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7/31/2019 Nucleotides Chemistry and Metabolism
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NUCLEOTIDENUCLEOTIDEMETABOLISMMETABOLISM
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NUCLEOTIDES
Nucleotides are essential for all cells They are main building blocks of DNA and
RNA and without them proteins cannot besynthesized or cells cannot proliferate
Nucleotides serve as carriers of activatedintermediates in the synthesis of somemacromolecules
They are structural components of essentialco-enzymes such as coenzyme A, FAD, NAD,and NADP
Nucleotides play an important role as
energy currency in the cell
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Types Of Bases:
1. Purine Bases
2. Pyrimidine bases
3. Unusual bases
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NUCLEOSIDES:
Ribose Sugar (Pentose) + Nitrogenous Base
NUCLEOTIDES:
Ribose Sugar + Nitrogenous Base + Phosphoryl Group
NUCLEIC ACIDS:
polymer of nucleotides
storage & expression of genetic
information
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TYPES OF NUCLEOSIDESTYPES OF NUCLEOSIDES
Ribonucleosides:- Contains Ribose Sugar
Deoxyribonucleosides:-
Contains Deoxyribose sugar
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TYPES OF NUCLEOTIDESTYPES OF NUCLEOTIDES
Ribonucleotides:- Contains Ribose Sugar
Deoxyribonucleotides:-
Contains Deoxyribose sugar
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TYPES OF NUCLEIC ACIDSTYPES OF NUCLEIC ACIDS
RNA (Ribonucleic acid) :- Polymer of Ribonucleotides
DNA (Deoxyribonucleic acid):-
Polymer of Deoxyribonucleotides
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PURINE BASES
1. ADENINE ( A )
2. GUANINE ( G )
Present In Both DNA & RNAPresent In Both DNA & RNA Larger Heterocyclic BasesLarger Heterocyclic Bases
Contain 9 AtomsContain 9 Atoms 4 N + 5 C4 N + 5 C
Counterclockwise numbering ofCounterclockwise numbering of
atoms in ringatoms in ring
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H
C
6N 1
C 2
N 3H
C 4
C 5
N 7
CH 8
N
H 9
STRUCTURE OF PURINESTRUCTURE OF PURINE
1 2 3 - 4 5 6 - 7 8 9
N C N - C C C - N C N
Sum Up Structure As
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ADENINEADENINE
(A)(A)
NH2
N
N
N
N
H
6
6 - Aminopurine
GUANINEGUANINE
(G)(G)O
HN
N
N
N
HNH2
2
6
2 Amino -6 - oxypurine
PURINE
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2.PYRIMIDINE BASES
1. THYMINE (T)
2. CYTOSINE (C)
3. URACIL (U)
RNA = Cytosine & UracilDNA = Cytosine & Thymine
Smaller Heterocyclic Bases
Contain 6 Atoms ---- 2 N + 4C
Clockwise numbering of
atoms in the ring
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H
C 4
N 3
HC 2
N1CH6
CH5
Structure Of PyrimidineStructure Of Pyrimidine
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O
HN
O
NH
CH3
Thymine (T)Thymine (T)
(5-methyl Uracil)(5-methyl Uracil)
4
5
2
Uracil (U)Uracil (U)
2,4 Dioxy2,4 Dioxy
pyrimidinepyrimidine
O
HN
O
N
H
2
4
O
N
NH2
N
H
Cytosine (C)Cytosine (C)
(2-oxy,4-amino pyrimidine)
4
2
PYRIMIDINES
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Linkage Between Base &Linkage Between Base &
Ribose SugarRibose Sugar
N Glycosidic
Bond
1/ C linked
to N-1 ofPyrimidineand N-9 ofpurine base
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Cytidine (cytosine + ribose sugar)
1
N
OH
OH OH
N
NH2
O
1/
2/3/
4/
5/
2
3 4
5
6
O
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Nucleic Acid
Nucleosides If a sugar, either ribose or 2-deoxyribose,
is added to a nitrogen base, the resultingcompound is called a nucleoside. Carbon 1of the sugar is attached to nitrogen 9 of apurine base or to nitrogen 1 of a pyrimidinebase.
Adenosine Guanosine Inosine - the base in inosine is
hypoxanthine Uridine Thymidine Cytidine
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Nucleic Acid Nucleotides
Adding one or more phosphates to the sugar
portion of a nucleoside results in anucleotide. Generally, the phosphate is inester linkage to carbon 5' of the sugar.
AMP = adenosine monophosphate = adenylic
acid CDP = cytidine diphosphate
dGTP = deoxy guanosine triphosphate
dTTP = deoxy thymidine triphosphate (TTP) cAMP = 3'-5' cyclic adenosine
monophosphate
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Polynucleotides
Nucleotides are joined together by 3'-5'phosphodiester bonds to formpolynucleotides. Polymerization ofribonucleotides will produce an RNA
while polymerization ofdeoxyribonucleotides leads to DNA.
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Deoxyribonucleic acid DNA is a polymer of
deoxyribonucleotides
It is found in chromsomes,
mitochondria and chloroplasts Primary structure
It is number and sequence of
different deoxyribonucleotides in itsstrands joined by phosphodiesterlinkage
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ADENINEADENINE
(A)(A)
NH2
N
N
N
N
H
6
6 - Aminopurine
GUANINEGUANINE
(G)(G)O
HN
N
N
N
HNH2
2
6
2 Amino -6 - oxypurine
PURINE
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O
HN
O
NH
CH3
Thymine (T)Thymine (T)
(5-methyl Uracil)(5-methyl Uracil)
4
5
2
Uracil (U)Uracil (U)
2,4 Dioxy2,4 Dioxy
pyrimidinepyrimidine
O
HN
O
N
H
2
4
O
N
NH2
N
H
Cytosine (C)Cytosine (C)
(2-oxy,4-amino pyrimidine)
4
2
PYRIMIDINES
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1
N
OH
OH OH
N
NH2
O
1/
2/3/
4/
5/
2
3 4
5
6
O
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B-DNA Adjacent nucleotides in each chain are
rotated by 34.6 relative to each other
One turn approximately completes after
every10.4 base pairs One turn spans the distance of 3.4 nM
This is called pitch of DNA
Diameter of double helix is 2.37nM
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A-DNA When B-DNA crystals are dried or when
salt content of the crystals is lowered,the long thin DNA molecule becomes
short, stubby molecule and is called A-DNA
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Z-DNA It is longer and thinner than B-DNA
It has left handed helix
One complete turn has 12 base pairs
Diameter is 1.84 nM
The major groove is no more but aconvex surface
Minor groove is in form of a cleft
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Ribonucleotides m-RNA
hn-RNA
PRE-mRNA
r-RNA
t-RNA
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Messenger RNA 5-10% of cellular RNA is a molecule ofRNA that encodes a
chemical "blueprint" for a protein
product. mRNA is transcribed from a DNA
template, and carries codinginformation to the sites of
protein synthesis, the ribosomes. In the ribosomes, the mRNA is
translated into a polymer ofamino acids: a protein
http://en.wikipedia.org/wiki/RNAhttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Transcription_(genetics)http://en.wikipedia.org/wiki/DNAhttp://en.wikipedia.org/wiki/Protein_synthesishttp://en.wikipedia.org/wiki/Ribosomeshttp://en.wikipedia.org/wiki/Translation_(genetics)http://en.wikipedia.org/wiki/Amino_acidshttp://en.wikipedia.org/wiki/Amino_acidshttp://en.wikipedia.org/wiki/Translation_(genetics)http://en.wikipedia.org/wiki/Ribosomeshttp://en.wikipedia.org/wiki/Protein_synthesishttp://en.wikipedia.org/wiki/DNAhttp://en.wikipedia.org/wiki/Transcription_(genetics)http://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/RNA7/31/2019 Nucleotides Chemistry and Metabolism
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Transfer RNA 10-15% of cellular RNA
Transfers amino acids to the ribosomesfor protein synthesis
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Ribosomal RNA 75-80% of cellular RNA
Found in ribosomes which are the sitesof protein synthesis
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SYNTHESIS OF PURINE NUCLEOTIDES
DE NOVO SYNTHESIS
SALVAGE PATHWAY FOR PURINES
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H
C
6N 1
C 2
N 3H
C 4
C 5
N 7
CH 8
N
H 9
STRUCTURE OF PURINESTRUCTURE OF PURINE
1 2 3 - 4 5 6 - 7 8 9
N C N - C C C - N C N
Sum Up Structure As
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SOURCE OF4 NITROGEN ATOMS
GLUTAMINE 2 N ( 3, 9 )
GLYCINE 1 N ( 7 )
ASPARTATE 1 N ( 1 )
SOURCE OF 5 CARBON ATOMS N10 FORMYLE THF 2 C ( 2, 8 )
GLYCINE 2 C ( 4, 5 )
CO2 1 C ( 6 )
SUBSTRATE TO START:Ribose 5 /- Phosphate (HMP-Shunt)
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Sources of the individual atoms in the
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C
C
CC
N
N
Amide nitrogenof glutamine
Aspartic acid
CO2
Sources of the individual atoms in the
Pyrimidine ring
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Source Of 2 Nitrogen
AtomsGlutamine 1 N ( 3 )
Aspartic Acid 1 N ( 1 )
Source of 4 carbon atoms
Aspartic Acid 3 C
( 4,5,6 )
CO 1 C ( 2 )
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Pyrimidine Biosynthesis
PRECURSORS1). PRPP (donor of Ribose-5-PO4)
2). Glutamine
3). CO24). Aspartate
KEY ENZYMECarbamoyl Phosphate Synthase II
(Cytosolic )
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Six membered Pyrimidine ring issynthesized and then attached to
Ribose 5 phosphate, unlike purines Glutamine and aspartate are required
for both purine and pyrimidine
synthesis
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SALVAGE PATHWAY FOR
PURINES
DEFINITION
Free purine bases obtained due toBreakdown of nucleic acids or from the
diet
and not degraded, can be reconverted into
Nucleoside triphosphates (nucleotides)and used by the Body.
Requires less energy
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ENZYMES REQUIRED
1. Adenine PhosphoribosylTransferase
( APRT )
2. Hypoxanthine GuaninePhosphoribosyl Transferase
( HGPRT)
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SOURCE OF RIBOSE 5 PHOSPHATE:
Phosphoribosyl Pyrophosphate( PRPP )
SUBSTRATES FOR SALVAGEPATHWAY
HYPOXANTHINE
GUANINE
REACTIONS OF SALVAGEREACTIONS OF SALVAGE
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PATHWAYPATHWAY
ADENIN
E
AMP
PRPP PPi
APRTAPRT
GUANINE
GMP
PRPP PPi
HGPRTHGPRT
HYPOXANTHINE IMP
PRPP PPi
HGPRTHGPRTLESCH NYHANLESCH NYHAN
SYNDROMESYNDROME
Salvage of Pyrimidine
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Substrate Enzyme
Uridine
Uridine Cytidine kinaseCytidine
Deoxycytidine Deoxycytidine kinase
Thymidine Thymidine kinase
Salvage of Pyrimidine
ATP ADP
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Cytidine
ATP
ATP
ATP
ATP
ADP
ADP
ADP
ADP
Uridine UMP
CMP
Thymidine
Deoxycytidine
TMP
dCMP
Uridine-Cytidine Kinase
Thymidine Kinase
Deoxycytidine Kinase
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Metabolic disorders of nucleotides
Leisch-Nehan Syndrome
Gout
Orotic aciduria
Xanthineuria
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Degradation of purine nucleotides
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Normal plasma uric acid level:
Men: 3 9 mg/dlWoman: 2.5 7.5 mg/dl
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Degradation of Pyrimidines
Produces NH4+ and thus urea formation
Unlike purines, its ring structure can beopened/cleaved into highly water
soluble structures like - Alanine
(a precursor of acetyl-CoA)
-Aminoisobutyrate(a precursor of Succinyl-CoA)
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CPS I CPS IICellular
location
mitochondria cytosol
Pathwayinvolved
Urea cycle Pyrimidinesynthesis
Source of
Nitrogen
Ammonia -Amide group of
glutamine
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Digestion and absorption ofnucleotides Nucleotidases break down nucleotides
(such as the thymidinemonophosphate) into nucleosides (such as thymidine)and phosphate.
The nucleosides, in turn, aresubsequently broken down in the lumenof the digestive system by
nucleosidases into nitrogenous basesand ribose or deoxyribose
http://en.wikipedia.org/wiki/Thymidine_monophosphatehttp://en.wikipedia.org/wiki/Thymidine_monophosphatehttp://en.wikipedia.org/wiki/Thymidine_monophosphatehttp://en.wikipedia.org/wiki/Thymidine_monophosphatehttp://en.wikipedia.org/wiki/Thymidine_monophosphatehttp://en.wikipedia.org/wiki/Nucleotidehttp://en.wikipedia.org/wiki/Thymidine_monophosphatehttp://en.wikipedia.org/wiki/Thymidine_monophosphatehttp://en.wikipedia.org/wiki/Thymidine_monophosphatehttp://en.wikipedia.org/wiki/Thymidinehttp://en.wikipedia.org/wiki/Lumen_(anatomy)http://en.wikipedia.org/wiki/Nucleosidasehttp://en.wikipedia.org/wiki/Nucleosidasehttp://en.wikipedia.org/wiki/Lumen_(anatomy)http://en.wikipedia.org/wiki/Thymidinehttp://en.wikipedia.org/wiki/Thymidine_monophosphatehttp://en.wikipedia.org/wiki/Thymidine_monophosphatehttp://en.wikipedia.org/wiki/Thymidine_monophosphatehttp://en.wikipedia.org/wiki/Nucleotidehttp://en.wikipedia.org/wiki/Nucleotidase7/31/2019 Nucleotides Chemistry and Metabolism
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Chromosomes A chromosome is an organized
structure ofDNA and protein found incells.
It is a single piece of coiled DNAcontaining many genes,regulatory elements and othernucleotide sequences.
Chromosomes also contain DNA-boundproteins, which serve to package theDNA and control its functions.
http://en.wikipedia.org/wiki/DNAhttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Cell_(biology)http://en.wikipedia.org/wiki/Genehttp://en.wikipedia.org/wiki/Regulatory_sequencehttp://en.wikipedia.org/wiki/Genetic_sequencehttp://en.wikipedia.org/wiki/Genetic_sequencehttp://en.wikipedia.org/wiki/Regulatory_sequencehttp://en.wikipedia.org/wiki/Genehttp://en.wikipedia.org/wiki/Cell_(biology)http://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/DNA7/31/2019 Nucleotides Chemistry and Metabolism
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Chromatin In eukaryotes, nuclear chromosomes
are packaged by proteins into acondensed structure called chromatin.
http://en.wikipedia.org/wiki/Chromatinhttp://en.wikipedia.org/wiki/Chromatin7/31/2019 Nucleotides Chemistry and Metabolism
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Genes A gene is a molecular unit ofheredity
of a living organism.
It is a name given to some stretches of
DNA and RNA that code for apolypeptide or for an RNA chain thathas a function in the organism.
Living beings depend on genes, as theyspecify all proteins and functional RNAchains.
http://en.wikipedia.org/wiki/Heredityhttp://en.wikipedia.org/wiki/Organismhttp://en.wikipedia.org/wiki/DNAhttp://en.wikipedia.org/wiki/RNAhttp://en.wikipedia.org/wiki/Polypeptidehttp://en.wikipedia.org/wiki/RNAhttp://en.wikipedia.org/wiki/RNAhttp://en.wikipedia.org/wiki/Polypeptidehttp://en.wikipedia.org/wiki/RNAhttp://en.wikipedia.org/wiki/DNAhttp://en.wikipedia.org/wiki/Organismhttp://en.wikipedia.org/wiki/Heredity7/31/2019 Nucleotides Chemistry and Metabolism
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Gene expression Gene expression is the process by
which information from a gene is usedin the synthesis of a functionalgene product.
These products are often proteins, butin non-protein coding genes such asribosomal RNA (rRNA), transfer RNA (
tRNA) or small nuclear RNA (snRNA)genes, the product is a functional RNA.
http://en.wikipedia.org/wiki/Genehttp://en.wikipedia.org/wiki/Gene_producthttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/RRNAhttp://en.wikipedia.org/wiki/RRNAhttp://en.wikipedia.org/wiki/TRNAhttp://en.wikipedia.org/wiki/TRNAhttp://en.wikipedia.org/wiki/TRNAhttp://en.wikipedia.org/wiki/SnRNAhttp://en.wikipedia.org/wiki/SnRNAhttp://en.wikipedia.org/wiki/RNAhttp://en.wikipedia.org/wiki/RNAhttp://en.wikipedia.org/wiki/SnRNAhttp://en.wikipedia.org/wiki/SnRNAhttp://en.wikipedia.org/wiki/SnRNAhttp://en.wikipedia.org/wiki/TRNAhttp://en.wikipedia.org/wiki/TRNAhttp://en.wikipedia.org/wiki/TRNAhttp://en.wikipedia.org/wiki/RRNAhttp://en.wikipedia.org/wiki/RRNAhttp://en.wikipedia.org/wiki/RRNAhttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Gene_producthttp://en.wikipedia.org/wiki/Gene