Synthesis of pyrimidines and purines

1. Synthesis of Pyrimidines
and Purines

2. Nucleotides: ---- Nitrogenous Base
---- Pentose Monosachharides
---- One/Two or Three Phosphate
Groups
Nitrogeneous Bases PURINES
PYRIMIDINES

3. Purine and Pyrimidine Structure
 Both DNA and RNA contain the same Purine bases :
Adenine (A) and Guanine (G)
 Both DNA and RNA contain the same Pyrimidine
structure cytosine (C), differ in their second Thymidine
base : DNA contains Thymine (T)
RNA contains Uracil (U)
Nucleosides:
Addition of Pentose sugar to a base through a Glycosidic
bond produces a Nucleoside.
E.g: Ribonucleoside,Deoxyribonucleoside.

4. Functions
 Participate in metabolic functions as diverse as energy metabolism,
protein synthesis, regulation of enzyme activity, and signal
transduction.
 Linked to vitamins or vitamin derivatives, nucleotides form a
portion of many coenzymes.
 ATP and ADP are the principal players in the energy transductions
that accompany metabolic interconversions and oxidative
phosphorylation.
 Cyclic nucleotides cAMP and cGMP serve as the second messengers
in hormonally regulated events.
 Medical applications : Use of synthetic purine and pyrimidine
analogs that contain halogens, thiols, or additional nitrogen atoms
in the chemotherapy of cancer and AIDS, and as suppressors of the
immune response during organ transplantation.

6. Can Cells Synthesize Purine Nucleotides??
 Nearly all organisms synthesize purines and
pyrimidines “denovo biosynthesis Pathway“.
Many Organisms also “Salvage”purines from diet
and degradative pathways.

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How do Cells synthesize the Purine
Nucleotides??

8. Synthesis of Purine Nucleotides
 denovo Synthesis Total Ten Steps in synthesis
of Purine Nucleotide.
 Salvage Pathway

9. A. Synthesis of 5-Phosphoribosyl -1-
pyrophosphate

10. B. Synthesis of 5-Phosphoribosylamine
 Committed step in Purine Synthesis.

11. C. Synthesis of Inosine Monophosphate, the
“PARENT’ Purine Nucleotide
 Next Nine steps in Purine biosynthesis leads to
formation of Inosine Monophosphate(IMP).
 Four Steps require ATP as an energy source and two
steps in the pathway require N10-formyltetrahydrofolate
as a one carbon donor.

12. Synthesis of Adenosine and Guanosine
Monophosphate
 Two step Energy-requiring pathway.
 Synthesis of AMP requires GTP and Synthesis
of GMP requires ATP Cross Regulation

13.  If both AMP and GMP are present in adequate
amounts, the denovo pathway of purine synthesis is
TURNED OFF at the Amidotransferase step.

17. Synthetic Inhibitors of Purine Synthesis
 Sulfonamides
 Methotrexate
 Designed to inhibit the growth of rapidly dividing
microorganisms without interfering with human cell
functions.

18. How is Pyrimidine synthesized????
 In contrast to Purine ring, Pyrimidine ring is completed
before the addition of 5-ribose Phosphate.
 Carbamoyl Phosphate and Aspartate are the precursors
of the Six-membered Pyrimidine Ring.

19. A. Synthesis of Carbomyl Phosphate
 Glutamine + CO2 C
Carbomyl Phosphate Synthetase II
Regulated Step in this
pathway.
Carbomyl Phosphate

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CPS I CPS II
Cellular Location Mitochondria Cytosol
Pathway Involved Urea Cycle Pyrimidine Synthesis
Source of
Nitrogen
Ammonia Glutamine
Regulators Acivator: N-acetyl-
Glutamate
Activator :PRPP
Inhibitor : UTP
Comparison between CPS I and CPS II

21. B. Synthesis of Orotic Acid
 Second Step Formation of
CarbomylAspartate.

22. C. Formation of a Pyrimidine Nucleotide
 Orotidine Monophosphate(OMP)
Parent Pyrimidine mononucleotide formed from
Completed Pyrimidine ring.
 OMP Orotidylate Decarboxylase Uridine
Monophosphate
(UMP)
removes carboxylic group.
 Orotate Phosphoribosyltransferase and Orotidylate
Decarboxylase are also catalytic domains of a single
Polypeptide chain called UMP Synthase.

23. Orotic Aciduria
 Deficiency of one or both activities of
the Bifunctional Enzyme
Orotic Acid in Urine.
 UMP thus formed is converted to UDP and
UTP.

24. D. Synthesis of Cytidine Triphosphate
UTP Amination Cytidine
Triphosphate
(CTP)

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E. Synthesis of Deoxythymidine
Monophosphate
dUMP Thymidylate synthase dTMP

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Q. The rate of DNA synthesis in a culture of cells could
be most accurately determined by measuring the
incorporation of which of the following radiolabeled
compounds?
A. Adenine.
B. Guanine.
C. Phosphate.
D. Thymidine.

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Q. A 1-year-old female patient is lethargic, weak, and
anemic. Her height and weight are both low for her
age. Her urine contains an elevated level of orotic
acid. The administration of which of the following
compounds is most likely to relieveher symptoms?
A. Adenine.
B. Guanine.
C. Hypoxanthine.
D. Thymidine.
E. Uridine.

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