metabolism of nucleic acid
nucleic acid = polynucleotide = nucleotide = nucleoside = sugar + base
all 4 N atoms of purine from amino acids
2 from glutamine, 1 from aspartate, 1 from glycine
all 5 C atoms come from
2 glycine, 2 tetrahydrofolate , 1 co2
de novo biosynthesis of purine in liver
PRPP = inosine 5 monophosphate IMP = adenylsuccinate = adenosine AMP
= Xanthosine 5 phosphate XMP =guanosine GMP
salvage reaction
conversion of purine to mononucleotides
require less enrgy compare to de novo biosynthesis
adenine + PRPP = AMP + PPi
guanine + PRPP = GMP + PPi
hypoxanthine + PRPP = IMP + PPi
adenosine + ATP = AMP+ ADP
guanosine + ATP = GMP + ADP
biosynthesis of pyrimidine simpler because one ring simple structure
1 mole glutamine,ATP,CO2,aspartate = OMP = UMP uridine monophosphate
salvage reaction :
thymidine + ATP =TMP + ADP
uridine + ATP = UMP + ADP
cytidine + ATP = CMP + ADP
orotic acid + PRPP = OMP + PPi
differences . for pyrimidine, PRPP is added first to form OMP
no branch in de novo, precursor diff
ribonucleoside diphosphates reduced to 2-deoxyribonucleoside diphosphate in all organism
NADPH Is reducing agent
majority nucleotide form by de novo or salvage are ribonucleotide reductase
cancer chemotherapy = inhibit formation of dTTP thus DNA cancer cells cause its death
catabolism of pyrimidine
CO2 NH3 beta alanine beta-aminoisobutyrate
end product for
thymine : CO2, NH3, beta aminoisobutyrate
cytosine: CO2, NH3, beta alanine
Disorder,overproduction cause by
deficiency of urea cycle enzyme ornithine transcarbamoylase
high nitrogen food
drug effect
type 1 orotic aciduria
treatment of orotic aciduria
uridine/cytidine increase UMP production
UMP inhibit CPS ll thus attenuating orotic acid production
catobolism of purine
adenosine = inosine = hypoxanthine = xanthine = uric acid
guanosine = guanine = xanthine = uric acid
disorder of purine metabolism
gout cause by excess PRPP and deficiency HGPRT, renal disorder lead to accumulation of uric acid
big toe, inflammatory , pain, stiffness, swelling.
diagnosis: uric acid cyrstal, blood test , urine test
treatment: NSAIDs, corticosteroids, allopurinol
lesch-nyhan , deficiency of HGPRT cause increase production of uric acid, accumulation os stones and gout . bite off fingertips and part of lips.
von gierke , increase PRPP
hypouricemia cause by xanthine oxidase deficiency
