Nucleotides & minor bases

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Nucleoproteins
M.Prasad Naidu MSc Medical Biochemistry, Ph.D,.
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Nucleoproteins are conjugated proteins (basic
proteins nucleic acids) Nucleic acids DNA
and RNA DNA is the chemical basis of
heredity. Sir diagram
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Nucleoside
and nucleotide Nucleic acids are polymers of
mononucleotides held by 3' and 5' phosphodiester
bonds Nucleoside --- Base
Sugar Nucleotide --- Base sugar
phosphate
(phosphorylated nucleoside ).
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BASES They are
nitrogenous heterocyclic compounds TWO Types
Purines
Pyrimidines . Adenine
.Cytosine .
Guanine
.Thymine
.Uracil Purines
are numbered in anticlockwise direction in
pyrimidine ring and clockwise direction in
imidazole ring. Pyrimidines are numbered in
clockwise direction
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NUMBERING OF PURINE AND PYRIMIDINE RINGS
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PURINE BASES
ADENINE - 6 amino purine GUANINE
2-amino 6 oxy purine
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6
2
9
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PYRIMIDINE BASES

• CYTOSINE (both DNA and RNA)
• 2-oxy 4 amino pyrimidine

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2
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• THYMINE (DNA)
• 2,4 - dioxy 5methylpyrimidine

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5
2
9

• URACIL (RNA)
• 2,4 -dioxypyrimidine

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2
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SUGARS D
- RIBOSE D 2- deoxy ribose
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Numerals with prime ( ' ) distinguish carbon
atoms of sugar from those of heterocycle
nitrogenous base. The sugar ( c1 ) is linked
to base via a beta N glycosidic bond , almost
always to N-1 of pyrimidine and N-9 of purine.
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• The hydroxyl groups of adenosine are esterified
  with
• phosphate to produce 3 ' or 5' monophophate.
• 5' OH is commonly esterified ,hence 5'
  omitted.
• Adenosine 5' monophosphate -------
  AMP(adenylate)
• Addition of 2nd or 3 rd phosphate to nucleoside
  results
• in nucleoside diphosphate and triphosphate
• respectively.

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• Base Sugar Nucleoside
• Adenine Ribose Adenosine
• Guanine Ribose Guanosine
• Cytosine Ribose Cytidine
• Uracil Ribose Uridine
• Adenine Deoxyribose Deoxy Adenosine
• Guanine Deoxyribose Deoxy Guanosine
• Cytosine Deoxyribose Deoxy Cytidine
• Thymine Deoxyribose Deoxy Thymidine

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Principal bases ,nucleosides and nucleotides
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• Nucleoside Phosphate Nucleotide
• Adenosine Phosphate Adenylate(AMP)
• Guanosine Phosphate Guanylate(GMP)
• Cytidine Phosphate
  Cytidylate(CMP)
• Uridine Phosphate Uridylate(UMP)

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deoxyNucleoside Phosphate
deoxyNucleotide Deoxyadenosine phosphate -
deoxyadenylate(dAMP) Deoxy guanosinephosphate -
deoxyguanylate(dGMP)
Deoxycytidine phosphate ---
deoxycytidylate(dCMP) Deoxythymidine phosphate -
deoxythymidylate(dTMP)
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• Minor/unusual bases
• Specific DNAs and RNAs of both prokaryotes and
  eukaryotes
• contain smaller amounts of additional bases
  termed minor or
• unusual bases.
• These bases are functionally important and hence
  not of minor Physiologic significance .
• They are widely distributed in nature.

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• Minor bases cont..
• 5-methylcytosine present in both bacterial and
• human DNA
• 2. Mono and di methylated adenine present in
• mammalian RNA.
• 3. Di methyl guanine present in mRNA.
• 4. Various derived bases in tRNA s.eg
  pseudouridine.
• 5- hydroxy methyl cytosine of bacteriophage DNA
  occur in
• bacteria and viral nucleic acids.

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• Functions of minor bases
• Small quantities of unusual bases form structural
  
• components of DNA and RNA.
• 2.They regulate the half life of RNAs
• 3. The presence of specific methylated nucleotide
• bases protect the human DNA from the DNAases
• arising from viral /bacterial pathogens.

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• Plants Methylated bases include xanthine
  derivatives
• Caffeine of coffee -- 1,3,7
  trimethyl xanthine
• Theobromine of cocoa -- 3,7 dimethyl
  xanthine
• Theophylline of tea -- 1, 7
  dimethyl xanthine

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• Classification of nucleotides
• Adenosine nucleotides eg ATP, ADP,AMP, cyclic
  AMP
• 2.Guanosine nucleotides eg GTP, GDP , GMP ,
• cyclic GMP
• 3.Cytidine nucleotides eg CTP,CDP,CMP
  ,CDP-choline
• 4.Uridine nucleotides egUTP,UDP,UMP ,UDP
  glucose

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• Functions of Nucleotides
• Building blocks of nucleic acids DNA , RNA.
• Involved in energy reactions of the cell eg
  ATP
• Form part of many coenzymes of B-complex
• vitamins like FAD,NAD,NADP

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• UDP-Glucose is involved in glycogen synthesis.
• UDP- glucuronic acid is involved in conjugation
  reactions eg bilirubin.
• CTP is required for synthesis of
  phosphoglycerides and sphingomyelin
• Regulatory nucleotides/second messengers eg
  Cyclic AMP , cyclic GMP.

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• ATP
• Adenosine triphosphate.
• Major biologic transducer of free energy.
• Intra cellular conc is 1 mmol/L.
• Most abundant free nucleotide in mammalian
  cells.

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• cAMP
• Cyclic adenosine 3,5- monophosphate.
• Formed from ATP, catalyzed by adenylyl cyclase.
• Second messenger.
• IC conc is 1 nmol/L.
• Its level is maintained by interaction of
  adenylyl cyclase
• cAMP phosphodiesterase.

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• Adenosine 3-phosphate -5-phospho sulfate (PAPS)
• Active sulfate
• Sulfate donor for formation of sulfated
  proteoglycans, urinary metabolism of drug
  excreted as sulfate conjugates.

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• Synthetic analogs of purine/ pyrimidine
  nucleotides
• Mechanism Of action
• Inhibition of specific enzymes essential for
  
• nucleic acid synthesis.
• Incorporation of metabolites of the drug into
  nucleic acids that affect base pairing ,
  essential for accurate transfer of information.

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• USES
• Chemotherapeutic agents for cancer ,AIDS and
  suppressors of immune rejection in organ
  transplantation.
• Eg
• 1. Allopurinol used in gout inhibits xanthine
  oxidase
• 2.Cytarabine used in cancer and viral
  infections.
• 3 . Azathiopurine used in organ transplantation
• 4. 5- iodo deoxy uridine used in herpetic
  keratitis

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