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METABOLISM
Purine Synthesis
Pyrimidine: Thymine,
Cytosine& Uracil
Nucleotide = Nucleoside +
phosphate
DNA & RNA contain the same purine bases: Adenine and
Guanine.
DNA & RNA contain the pyrimidine Cytosine, but differ in the
second pyrimidine base: DNA contain thymine (T) whereas
RNA contain Uracil (U).
Importance
Storage & transmission of genetic information from
generation to generation
Adenosine phosphoribosyl
transferase (APRT) and hyoxanthine
guanine phosphoribosyl transferase
(HGPRT).
3. Purine nucleoside
phosphorylase converts
inosine & guanosine into their
respective purine bases;
hypoxanthine & xanthine
5. Hypoxanthine is oxidized by
xanthine oxidase to xanthine,
which is further oxidized by
xanthine oxidase to uric acid,
the final product of human
purine degradation. Uric acid
is excreted in the urine.
DISORDERS OF PURINE CATABOLISM
ADENOSINE DEAMINASE DEFICIENCY:
1. Causes severe combined immunodeficiency involving T-cell & B-cell dysfunction.
This is because there is accumulation of deoxyadenosine which increases
adenosylhomocysteine, this substance is toxic to immature lymphocytes resulting in
immunocompromised immune system.
2. Extremely large buildups of dATP in red cells (this dATP inhibits ribonucleotide
reductase, and therefore DNA synthesis).
3. dGTP is the major nucleotide that accumulates in red cells (dGTP is converted to
dATP, an inhibitor of ribonucleotide reductase. dGTP also inhibits the reduction of
UDP & CDP)
GOUT:
1. Characterised by hyperuricemia, with recurrent attacks of acute arthritic joint
inflamation caused by uric acid crystals deposition.
2. Primary gout (hyperuricemia) is the form of the disease that is attributable to an in-
born error of metabolism, such as overproduction of uric acid.
GOUT Contd.:
3. Secondary hyperuricemia may be caused by other diseases, for
example, cancer, chronic renal insufficiency, HGPRT deficiency, e.t.c.
HYPOURICEMIA
1. Hypouricemia and increased excretion of hypoxanthine and xanthine
are associated with xanthine oxidase deficiency due to a genetic
defect or to severe liver damage.
LESCH-NYHAN SYNDROME
1. Lesch-Nyhan Syndrome is a inherited disorder associated with a
virtually complete deficiency of hypoxanthine-guanine
phosphoribosyltransferase, and therefore inability to salvage
hypoxanthine or guanine.
The sources of the carbon and nitrogen atoms in the pyrimidine ring are
glutamine, CO2, and aspartic acid.
This is further
broken down by
phosphodiesterase,
producing
mononucleotides.
Nucleotidase
removes Phosphate
group hydrolytically.
Nucleosidase
degrade the
nucleosides to free
bases; purines &
pyrimidines