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By
N.Santhosh Kumar
Asst.Professor
Department of Biochemistry
SIMS & RH
 Genetic protein is a conjugated protein & also known as Nucleo
proteins.
 Chromatin is largely composed of nucleoproteins
 It is composed on
Protein part: Histone (or) Protamines
Prostatic group [Non protein part]: Nucleic acids
 These compounds are involved in –
Cell- division
Transmission of hereditary factors
Protein Part Of Nucleoproteins
• The Histones are closely related basic proteins.
• They are 5 types – H1, H2A, H2B, H3 & H4.
• H1 Histones are tightly bound to chromatin & easily removed with a salt
solution after the chromatin become soluble.
• H2A, H2B , H3 & H4 are known as core proteins forming the
nucleosome.
• H2A – covalent linkages only
• H3 & H4 forms a tetramer
• H2A & H2 B form a dimers
• These tetramer & dimers are forms octamers.
• H1 are not necessary for reconstitution of the nucleosome core.
• But tetramer itself can confer nucleosomes.
H2A & H2B – rich in lysine
H3 & H4 – rich in arginine
PROTAMINES
Protamines are small, arginine-rich, nuclear proteins.
That replace Histones late in the haploid phase of spermatogenesis.
It is essential for sperm head condensation and DNA stabilization.
Non Protein Part of Nucleoproteins
Nucleic acids
9
Two Types:  DNA (Deoxy Ribonucleic Acid)
 RNA (Ribonucleic Acid)
Polymers of nucleotides (polynucleotides) held by 3' and 5'
phosphate bridges.
Made up of monomeric units – nucleotides
10
COMPOSITION OF NUCLEOTIDES
Nucleotide: Nitrogenous Base + Sugar + Phosphate
11
NITROGENOUS BASES
The nitrogenous bases found in nucleotides are aromatic
heterocyclic compounds.
Two types:
 Purine
 Pyrimidine
Purines are numbered in
the anti-clockwise
direction
It consists of a
pyrimidine ring &
imidazole ring fused
together.
Pyrimidines are numbered in
clockwise direction.
DNA contain - C &T
RNA contain - C &U
 Xanthine, Hypoxanthine are the intermediate products in purine
degradation .
 End product of purine degradation – Uric acid
( These are present in free state in cell.)
Plants contain methylated purines
Caffeine (1,3,7-tri methyl xanthine);
 It is present in coffee leaves.
In humans:
 Caffeine acts as a CNS stimulant,
Restoring alertness,
Temporarily warding off drowsiness
 It produces increased wakefulness, faster & better body
coordination.
 Increased motor sensitivity.
Depression of vagus thus leads to
Trechecardia ( Heart rate ).
It stimulates the Respiratory Center
sed The force & Depth of respiration.
Excess intake of caffeine cause.
Theophylline (1,3-Di methyl Xanthine);
• It is naturally found in TEA.
• Relaxing bronchial smooth muscle.
• Increasing heart rate, blood pressure & renal blood flow.
• Central nervous system stimulatory effect mainly on the
medullary respiratory center.
• Inhibits tubular reabsorption of Na  & Cl 
THEOBROMINE(3,7-Di methyl xanthine);
• It is also known as xantheose.
• It is found in leaves of the tea plants,
cola nut & chocolate
• It is used as a vasodilator (a blood vessel widener).
• It reduces blood pressure .
• Increases heart beat [CVS stimulant] & urine production.
METHYLATED PURINE BASES
Adenine Bases: 6-methyl adenine
7-methyl adenine
N6 methyl adenine
N6,N6 -Di methyl adenine
Guanine Bases: 2-methyl guanine
7-methyl guanine
N2-methyl guanine
N2,N2-Di methyl guanine
 Mono- & Di -N- methylated adenine & guanine
(mammalian messenger RNAs)
METHYLATED PYRIMIDINE BASES
Cytosine Bases
3-Methyl cytosine (bacterial & human DNA)
5-Methyl cytosine (mammalian genome)
5-hydroxy methyl cytosine (bacteriophages and viral
nucleic acids)
Uracil Bases
1-methyl uracil
3-methyl uracil
5- hydroxy methyl uracil
 The 5c Monosaccharides (Aldo-pentose) are found in the nucleic
acid structure.
RNA -- D-Ribose.
DNA -- D-deoxyribose.
 Two sugars are differ in structure at C2. Deoxy ribose has one
oxygen less at C2 compound to ribose.
The sugar is linked to the heterocyclic base via a -N- glycosidic bond,
almost always to
N-9 of a Purine . N-1 of a Pyrimidine
Nucleoside
(Base + Ribose sugar )
• The names of purine nucleosides end in -osine and the names of
pyrimidine nucleosides end in -idine.
Nitrogenous base Ribonucleoside Deoxy ribonucleoside
Adenine Adenosine (A) Deoxyadenosine (dA)
Guanine Guanosine (G) Deoxy guanosine (dG)
Thymine ----- Thymidine (dT)
Uracil Uridine (U) -----
Cytosine Cytidine (C) De oxy cytidine (dC)
Nucleotide
(Nucleoside + Phosphate )
• Nucleosides with a phosphoryl group esterified to a hydroxyl
group of the sugar to form mononucleotides
• The 3′- and 5′-nucleotides are nucleosides with a phosphoryl
group on the 3′- or 5′-hydroxyl group of the sugar,
respectively.
EXAMPLE: Adenosine Tri phosphate (ATP)
DNA
dAMP Deoxyadenosine monophosphate
dGMP Deoxyguanosine monophosphate
dCMP Deoxycytidine monophosphate
dTMP Deoxy thymidine monophosphate
RNA
AMP Adenosine monophosphate
GMP Guanosine monophosphate
CMP Cytidine monophosphate
UMP Uridine monophosphate 27
Classification:
 Adenosine nucleotides – ATP, ADP, AMP & c AMP
 Guanosine nucleotides – GTP, GDP, GMP & c GMP
 Uridine nucleotides - UTP, UDP, UMP & UDP- Glucose
 Cytidine nucleotides - CTP,CDP, CMP & Deoxy CDP
(derivatives of glucose ,choline)
 Miscellaneous - PAPS (active sulphate)
ADENOSINE NUCLEOTIDES
AMP
 First naturally occurring mono nucleotide.
 It is also formed from IMP through adenylosuccinate.
 It’s activates the enzyme PhosphoFructokinase.
Inhibited by ATP
 It is produced by degradation of 3’-5’ cyclic AMP by the enzyme
Phospho diesterase.
ADP
 Imp role as primary Po4 acceptor in
Oxidative Phosphorylation.
Photo Phosphorylation.
 It’s effect on control of Cellular Respiration.
Muscle Contraction .
 Activator of the enzyme glutamate dehydrogenase.
 It’s inhibits – fructose 1,6-bis-phosphatase
Adenylosuccinate synthetase.
ATP:
 Storage battery of the tissues.
 Required in the synthesis of
Phosphocreatine from Creatine
Fatty acids from Acetyl Co A.
Peptides & Proteins from a.a’s.
Formation of glucose from pyruvic acid.
Formation of active methionine.
 Imp source of energy for Muscle Contraction.
Transmission of Nerve impulses.
Transport of Nutrients.
Motility of Spermatozoa.
 Many synthetic reactions require energy
eg: Argino succinate synthetase reaction(urea cycle).
 The oxidation of Succinyl CoA in the TCA cycle involve
phosphorylation of GDP to form GTP.
 GTP- stimulation of adenylate cyclase enzyme
(formation cyclic AMP).
Required in Rhodopsin cycle
 Purine Synthesis (formation of AMP from IMP),
 Protein Synthesis.
UMP
 It is formed by the decarboxylation of Orotidine-5 P (biosynthesis of
pyrimidine nucleotide).
 UMP is convert to UDP & UTP by the enzyme nucleoside
diphoshokinase (presence of ATP).
UTP
 UTP involved in the Formation of CTP presence of CTP synthetase
& ATP.
 It reacts with glu-1-P to form UDP-Glu in the presence of the
enzyme UDPG pyrophosphorylase.
 UDPG required for the inter conversion of glucose & galactose in
the liver.
UDP
 UDP-Glucuronic acid involved in Conjugation reactions,
Detoxification of bilirubin & Drugs.
 Involved in biosynthesis of hyaluronic acid &heparin
 CDP-choline, CDP-glycine, CDP-ethanolamine are involved in the
formation of phospholipids.
 CMP-acetyl Neuraminic acid is imp precursor of Cell-wall of
polysaccharide in bacteria.
PAPS( Phospho Adenosine Phospho Sulphate):
 It is formed from ATP & So4 in liver.
 Required for
Bio.syn of heparin
Bio.syn of Chondroitin So4-( A,B,C & D)
Synthesis of Keratan sulphate
Formation of Sulfolipids
 Conjugation of phenols, indole, ethereal So4
41
Overall Functions of nucleotides
 Building blocks or monomeric units of nucleic acid (DNA and
RNA).
 Involved in the energy reactions of cell e.g. ATP.
 Control metabolic reactions as Allosteric regulators.
 Cyclic AMP and Cyclic GMP act as second messengers.
 Carries of high energy intermediates
 UDP glucose  Carbohydrates
 CDP acylglycerol  Lipids
 S -adenosylmethionine  Proteins.
Vitamin Coenzyme Function
Thiamine(vit-B1) TPP
(Thiamine Pyrophosphate)
Oxidative decarboxylation &
transketolase reaction
Riboflavin (Vit B2) FAD & FMN Oxidation & reduction reaction
NIACIN (Vit B3) NAD+ & NADP+ oxidoreduction reaction
Pantothenic acid (vit B5) Coenzyme A Acyl carrier
Cyno cobalamine
(Vit-B12)
Metylcobalamine &
Deoxyadenosylcobalamine
Transfer of CH3 group &
isomerisation reactions
Pyridoxine (Vit B6) PLP
Transamination , Deamination ,
Decarboxylation reactions of amino
acids.
Components of several coenzymes of B-complex vitamins
43
SYNTHETIC NUCLEOTIDE ANALOGS
(OR)
ANTI -METABOLITES
 Chemically Synthesized analogues of purines, Pyrimidines, their
nucleosides, and their nucleotides have therapeutic applications in
clinical medicine.
 It is prepared either by altering the heterocyclic ring or sugar moiety.
 It Inhibit the enzymes essential for nucleic acid synthesis.
 These are used chemotherapeutically to control cancer or infections.
Allopurinol
Purine analog
Treatment of Hyperuricemia
and Gout
5-fluorouracil or 5-Iodo Deoxy Uridine
 Used in treatment of cancer.
 It disrupts the normal replication process by interfering with the
correct formation of Watson- crick base pairing.
48
8-azaguanine,
3-deoxyuridine treatment of cancers
5- or 6-azauridine
5-or 6-azacytidine
They get incorporated into DNA and blocks the cell proliferation.
CYTARABINE
Chemotherapy of cancer & viral infection.
AZATHIOPURINE:
Immuno-Suppressive Agent (ISA).
It is used during organ transplantation.
AZIDOTHYMIDINE (AZT)
Structural analogue of Thymidine. used in the treatment of AIDS .
It terminates DNA synthesis catalyzed by the reverse transcriptase of
retroviruses such as HIV.
5-Iododeoxyuridine
 It is a nucleoside analogue has antiviral activity.
 It is used in the treatment of herpetic keratitis (Infection of the
cornea by harpers virus).
Arabinosyl cytosine
Cancer therapy as it interferes with DNA replication.
Arabinosyl adenine
Treatment of neurological disease, viral encephalitis.
Next PPT on
NA-02: Deoxyribonucleic Acid & Its
Functions
Any change, any loss, does
not makes us victims.
Others can shake you,
surprise you or disappoints
you.
But they can’t prevent you
from moving on.
Thank Q

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NA- 01: Chemistry of Nucleotides & It's clinical importance

  • 2.  Genetic protein is a conjugated protein & also known as Nucleo proteins.  Chromatin is largely composed of nucleoproteins  It is composed on Protein part: Histone (or) Protamines Prostatic group [Non protein part]: Nucleic acids
  • 3.  These compounds are involved in – Cell- division Transmission of hereditary factors
  • 4. Protein Part Of Nucleoproteins
  • 5. • The Histones are closely related basic proteins. • They are 5 types – H1, H2A, H2B, H3 & H4. • H1 Histones are tightly bound to chromatin & easily removed with a salt solution after the chromatin become soluble. • H2A, H2B , H3 & H4 are known as core proteins forming the nucleosome. • H2A – covalent linkages only • H3 & H4 forms a tetramer
  • 6. • H2A & H2 B form a dimers • These tetramer & dimers are forms octamers. • H1 are not necessary for reconstitution of the nucleosome core. • But tetramer itself can confer nucleosomes. H2A & H2B – rich in lysine H3 & H4 – rich in arginine
  • 7. PROTAMINES Protamines are small, arginine-rich, nuclear proteins. That replace Histones late in the haploid phase of spermatogenesis. It is essential for sperm head condensation and DNA stabilization.
  • 8. Non Protein Part of Nucleoproteins Nucleic acids
  • 9. 9 Two Types:  DNA (Deoxy Ribonucleic Acid)  RNA (Ribonucleic Acid) Polymers of nucleotides (polynucleotides) held by 3' and 5' phosphate bridges. Made up of monomeric units – nucleotides
  • 10. 10 COMPOSITION OF NUCLEOTIDES Nucleotide: Nitrogenous Base + Sugar + Phosphate
  • 11. 11 NITROGENOUS BASES The nitrogenous bases found in nucleotides are aromatic heterocyclic compounds. Two types:  Purine  Pyrimidine
  • 12. Purines are numbered in the anti-clockwise direction It consists of a pyrimidine ring & imidazole ring fused together.
  • 13. Pyrimidines are numbered in clockwise direction. DNA contain - C &T RNA contain - C &U
  • 14.  Xanthine, Hypoxanthine are the intermediate products in purine degradation .  End product of purine degradation – Uric acid ( These are present in free state in cell.)
  • 15. Plants contain methylated purines Caffeine (1,3,7-tri methyl xanthine);  It is present in coffee leaves. In humans:  Caffeine acts as a CNS stimulant, Restoring alertness, Temporarily warding off drowsiness  It produces increased wakefulness, faster & better body coordination.  Increased motor sensitivity.
  • 16. Depression of vagus thus leads to Trechecardia ( Heart rate ). It stimulates the Respiratory Center sed The force & Depth of respiration. Excess intake of caffeine cause.
  • 17. Theophylline (1,3-Di methyl Xanthine); • It is naturally found in TEA. • Relaxing bronchial smooth muscle. • Increasing heart rate, blood pressure & renal blood flow. • Central nervous system stimulatory effect mainly on the medullary respiratory center. • Inhibits tubular reabsorption of Na  & Cl 
  • 18. THEOBROMINE(3,7-Di methyl xanthine); • It is also known as xantheose. • It is found in leaves of the tea plants, cola nut & chocolate • It is used as a vasodilator (a blood vessel widener). • It reduces blood pressure . • Increases heart beat [CVS stimulant] & urine production.
  • 19. METHYLATED PURINE BASES Adenine Bases: 6-methyl adenine 7-methyl adenine N6 methyl adenine N6,N6 -Di methyl adenine Guanine Bases: 2-methyl guanine 7-methyl guanine N2-methyl guanine N2,N2-Di methyl guanine  Mono- & Di -N- methylated adenine & guanine (mammalian messenger RNAs)
  • 20. METHYLATED PYRIMIDINE BASES Cytosine Bases 3-Methyl cytosine (bacterial & human DNA) 5-Methyl cytosine (mammalian genome) 5-hydroxy methyl cytosine (bacteriophages and viral nucleic acids) Uracil Bases 1-methyl uracil 3-methyl uracil 5- hydroxy methyl uracil
  • 21.  The 5c Monosaccharides (Aldo-pentose) are found in the nucleic acid structure. RNA -- D-Ribose. DNA -- D-deoxyribose.  Two sugars are differ in structure at C2. Deoxy ribose has one oxygen less at C2 compound to ribose.
  • 22. The sugar is linked to the heterocyclic base via a -N- glycosidic bond, almost always to N-9 of a Purine . N-1 of a Pyrimidine Nucleoside (Base + Ribose sugar )
  • 23. • The names of purine nucleosides end in -osine and the names of pyrimidine nucleosides end in -idine. Nitrogenous base Ribonucleoside Deoxy ribonucleoside Adenine Adenosine (A) Deoxyadenosine (dA) Guanine Guanosine (G) Deoxy guanosine (dG) Thymine ----- Thymidine (dT) Uracil Uridine (U) ----- Cytosine Cytidine (C) De oxy cytidine (dC)
  • 24. Nucleotide (Nucleoside + Phosphate ) • Nucleosides with a phosphoryl group esterified to a hydroxyl group of the sugar to form mononucleotides • The 3′- and 5′-nucleotides are nucleosides with a phosphoryl group on the 3′- or 5′-hydroxyl group of the sugar, respectively.
  • 25.
  • 26. EXAMPLE: Adenosine Tri phosphate (ATP)
  • 27. DNA dAMP Deoxyadenosine monophosphate dGMP Deoxyguanosine monophosphate dCMP Deoxycytidine monophosphate dTMP Deoxy thymidine monophosphate RNA AMP Adenosine monophosphate GMP Guanosine monophosphate CMP Cytidine monophosphate UMP Uridine monophosphate 27
  • 28. Classification:  Adenosine nucleotides – ATP, ADP, AMP & c AMP  Guanosine nucleotides – GTP, GDP, GMP & c GMP  Uridine nucleotides - UTP, UDP, UMP & UDP- Glucose  Cytidine nucleotides - CTP,CDP, CMP & Deoxy CDP (derivatives of glucose ,choline)  Miscellaneous - PAPS (active sulphate)
  • 29. ADENOSINE NUCLEOTIDES AMP  First naturally occurring mono nucleotide.  It is also formed from IMP through adenylosuccinate.  It’s activates the enzyme PhosphoFructokinase. Inhibited by ATP  It is produced by degradation of 3’-5’ cyclic AMP by the enzyme Phospho diesterase.
  • 30. ADP  Imp role as primary Po4 acceptor in Oxidative Phosphorylation. Photo Phosphorylation.  It’s effect on control of Cellular Respiration. Muscle Contraction .  Activator of the enzyme glutamate dehydrogenase.  It’s inhibits – fructose 1,6-bis-phosphatase Adenylosuccinate synthetase.
  • 31. ATP:  Storage battery of the tissues.  Required in the synthesis of Phosphocreatine from Creatine Fatty acids from Acetyl Co A. Peptides & Proteins from a.a’s. Formation of glucose from pyruvic acid. Formation of active methionine.
  • 32.  Imp source of energy for Muscle Contraction. Transmission of Nerve impulses. Transport of Nutrients. Motility of Spermatozoa.  Many synthetic reactions require energy eg: Argino succinate synthetase reaction(urea cycle).
  • 33.
  • 34.  The oxidation of Succinyl CoA in the TCA cycle involve phosphorylation of GDP to form GTP.  GTP- stimulation of adenylate cyclase enzyme (formation cyclic AMP). Required in Rhodopsin cycle  Purine Synthesis (formation of AMP from IMP),  Protein Synthesis.
  • 35.
  • 36. UMP  It is formed by the decarboxylation of Orotidine-5 P (biosynthesis of pyrimidine nucleotide).  UMP is convert to UDP & UTP by the enzyme nucleoside diphoshokinase (presence of ATP).
  • 37. UTP  UTP involved in the Formation of CTP presence of CTP synthetase & ATP.  It reacts with glu-1-P to form UDP-Glu in the presence of the enzyme UDPG pyrophosphorylase.  UDPG required for the inter conversion of glucose & galactose in the liver.
  • 38. UDP  UDP-Glucuronic acid involved in Conjugation reactions, Detoxification of bilirubin & Drugs.  Involved in biosynthesis of hyaluronic acid &heparin
  • 39.  CDP-choline, CDP-glycine, CDP-ethanolamine are involved in the formation of phospholipids.  CMP-acetyl Neuraminic acid is imp precursor of Cell-wall of polysaccharide in bacteria.
  • 40. PAPS( Phospho Adenosine Phospho Sulphate):  It is formed from ATP & So4 in liver.  Required for Bio.syn of heparin Bio.syn of Chondroitin So4-( A,B,C & D) Synthesis of Keratan sulphate Formation of Sulfolipids  Conjugation of phenols, indole, ethereal So4
  • 41. 41 Overall Functions of nucleotides  Building blocks or monomeric units of nucleic acid (DNA and RNA).  Involved in the energy reactions of cell e.g. ATP.  Control metabolic reactions as Allosteric regulators.  Cyclic AMP and Cyclic GMP act as second messengers.  Carries of high energy intermediates  UDP glucose  Carbohydrates  CDP acylglycerol  Lipids  S -adenosylmethionine  Proteins.
  • 42. Vitamin Coenzyme Function Thiamine(vit-B1) TPP (Thiamine Pyrophosphate) Oxidative decarboxylation & transketolase reaction Riboflavin (Vit B2) FAD & FMN Oxidation & reduction reaction NIACIN (Vit B3) NAD+ & NADP+ oxidoreduction reaction Pantothenic acid (vit B5) Coenzyme A Acyl carrier Cyno cobalamine (Vit-B12) Metylcobalamine & Deoxyadenosylcobalamine Transfer of CH3 group & isomerisation reactions Pyridoxine (Vit B6) PLP Transamination , Deamination , Decarboxylation reactions of amino acids. Components of several coenzymes of B-complex vitamins
  • 44.  Chemically Synthesized analogues of purines, Pyrimidines, their nucleosides, and their nucleotides have therapeutic applications in clinical medicine.  It is prepared either by altering the heterocyclic ring or sugar moiety.  It Inhibit the enzymes essential for nucleic acid synthesis.  These are used chemotherapeutically to control cancer or infections.
  • 45. Allopurinol Purine analog Treatment of Hyperuricemia and Gout
  • 46.
  • 47. 5-fluorouracil or 5-Iodo Deoxy Uridine  Used in treatment of cancer.  It disrupts the normal replication process by interfering with the correct formation of Watson- crick base pairing.
  • 48. 48 8-azaguanine, 3-deoxyuridine treatment of cancers 5- or 6-azauridine 5-or 6-azacytidine They get incorporated into DNA and blocks the cell proliferation.
  • 49. CYTARABINE Chemotherapy of cancer & viral infection. AZATHIOPURINE: Immuno-Suppressive Agent (ISA). It is used during organ transplantation. AZIDOTHYMIDINE (AZT) Structural analogue of Thymidine. used in the treatment of AIDS . It terminates DNA synthesis catalyzed by the reverse transcriptase of retroviruses such as HIV.
  • 50. 5-Iododeoxyuridine  It is a nucleoside analogue has antiviral activity.  It is used in the treatment of herpetic keratitis (Infection of the cornea by harpers virus). Arabinosyl cytosine Cancer therapy as it interferes with DNA replication. Arabinosyl adenine Treatment of neurological disease, viral encephalitis.
  • 51. Next PPT on NA-02: Deoxyribonucleic Acid & Its Functions
  • 52. Any change, any loss, does not makes us victims. Others can shake you, surprise you or disappoints you. But they can’t prevent you from moving on. Thank Q