Chp 22 Flashcards
What is the role of PRPP and what substances regulate it?
PRPP is a key molecule in nucleotide metabolism. It is activated by inorganic phosphate (Pi) and inhibited by end products like AMP, GMP, and IMP
Which bond rotation in the nucleoside structure relates to syn and anti-conformations of nucleotides and nucleic acids?
These conformations relate to the rotation around the glycosidic bond (the bond between the nitrogenous base and the ribose/deoxyribose sugar).
Which atom does glutamine donate in the synthesis of IMP?
Glutamine donates nitrogen for the synthesis of IMP.
What are the precursors for the biosynthesis of purine rings?
Purine rings are constructed from amino acids (aspartate, glycine, glutamine), CO₂, and N10-formyl-THF.
What are the precursors for the biosynthesis of pyrimidine rings?
Pyrimidine sources include glutamine, CO₂, and aspartate.
What nucleotides is Inosinate a precursor for?
AMP and GMP.
Outline the differences between de novo purine and pyrimidine nucleotide biosynthesis.
Purine synthesis: The purine ring is built step by step onto ribose 5-phosphate. Starts with PRPP and adds atoms to form IMP. Pyrimidine synthesis: The pyrimidine ring is synthesized first, then attached to ribose 5-phosphate. Ends with UMP, which is converted to other pyrimidine nucleotides.
How are AMP and GMP involved in the regulation of PRPP?
PRPP synthetase is inhibited by AMP and GMP.
What are the key regulations introduced for purine nucleotide synthesis?
PRPP synthetase is activated by Pi, inhibited by AMP, GMP, IMP. GPAT stops when AMP or GMP is high.
What are the key regulations introduced for pyrimidine nucleotide synthesis?
CPSII is inhibited by UTP, activated by PRPP.
Give the names of the key enzymes involved in purine nucleotide synthesis.
PRPP synthetase, GPAT, nucleotide kinases.
Give the names of the key enzymes involved in pyrimidine nucleotide synthesis.
CAD (CPSII, aspartate transcarbamoylase, dihydroorotase), UMP synthase, CTP synthetase.
In purine salvage, deficiency of which enzyme will lead to Lesch-Nyhan syndrome?
Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT).
What is the end product of purine degradation and its role in gout?
The end product of purine degradation is uric acid. Gout occurs due to monosodium urate crystal deposition in joints/soft tissues.
Outline what is introduced for the formation of deoxyribonucleotides from ribonucleotides.
Deoxyribonucleotides are synthesized from ribonucleoside diphosphates (e.g., CDP, UDP) by ribonucleotide reductase. Key enzyme: Ribonucleotide reductase (reduced by sulfhydryl groups). Key steps: Reduction of ribose to deoxyribose. dUMP is converted to dTMP by thymidylate synthase (with N⁵,N¹⁰-methylene-THF as the methyl donor). Regulation: Inhibited by dATP, activated by ATP, regulated by nucleoside triphosphates binding to allosteric sites.
