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Purine and Pyrimidine
Biosynthesis
Course no. - MBB-591
Course Title - Master Seminar (0+1)
Presented By-
Sripati Abhiram Sahoo
I.D No- 120116215
Course Instructor-
Prof. Anil S. Kotasthane
2
Outline
Introduction
What are Purine and Pyrimidine bases
Molecular structure of Purine and pyrimidine bases
Nucleosides and Nucleotides
Synthesis of Purine nucleotides
Synthesis of Pyrimidine nucleotides
Flowchart of biosynthesis of nucleotides
3
Introduction
 Pyrimidine and purine are the names of the parent compounds of
two types of nitrogen-containing heterocyclic aromatic compounds.
N
N
Pyrimidine
N
N
N
N
H
Purine
4
Important Purines
 Adenine and guanine are the principal purines of both DNA and RNA.
 Caffeine (coffee) and theobromine (cocoa) are naturally occurring purines.
N
N
NH2
N
N
H
Adenine
O
HN
N
H
N
N
H2N
Guanine
5
Important Pyrimidines
 Pyrimidines that occur in DNA are cytosine and thymine. Cytosine and
uracil are the pyrimidines in RNA.
HN
N
H
O
O
Uracil
HN
N
H
O
O
CH3
Thymine
HN
N
H
NH2
O
Cytosine
6
Nucleosides and Nucleotides
Nucleoside is a structure formed by the combination of nitrogen base and sugar
where as Nucleotides are phosphoric acid esters of nucleosides.
N2 base Sugars Nucleoside
Adenine Deoxyribose/
Ribose
Adenosine
Guanine Deoxiribose/R
ibose
Guanosine
Thymine Deoxyribose Thymidine
Cytosine Deoxyribose/
Ribose
Cytidine
Uracil Ribose Uridine
Nucleos
ide
Phospho
ric acid
Nucleotides
Adenosine Phosphoric
acid
Adenylate
(AMP)
Guanosine Phosphoric
acid
Guanylate (
GMP)
Thymidine Phosphoric
acid
Thymidylate (
TMP)
Cytidine Phosphoric
acid
Cytidylate
(CMP)
Uridine Phosphoric
acid
Uridylate (UMP)
7
Synthesis of Purine Nucleotides
Synthesis
of purine
nucleotides
Denovo
synthesis
Site- Liver,
cytosol
Synthesis of
purine base step
by step on the
ribose 5-
phosphate
Salvage
pathway
Site - Plastid
Addition of ribose
5-phosphate to the
preformed purine
bases or addition
of phosphate to
the purine
nucleosides
8
Sources of Different Atoms of
Purine Ring
9
De novo Synthesis of Purine And
Pyrimidine
10
Purine Synthesis
 STEP-1
 STEP-2
11
 STEP-3 STEP-4
 STEP-5
 STEP-5
12
 STEP-6
 STEP-7
13
 STEP-8 STEP-9
14
 STEP-10 STEP-11
15
16
Salvage Pathway
It refers to the formation of purine nucleotides by the
1. Addition of ribose phosphate ( from PRPP) to the preformed purine
bases.
2. Addition of phosphate to the preformed purine nucleosides.
Significance
Salvage pathway provide a pathway for the utilization of purine bases
derived from diet (exogenous) and normal turnover of the nucleic
acids.
In erythrocytes, denovo syntheis of purine nucleotides does not occur
because of absence of PRPP amidotransferase. The requirement of
purine nucleotides is met by the salvage pathway.
17
Synthesis of Pyrimidine Nucleotides
Synthesis
of
pyrimidine
nucleotides
Denovo
synthesis
Site- liver, cytosol,
mitochondria
Synthesis of
pyrimidine
nucleotide refers to
the formation of
pyrimidine ring
structure followed
by the addition of
ribose phosphate.
Salvage
pathway
Site - Plastid
Formation of
pyrimidine
nucleotides from
pyrimidine bases
18
Sources of different atoms of pyrimidine
ring
19
2 ATP + HCO3
-
+ Glutamine + H2O
CO
O PO3
-2
NH2
Carbamoyl Phosphate
NH2
C
N
H
CH
CH2
C
COO
O
HO
O
Carbamoyl Aspartate
HN
C
N
H
CH
CH2
C
COO
O
O
Dihydroorotate
HN
C
N
H
C
CH
C
COO
O
O
Orotate
HN
C
N
C
CH
C
COO
O
O
HH
CH2
OH OH
H H
O
O2-
O3P

Orotidine-5'-monophosphate
(OMP)
HN
C
N
CH
CH
C
O
O
HH
CH2
OH OH
H H
O
O2-
O3P

Uridine Monophosphate
(UMP)
2 ADP +
Glutamate +
Pi
Carbamoyl
Phosphate
Synthetase II
Aspartate
Transcarbamoylase
(ATCase)
Aspartate
Pi
H2O
Dihydroorotase
Quinone
Reduced
Quinone
Dihydroorotate
Dehydrogenase
PRPP PPi
Orotate Phosphoribosyl
Transferase
CO2
OMP
Decarboxylase
Pyrimidine Synthesis
20
21
22
Salvage pathway 23
Summary
24
25

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Purine and Pyrimidine biosynthesis

  • 2. Purine and Pyrimidine Biosynthesis Course no. - MBB-591 Course Title - Master Seminar (0+1) Presented By- Sripati Abhiram Sahoo I.D No- 120116215 Course Instructor- Prof. Anil S. Kotasthane 2
  • 3. Outline Introduction What are Purine and Pyrimidine bases Molecular structure of Purine and pyrimidine bases Nucleosides and Nucleotides Synthesis of Purine nucleotides Synthesis of Pyrimidine nucleotides Flowchart of biosynthesis of nucleotides 3
  • 4. Introduction  Pyrimidine and purine are the names of the parent compounds of two types of nitrogen-containing heterocyclic aromatic compounds. N N Pyrimidine N N N N H Purine 4
  • 5. Important Purines  Adenine and guanine are the principal purines of both DNA and RNA.  Caffeine (coffee) and theobromine (cocoa) are naturally occurring purines. N N NH2 N N H Adenine O HN N H N N H2N Guanine 5
  • 6. Important Pyrimidines  Pyrimidines that occur in DNA are cytosine and thymine. Cytosine and uracil are the pyrimidines in RNA. HN N H O O Uracil HN N H O O CH3 Thymine HN N H NH2 O Cytosine 6
  • 7. Nucleosides and Nucleotides Nucleoside is a structure formed by the combination of nitrogen base and sugar where as Nucleotides are phosphoric acid esters of nucleosides. N2 base Sugars Nucleoside Adenine Deoxyribose/ Ribose Adenosine Guanine Deoxiribose/R ibose Guanosine Thymine Deoxyribose Thymidine Cytosine Deoxyribose/ Ribose Cytidine Uracil Ribose Uridine Nucleos ide Phospho ric acid Nucleotides Adenosine Phosphoric acid Adenylate (AMP) Guanosine Phosphoric acid Guanylate ( GMP) Thymidine Phosphoric acid Thymidylate ( TMP) Cytidine Phosphoric acid Cytidylate (CMP) Uridine Phosphoric acid Uridylate (UMP) 7
  • 8. Synthesis of Purine Nucleotides Synthesis of purine nucleotides Denovo synthesis Site- Liver, cytosol Synthesis of purine base step by step on the ribose 5- phosphate Salvage pathway Site - Plastid Addition of ribose 5-phosphate to the preformed purine bases or addition of phosphate to the purine nucleosides 8
  • 9. Sources of Different Atoms of Purine Ring 9
  • 10. De novo Synthesis of Purine And Pyrimidine 10
  • 12.  STEP-3 STEP-4  STEP-5  STEP-5 12
  • 16. 16
  • 17. Salvage Pathway It refers to the formation of purine nucleotides by the 1. Addition of ribose phosphate ( from PRPP) to the preformed purine bases. 2. Addition of phosphate to the preformed purine nucleosides. Significance Salvage pathway provide a pathway for the utilization of purine bases derived from diet (exogenous) and normal turnover of the nucleic acids. In erythrocytes, denovo syntheis of purine nucleotides does not occur because of absence of PRPP amidotransferase. The requirement of purine nucleotides is met by the salvage pathway. 17
  • 18. Synthesis of Pyrimidine Nucleotides Synthesis of pyrimidine nucleotides Denovo synthesis Site- liver, cytosol, mitochondria Synthesis of pyrimidine nucleotide refers to the formation of pyrimidine ring structure followed by the addition of ribose phosphate. Salvage pathway Site - Plastid Formation of pyrimidine nucleotides from pyrimidine bases 18
  • 19. Sources of different atoms of pyrimidine ring 19
  • 20. 2 ATP + HCO3 - + Glutamine + H2O CO O PO3 -2 NH2 Carbamoyl Phosphate NH2 C N H CH CH2 C COO O HO O Carbamoyl Aspartate HN C N H CH CH2 C COO O O Dihydroorotate HN C N H C CH C COO O O Orotate HN C N C CH C COO O O HH CH2 OH OH H H O O2- O3P  Orotidine-5'-monophosphate (OMP) HN C N CH CH C O O HH CH2 OH OH H H O O2- O3P  Uridine Monophosphate (UMP) 2 ADP + Glutamate + Pi Carbamoyl Phosphate Synthetase II Aspartate Transcarbamoylase (ATCase) Aspartate Pi H2O Dihydroorotase Quinone Reduced Quinone Dihydroorotate Dehydrogenase PRPP PPi Orotate Phosphoribosyl Transferase CO2 OMP Decarboxylase Pyrimidine Synthesis 20
  • 21. 21
  • 22. 22
  • 25. 25