Crick structureis also referred to as B form DNA or B –DNA
Two structuralvariants that have been well characterised are the A and Z forms
22. B-DNA
• The structureidentified by Watson and
Crick, and is known as B-DNA
• It is a right handed doublehelix
• The negativelycharged sugar–phosphate
backbones of the moleculesare on the
outside, and the planar bases of each strand
stack one above the other in the centerof
the helix
• Between the backbonestrands run the
major and minor grooves, which also
follow a helical path.
• There are around 10 base pairs per turn
in the DNA double helix
• The two strands are oriented in opposite
directions(antiparallel)in terms of their
5→3’direction and, most crucially, the two
strands are complementaryin terms of
sequence
24. A-DNA
DNA can be induced to form an
alternative helix, known as the
A-form
The A-form is right-handed,
like the B-form,
However it has a wider, more
compressed structure in which
the base pairs are tilted with
respect to the helix axis, and
actually lie off the axis
It has 11 base pairs per turn in
the DNA double helix
The major importance of the A-
form is that it is the helix
formed by RNA and by DNA-
RNA hybrids
25. Z-DNA
Z-form DNA is a more radical departure
from the B structure;the most obvious
distinction is the left handed helical
rotation.
There are 12 base pairs per helical
turn, and the structureappears more
slenderand elongated.
The DNA backbonetakes on a zigzag
appearance.
Certain nucleotidesequencesfold into
left handed Z helices much more readily
than others
Prominent examples are sequencesin
which pyrimidines alternatewith
purines, especially alternatingC and G
(such as 5´-CGCGCG-3´, with the same
in the other strand
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37. Packaging of DNA in cells
Each cell contains
about two meters of DNA. DNA
is “packaged” by coiling around
a core of proteinsknown as
histones.
The DNA-histone
assembly is called a nucleosome.
Histones are rich is lysine and
arginine residues.
This is tertiary structureof DNA !
38.
39.
40.
41. RNA
RNA normallyoccurs as a single-strandedmolecule and hence it does not
adopt a long regular helical structurelike double-strandedDNA
RNA instead forms relatively globular conformations, in which local regions of
helical structureare formed by intra-molecular hydrogen bonding and base
stacking within the single nucleic acid chain
These regions can form where one part of the RNA chain is complementaryto
another
This conformationalvariabilityis reflected in the more diverseroles of
RNAin the cell, when compared with DNA
43. RNA have diverse roles
RNA structuresrange from short small nuclearRNAs, which help to
mediate the splicingof pre-mRNAs in eukaryotic cells to large rRNA
molecules, which form the structural backboneof the ribosomes and
participatein the chemistry of protein synthesis
Messenger RNAs (mRNAs) are intermediaries, carrying genetic
information from one or a few genes to a ribosome, where the
correspondingproteinscan be synthesized.
Transfer RNAs (tRNAs) are adapter moleculesthat faithfully translatethe
information in mRNA into a specific sequenceof amino acids.
Small nuclearRNA
Small RNAs, generally less than 300 nucleotideslong and rich in uridine
(U), are localized in the nucleoplasm(snRNAs) and nucleolus(snoRNAs)
of eukaryotic cells. There they take part in RNA processing, such as intron
removal during eukaryotic mRNA splicing and posttranscriptional
modification that occurs during production of mature rRNA. See Intron
CatalyticRNA
RNA enzymes, or ribozymes, are able to catalyze specific cleavage or
joining reactions either in themselves or in othermolecules of nucleicacid.
See Catalysis, Ribozyme
44. RNA
Splicing of mRNA: Splicing is a modification of an RNA after
transcription, in which introns(nonessential part of the code)are removed
and exons(essential part of the code) are joined.
Also the UTRs, non-codingparts of exons at the ends of the mRNA is also
removed.