Degradation of Nucleic acids Purine nucleotide Degradation Pyrimidine nucleotide Degradation

1. Degradation of Nucleic acids

2. Nucleic acids
DNA & RNA
NUCLEOTIDE
A nucleotide is the fundamental
building block of nucleic acid

4. Nucleotides are Two types
# RNA Nucleotides / ribonucleotides
# DNA Nucleotides/ Deoxyribonucleotides
These, in turn, are of two classes, namely
+ Purine nucleotides
+ Pyrimidine nucleotides

5. Ribonucleotides
+ Adenosine monophosphate ( AMP)
+ Guanosine monophosphate ( GMP)
+ Cytidine monophosphate ( CMP)
+ Uridine monophosphate (UMP)

6. Image credit: Shutter stock

7. Deoxyribonucleotides
+ Deoxyadenosine monophosphate(dAMP)
+ Deoxyguanosine monophosphate (dGMP)
+ Deoxycytidine monophosphate (dCMP)
+ Deoxythymidine monophosphate (dTMP)

8. Image credit: Shutter stock

9. # PURINE NUCLEOTIDES
+ AMP, GMP, d AMP, d GMP
# PYRIMIDINE NUCLEOTIDES
+ CMP, UMP, d CMP, d TMP

10. Nucleosides
+ Adenosine, Deoxyadenosine
+ Guanosine, Deoxyguanosine
+ Cytidine, Deoxycytidine
+ Uridine, Deoxythymidine

12. + Dietary nucleic acids survive the acidic
medium of the stomach, they are degraded
to their component nucleotides, mainly in
the intestine, by pancreatic nucleases &
Intestinal phosphodiesterases
+ Nucleotides are then hydrolyzed to
nucleosides

13. + Nucleosides maybe directly absorbed by
the intestinal mucosa or further degraded
to free bases and ribose or ribose-1-
phosphate

14. Nucleotide Degradation
1) Purine nucleotide Degradation
2) Pyrimidine nucleotide
Degradation

15. PURINE NUCLEOTIDE – DEGRADATION
+ Purine nucleotides are sequentially degraded by the
removal or alternation of portions of the nucleotide
+ The end product of purine catabolism in human is uric
acid.
+ Mammals other than primates oxidize uric acid further
to allantoin, which in some animals other than mammals,
may be converted to urea or even ammonia.

17. STEPS : ADENINE NUCLEOTIDE
Step No:1
Case1: An amino group is removed from AMP
to produce IMP
AMPD = AMP deaminase

18. Case 2
# Adenosine is produced from AMP
by the action of5’-NT
Nucleotidase is a hydrolytic enzyme that catalyzes the hydrolysis
of a nucleotide into a nucleoside

19. STEP 2
Adenosine ( In case 2 ) & IMP ( In
case 1) are converted into Inosine

21. STEP 3
Inosine is converted into Hypoxanthine

22. STEP 4
Hypoxanthine is oxidized to Xanthine
Xanthine oxidase (XO) is an important enzyme catalyzing the
hydroxylation of hypoxanthine to xanthine and xanthine to uric acid

23. Xanthine oxidase
A flavoenzyme with an atom of molybdenum and
four iron-sulfur centers in its prosthetic group.
Molecular oxygen is the electron acceptor in this
complex reaction.

24. STEP 5
Xanthine further oxidized to Uric acid
+ Uric acid is excreted through urine

25. STEPS : GUANINE NUCLEOTIDE
Step No:1
GMP is coverted into Guanosine
GMP
GUANOSINE

26. STEP 2
Guanosine is converted into Guanine

27. STEP 3
Guanine is deaminated to form Xanthine

28. STEP 4

30. # Uric acid is the excreted end product
of purine catabolism in primates, birds,
and some other animals. A healthy adult
human excretes uric acid at a rate of
about 0.6 g/24 h.

32. Adenosine deaminase deficiency
+ ADA is the enzyme which convert
Adenosine into Inosine
+ ADA deficiency leads to Severe
Combined Immunodeficiency (SCID)
+ In SCID, T & B lymphocytes donot
develop properly.

33. GOUT
+ High serum levels of urate induces gout
+ It causes inflammation of the joints by precipitation
as sodium urate crystals.
+ Drug: Allopurinol
+ This drug has a similar structure of xanthine and
acts by inhibiting the enzyme xanthine oxidase
+ Hence inhibition of the activity of xanthine oxidase
inhibits uric acid synthesis.

34. PYRIMIDINE NUCLEOTIDE –
DEGRADATION
+ The pathways for degradation of pyrimidines
generally lead to NH4+ production and thus to urea
synthesis.
+ The carbons of thymine are degraded to
succinyl-CoA; those of cytosine and
uracil are degraded to acetyl-CoA

37. SALVAGE PATHWAY
+ Purine and pyrimidine bases are recycled by salvage pathway
+ Free bases are constantly released in cells during the metabolic
degradation of nucleotides
+ These free bases are reused to make nucleotides, In a pathway simpler
than the de novo synthesis.
E.g.;
Adenine + PRPP
AMP + Pi
+ Reaction catalysed by adenosine Phosphoribosyltransferase
+ Phosphoribosyl pyrophosphate ( )

38. # Free guanine and hypoxanthine (the
deamination product of adenine) are
salvaged in the same way by
hypoxanthine-guanine
phosphoribosyltransferase. A similar
salvage pathway exists for pyrimidine
bases in microorganisms, and possibly in
mammals

39. Lesch-Nyhan syndrome
A genetic lack of hypoxanthine-guanine
phosphoribosyltransferase activity, seen
almost exclusively in young boys, results
in a set of symptoms called Lesch-Nyhan
syndrome.

41. REFERENCES
1) Lehninger’s Principles of Biochemistry – 8th Edition
2) Fundamentals of Biochemistry – 5th Edition; Donald Voet
& Judith G Voet
ACKNOWLEDGEMENT
+ All images are directly taken from different websites in Google