Chapter 18: Purine and Pyrimidine Metabolism Flashcards
Ribose 5 phosphate uses what enzymes, etc to create PRPP?
ribose 5-P uses addition of pyrophosphate from ATP and PRPP synthetase to create PRPP (phosphoribosyl pyrophosphate)
Cells synthesize nucleotides in what 2 ways?
- de novo synthesis
- salvage pathway
Where does de novo synthesis of nucleotides occur?
What organ?
predominantly in the liver
What is a nucleoside?
consisting of a purine or pyrimidine base linked to a sugar.
Explain de novo synthesis of purines and pyrimidines.
purines and pyrimidines are synthesized from smaller precursors, and PRPP is added to the pathway at some point
Explain the salvage pathway in synthesis of nucleotides.
preformed purine and pyrimidine bases can be converted into nucleotides by salvage enzymes distinct from those of de novo synthesis
Where do purine and pyrimidine bases for salvage enzymes arise from in the salvage pathway?
- synthesis in the liver and transport to other tissues
- digestion of endogenous nucleic acids (cell death, RNA turnover)
Which pathway, de novo or salvage, is most essential for adequate nucleotide synthesis?
salvage pathway
What is the absent or deficient enzyme in Lesch Nyhan disease?
hypoxanthine guanine phosphoribosyl pyrophosphate transferase, (HGPRT)
aka (HPRT)
What are some symptoms of Lesch Nyhan disease?
CNS deterioration,
intellectual disability,
and spastic cerebral palsy
associated with compulsive self mutilation (biting of hands and lips)
hyperuricemia
death usually in first decade
Why do patients have CNS dysfunction with Lesch-Nyhan disease?
cells in the basal ganglia of the brain (fine motor control) normally have very high HGPRT activity
Why do patients with Lesch-Nyhan disease have hyperuricemia?
because purines cannot be salvaged causing gout
Draw out a diagram for nucleotide synthesis by salvage and de novo pathways.
Refer to diagram
Pyrimidines are synthesized de novo in what part of the cell?
cytoplasm
Where is CPS I located in cells compared to CPS II?
CPS I in the mitochondria of cells while CPS II is in the cytoplasm
What can be added to an infants formula to aid in UMP synthase deficiency?
uridine
Orotic aciduria inheritance pattern?
AR
How does addition of uridine to baby formula help relieve orotic acid formation in the urine of an infant with orotic aciduria?
uridine is salvaged to UMP, which feedback-inhibits carbamoyl phosphate synthetase -2, preventing orotic acid formation
DD of orotic aciduria with hyperammonemia (no megaloblastic anemia). Name the pathway involved and the deficient enzyme.
Pathway: urea cycle
Enzyme deficient: OTC
What is the DD of orotic aciduria with megaloblastic anemia (no hyperammonemia). Name the pathway and enzyme that is deficient.
Pathway: pyrimidine synthesis
Enzyme deficient: UMP synthase
DD of megaloblastic anemia with no orotic aciduria?
folate or B12 deficiency
Be able to create a diagram for de novo pyrimidine synthesis. (include where antineoplastic drugs work)
Refer to diagram
Cotrimoxazole is a mix of what antibiotics that act synergistically?
sulfamethoxazole and trimethoprim
What enzyme does sulfamethoxazole inhibit?
dihydropteroate synthase (we don’t have this enzyme we need folic acid from diet.)
