nucleotides chemistry and metabolism

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/RNA


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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
http://en.wikipedia.org/wiki/Thymidine_monophosphate


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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/Nucleotidase


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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/DNA


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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/Chromatin


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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/Heredity


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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

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