DEGRADATION OF

NUCLEOTIDES
Submitted by – Poornima
MSc Zoology Previous
2223
Submitted to - Dr Minakshi Sharma Mam
Introduction
NUCLEOTIDE
•Basic building block of nucleic acids (DNA/RNA)
•Consists of nucleoside and phosphate group
•Nucleoside consist of sugar and Nitrogenous base which can be
purine or pyrimidine
NUCLEOTIDE DEGRADATION
•Nucleotide degradation occurs in liver, small intestine
•Two degradation occur purine degradation and pyrimidine
degradation involving various processes like dephosphorylation,
deamination, oxidation, reduction
Overview of nucleotide degradation
Purine degradation
• It starts with nucleotide
AMP, IMP, XMP, GMP and
the end product is uric acid
• They are converted to their
respective nucleosides by
5’nucleotidase and reaction
called dephosphorylation
• Deamination of adenosine
occurs by adenosine
deaminase to produce
inosine
• Phosphorolysis of inosine to
produce hypoxanthine
• Oxidation of hypoxanthine
to form xanthine which is
further oxidated to form
uric acid
• GMP undergoes similar steps to produce uric acid
Animals oxidise uric acid to different excretory products
SALVAGE PATHWAY
• Recycling of bases and
formation of nucleotide
• Important in RBCs and
brain where de novo
pathway do not occur
• PRPP is starting
material which reacts
with Nitrogenous base
to form nucleotide using
HGPRT
Disorders of purine degradation
• GOUT-increase in levels of uric acid(hyperuricemia) and leads to
deposition of monosodium urate crystals in joints and thus causing
arthritis.
TWO TYPES-
Primary gout(inborn error of metabolism, genetic and caused by
HGPRT deficiency, elevated purine synthesis by PRPP synthetase)
Seconadry gout(due to various diseases which cause increased synthesis
or decreased excretion of uric acid like leukemia, starvation, psoriasis)
TREATMENT-allopurinol drug, colchicine, probenacid increase uric
acid excretion, drink more water
• LESCH NYHAN
SYNDROME – due to
HGPRT deficiency ,
purine synthesis is
incresed beacause of
PRPP accumulation and
uric acid elevated in
blood. Victims experience
severe arthritis,
retardation and other
neurological symptoms.
• SCID(severe combined immunodeficiency)
ADA(adenosine deaminase) deficiency leading to disorders
involving diminished immune responses because adenosine is
not deaminated to inosine
Adenosine increases and uric acid synthesis decreased
T cells and B cells dysfunctions
Can be treated by ADA gene transfer
Pyrimidine degradation
• Undergoes similar reactions like dephosphorylation, deamination,
cleavage of glycosidic bond to liberate Nitrogenous bases.
• Bases are then degraded to highly soluble products like beta alanine
and beta aminoisobutyrate and ammonium ion, CO2 also produced.
• Starts with CMP, UMP, TMP which are converted to their
respective nucleosides by nucleotidase(dephosphorylation)
• Deamination of cytidine to form uridine
• Phosphorolysis of uridine
to uracil by
phosphorylase

• Reduction of uracil by
dihydrouracil
dehydrogenase to
dihydrouracil
• Hydrolysis of
dihydrouracil by
dihydropyrimidinase to
beta uriedopropionate

• Again hydrolysis by beta

ureidopropinase to beta
alanine and NH4, CO2 also
produced
• Thymine undergoes similar steps but only end
product is different
• Beta alanine and beta aminoisobutyrate are further
converted through transamination and other
activation reactions to malonyl coA and
methylmalonyl coA
• Ammonium ion produced enters urea cycle forming
urea
Disorders of pyrimidine degradation
OROTIC ACIDURIA-
• Autosomal recessive disorder
• results from absence of orotate phosphoriboxyl
transferase(OPRTase) and OMP decarboxylase
• Excretion of orotic acid in urine which cause severe anemia
and retards growth
• Allopurinol may also lead to orotic aciduria
• Can be treated by eating diet rich in uridine or cytidine
REYE’S SYNDROME –
• Also known as secondary orotic aciduria
• Defect in ornithine transcarboxylase which causes
accumulation of carbomyl phosphate which leads to
increase in synthesis of orotic acid
References
1. Priciples of biochemistry by lehninger
2. Principles of biochemistry by voet & voet
3. Biochemistry by satyanarayana
4. www.slideshare.net
5. Watcut.Uwaterloo.ca
6. www.ncbi.nlm.nih.gov