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BIOSYNTHESIS OF PYRIMIDINE
PRESENTED BY :
GOWINYA S
INTRODUCTION
 Pyrimidines are essential components of DNA (cytosine, thymine) and RNA (cytosine,
uracil).
 They are needed for genetic information storage, energy transfer, and cellular
signaling.
 Pyrimidine synthesis starts by forming the pyrimidine ring structure before attaching it
to ribose-5-phosphate to create nucleotides.
 The process begins with glutamine, carbon dioxide (CO₂), and aspartate as starting
materials.
 Six enzyme-catalyzed steps convert these materials into uridine monophosphate
(UMP).
 UMP serves as a precursor for other pyrimidine nucleotides, such as cytidine
triphosphate (CTP) and thymidine triphosphate (TTP).
 UMP, CTP, and TTP are essential for DNA/RNA synthesis, cellular energy maintenance,
and metabolic regulation.
STRUCTURE
Pyrimidine Structure
Pyrimidine is a six-membered
heterocyclic aromatic ring composed
of four carbon atoms and two
nitrogen atoms at positions 1 and 3.
The structure resembles benzene but
is more chemically reactive due to the
nitrogen atoms, which influence its
properties. The molecular formula of
pyrimidine is , and it has a planar
structure, allowing it to engage in
stacking interactions.
Cytidine Triphosphate (CTP) Structure
Cytidine Triphosphate (CTP) is a
nucleotide composed of three main
components: a cytosine base, a ribose
sugar, and three phosphate groups.
Thymidine Triphosphate (TTP)
Structure
Thymidine Triphosphate (TTP),
also known as deoxythymidine
triphosphate (dTTP), is a
nucleotide with three major
components: a thymine base, a
deoxyribose sugar, and a
triphosphate group.
PYRIMIDINE SYNTHESIS PATHWAY
ENZYME USED
 Carbamoyl Phosphate Synthetase II (CPS II)
 Aspartate Transcarbamoylase (ATCase)
 Dihydroorotase
 Dihydroorotate Dehydrogenase
 Orotate Phosphoribosyltransferase
 Orotidine-5'-Phosphate Decarboxylase
STEP 1 : Formation of Carbamoyl Phosphate
The pathway starts with the formation of carbamoyl phosphate, which is synthesized from
glutamine, carbon dioxide (CO₂), and ATP by the enzyme carbamoyl phosphate
synthetase II (CPS II).
Glutamine CO2 2 ATP CARBAMOYL PHOSPHATE
STEP 2 : Formation of Carbamoyl Aspartate
Carbamoyl phosphate then reacts with aspartate, catalyzed by the enzyme
aspartate transcarbamoylase (ATCase), to form carbamoyl aspartate.
Carbamoyl
Phosphate
Aspartate CARBAMOYL ASPARTATE
STEP 3 : Formation of Dihydroorotate
Carbamoyl aspartate undergoes a ring closure reaction to form
dihydroorotate, catalyzed by dihydroorotase.
CARBAMOYL ASPARTATE DIHYDROOROTATE
STEP 4 : Oxidation to Orotate
Dihydroorotate is oxidized to orotate by the enzyme dihydroorotate
dehydrogenase, which is located on the inner mitochondrial membrane.
Dihydrootate OROTATE
STEP 5 : Formation of Orotidine Monophosphate (OMP)
Orotate then combines with phosphoribosyl pyrophosphate (PRPP) to form orotidine
monophosphate (OMP), a reaction catalyzed by orotate phosphoribosyltransferase.
Orotate PRPP
OROTIDINE-5’-
MONOPHOSPHATE
STEP 6 : Formation of Uridine Monophosphate (UMP)
Finally, OMP is decarboxylated by Orotidine-5'-Phosphate Decarboxylase
to form uridine monophosphate (UMP), the first major pyrimidine nucleotide.
Orotate OROTIDINE-5’-
MONOPHOSPHATE ( UMP )
CO2
IMPORTANCE
 Genetic Material Formation: Pyrimidines are key components of DNA and RNA. In DNA, they pair with purine
bases (adenine and guanine) to form stable genetic structures. For instance, cytosine pairs with guanine, and
thymine pairs with adenine in DNA (or uracil with adenine in RNA).
 Cell Growth and Division: Cells require a steady supply of pyrimidines to support DNA replication and repair. The
biosynthesis of pyrimidines, therefore, directly supports cell division, growth, and regeneration.
 Metabolic Regulation: Pyrimidine nucleotides are involved in energy metabolism and cellular signaling. For
example, uridine triphosphate (UTP) and cytidine triphosphate (CTP) participate in glycogen synthesis and
phospholipid biosynthesis, which are vital for energy storage and membrane structure.
 Anticancer and Antimicrobial Targets: Since rapidly dividing cells, such as cancer cells and pathogens, require
large amounts of nucleotides, inhibiting pyrimidine biosynthesis is a strategy in the development of anticancer
and antimicrobial drugs. Drugs that target enzymes in the pyrimidine synthesis pathway can limit cell proliferation
and pathogen survival.
 Mitochondrial Function: Pyrimidine biosynthesis is necessary for mitochondrial DNA maintenance and function,
which impacts cellular respiration and energy production.
CIRITICAL QUESTTON
1.Pyrimidine is Necessary for ?
2.The enzyme used in the conversation of Dihydroorotatae to Orotate?
3.What is the structural reaction undergoes to form dihydroorotate from
carbamoyl aspartate ?
4.The enzyme dihydroorotate dehydrogenase is located in ?
5.What is the byproduct of orotate ?
6.The Carbamoyl Phosphate is synthesized from ?
THANK YOU !!!

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Biosynthesis of Pyrimidine with steps.ppt

  • 2. INTRODUCTION  Pyrimidines are essential components of DNA (cytosine, thymine) and RNA (cytosine, uracil).  They are needed for genetic information storage, energy transfer, and cellular signaling.  Pyrimidine synthesis starts by forming the pyrimidine ring structure before attaching it to ribose-5-phosphate to create nucleotides.  The process begins with glutamine, carbon dioxide (CO₂), and aspartate as starting materials.  Six enzyme-catalyzed steps convert these materials into uridine monophosphate (UMP).  UMP serves as a precursor for other pyrimidine nucleotides, such as cytidine triphosphate (CTP) and thymidine triphosphate (TTP).  UMP, CTP, and TTP are essential for DNA/RNA synthesis, cellular energy maintenance, and metabolic regulation.
  • 3. STRUCTURE Pyrimidine Structure Pyrimidine is a six-membered heterocyclic aromatic ring composed of four carbon atoms and two nitrogen atoms at positions 1 and 3. The structure resembles benzene but is more chemically reactive due to the nitrogen atoms, which influence its properties. The molecular formula of pyrimidine is , and it has a planar structure, allowing it to engage in stacking interactions. Cytidine Triphosphate (CTP) Structure Cytidine Triphosphate (CTP) is a nucleotide composed of three main components: a cytosine base, a ribose sugar, and three phosphate groups. Thymidine Triphosphate (TTP) Structure Thymidine Triphosphate (TTP), also known as deoxythymidine triphosphate (dTTP), is a nucleotide with three major components: a thymine base, a deoxyribose sugar, and a triphosphate group.
  • 5. ENZYME USED  Carbamoyl Phosphate Synthetase II (CPS II)  Aspartate Transcarbamoylase (ATCase)  Dihydroorotase  Dihydroorotate Dehydrogenase  Orotate Phosphoribosyltransferase  Orotidine-5'-Phosphate Decarboxylase
  • 6. STEP 1 : Formation of Carbamoyl Phosphate The pathway starts with the formation of carbamoyl phosphate, which is synthesized from glutamine, carbon dioxide (CO₂), and ATP by the enzyme carbamoyl phosphate synthetase II (CPS II). Glutamine CO2 2 ATP CARBAMOYL PHOSPHATE
  • 7. STEP 2 : Formation of Carbamoyl Aspartate Carbamoyl phosphate then reacts with aspartate, catalyzed by the enzyme aspartate transcarbamoylase (ATCase), to form carbamoyl aspartate. Carbamoyl Phosphate Aspartate CARBAMOYL ASPARTATE
  • 8. STEP 3 : Formation of Dihydroorotate Carbamoyl aspartate undergoes a ring closure reaction to form dihydroorotate, catalyzed by dihydroorotase. CARBAMOYL ASPARTATE DIHYDROOROTATE
  • 9. STEP 4 : Oxidation to Orotate Dihydroorotate is oxidized to orotate by the enzyme dihydroorotate dehydrogenase, which is located on the inner mitochondrial membrane. Dihydrootate OROTATE
  • 10. STEP 5 : Formation of Orotidine Monophosphate (OMP) Orotate then combines with phosphoribosyl pyrophosphate (PRPP) to form orotidine monophosphate (OMP), a reaction catalyzed by orotate phosphoribosyltransferase. Orotate PRPP OROTIDINE-5’- MONOPHOSPHATE
  • 11. STEP 6 : Formation of Uridine Monophosphate (UMP) Finally, OMP is decarboxylated by Orotidine-5'-Phosphate Decarboxylase to form uridine monophosphate (UMP), the first major pyrimidine nucleotide. Orotate OROTIDINE-5’- MONOPHOSPHATE ( UMP ) CO2
  • 12. IMPORTANCE  Genetic Material Formation: Pyrimidines are key components of DNA and RNA. In DNA, they pair with purine bases (adenine and guanine) to form stable genetic structures. For instance, cytosine pairs with guanine, and thymine pairs with adenine in DNA (or uracil with adenine in RNA).  Cell Growth and Division: Cells require a steady supply of pyrimidines to support DNA replication and repair. The biosynthesis of pyrimidines, therefore, directly supports cell division, growth, and regeneration.  Metabolic Regulation: Pyrimidine nucleotides are involved in energy metabolism and cellular signaling. For example, uridine triphosphate (UTP) and cytidine triphosphate (CTP) participate in glycogen synthesis and phospholipid biosynthesis, which are vital for energy storage and membrane structure.  Anticancer and Antimicrobial Targets: Since rapidly dividing cells, such as cancer cells and pathogens, require large amounts of nucleotides, inhibiting pyrimidine biosynthesis is a strategy in the development of anticancer and antimicrobial drugs. Drugs that target enzymes in the pyrimidine synthesis pathway can limit cell proliferation and pathogen survival.  Mitochondrial Function: Pyrimidine biosynthesis is necessary for mitochondrial DNA maintenance and function, which impacts cellular respiration and energy production.
  • 13. CIRITICAL QUESTTON 1.Pyrimidine is Necessary for ? 2.The enzyme used in the conversation of Dihydroorotatae to Orotate? 3.What is the structural reaction undergoes to form dihydroorotate from carbamoyl aspartate ? 4.The enzyme dihydroorotate dehydrogenase is located in ? 5.What is the byproduct of orotate ? 6.The Carbamoyl Phosphate is synthesized from ?