this is the information about biosynthesis of purines and pyrimidines how they are synthesized via various pathways

1. Biosynthesis of Purines and
Pyrimidines
NIDHI GOSSAI

2. Brief history
• 1869: isolated DNA from salmon sperm (Friedrich Miescher)
• 1944: proved DNA is genetic materials (Avery et al.)
• 1953: discovered DNA double helix (Watson and Crick)
• 1968: decoded the genetic codes (Nirenberg)
• 1981: invented DNA sequencing method (Gilbert and Sanger)
• 1987: launched the human genome project
• 2001: accomplished the draft map of human genome

3. Nucleic acid
Deoxyribonucleic acid, DNA
Ribonucleic acid, RNA

4. •DNA and RNA are polymers of nucleotide
units.
• DNA (RNA) consists of 4 kinds of
ribonucleotide units linked together through
covalent bonds.
• Each nucleotide unit is composed of
a nitrogenous base
a pentose sugar
a phosphate group
1. The components of DNA and RNA

41. Purine Catabolism and Salvage
• All purine degradation leads to uric acid (but it might not stop
there)
• Ingested nucleic acids are degraded to nucleotides by
pancreatic nucleases, and intestinal phosphodiesterases in
the intestine
• Group-specific nucleotidases and non-specific phosphatases
degrade nucleotides into nucleosides
– Direct absorption of nucleosides
– Further degradation
Nucleoside + H2O  base + ribose (nucleosidase)
Nucleoside + Pi  base + r-1-phosphate (n. phosphorylase)
NOTE: MOST INGESTED NUCLEIC ACIDS ARE DEGRADED AND EXCRETED.

42. Intracellular Purine Catabolism
• Nucleotides broken into nucleosides by action of 5’-
nucleotidase (hydrolysis reactions)
• Purine nucleoside phosphorylase (PNP)
– Inosine  Hypoxanthine
– Xanthosine  Xanthine
– Guanosine  Guanine
– Ribose-1-phosphate splits off
• Can be isomerized to ribose-5-phosphate
• Adenosine is deaminated to Inosine (ADA)

43. Intracellular Purine Catabolism
• Xanthine is the point of convergence for the
metabolism of the purine bases
• Xanthine  Uric acid
– Xanthine oxidase catalyzes two reactions
• Purine ribonucleotide degradation pathway is
same for purine deoxyribonucleotides

44. Adenosine Degradation

45. Xanthosine Degradation
• Ribose sugar gets recycled (Ribose-1-Phosphate  R-5-P )
– can be incorporated into PRPP (efficiency)
• Hypoxanthine is converted to Xanthine by Xanthine Oxidase
• Guanine is converted to Xanthine by Guanine Deaminase
• Xanthine gets converted to Uric Acid by Xanthine Oxidase

46. A CASE STUDY : GOUT
• A 45 YEAR OLD MAN AWOKE FROM SLEEP WITH A PAINFUL AND SWOLLEN
RIGHT GREAT TOE. ON THE PREVIOUS NIGHT HE HAD EATEN A MEAL OF
FRIED LIVER AND ONIONS, AFTER WHICH HE MET WITH HIS POKER GROUP
AND DRANK A NUMBER OF BEERS.
• HE SAW HIS DOCTOR THAT MORNING, “GOUTY ARTHRITIS” WAS
DIAGNOSED, AND SOME TESTS WERE ORDERED. HIS SERUM URIC ACID
LEVEL WAS ELEVATED AT 8.0 mg/dL (NL < 7.0 mg/dL).
• THE MAN RECALLED THAT HIS FATHER AND HIS GRANDFATHER, BOTH OF
WHOM WERE ALCOHOLICS, OFTEN COMPLAINED OF JOINT PAIN AND
SWELLING IN THEIR FEET.

47. A CASE STUDY : GOUT
• THE DOCTOR RECOMMENDED THAT THE MAN USE NSAIDS
FOR PAIN AND SWELLING, INCREASE HIS FLUID INTAKE (BUT
NOT WITH ALCOHOL) AND REST AND ELEVATE HIS FOOT. HE
ALSO PRESCRIBED ALLOPURINOL.
• A FEW DAYS LATER THE CONDITION HAD RESOLVED AND
ALLOPURINOL HAD BEEN STOPPED. A REPEAT URIC ACID
LEVEL WAS OBTAINED (7.1 mg/dL). THE DOCTOR GAVE THE
MAN SOME ADVICE REGARDING LIFE STYLE CHANGES.

48. Gout
• Impaired excretion or overproduction of uric
acid
• Uric acid crystals precipitate into joints (Gouty
Arthritis), kidneys, ureters (stones)
• Lead impairs uric acid excretion – lead
poisoning from pewter drinking goblets
– Fall of Roman Empire?
• Xanthine oxidase inhibitors inhibit production
of uric acid, and treat gout
• Allopurinol treatment – hypoxanthine analog
that binds to Xanthine Oxidase to decrease uric
acid production

49. ALLOPURINOL IS A XANTHINE OXIDASE INHIBITOR
A SUBSTRATE ANALOG IS CONVERTED TO AN INHIBITOR, IN THIS CASE
A “SUICIDE-INHIBITOR”

50. Degradation of Pyrimidines
• CMP and UMP degraded to bases similarly to
purines
– Dephosphorylation
– Deamination
– Glycosidic bond cleavage
• Uracil reduced in liver, forming b-alanine
– Converted to malonyl-CoA  fatty acid synthesis
for energy metabolism

51. Pyrimidine nucleotides are converted to nucleosides by nonspecific phosphatases.
Cytidine and deoxycytidine are deaminated to uridine and deoxyuridine, respectively, by
Pyridimine Nucleoside deaminase.
Uridine phophorylase catalyzes phosphorolysis of uridine, deoxyuridine, and
deoxythymidine to uracil and thymine.