Nucleotide Metabolism Flashcards
What is the committed step in purine synthesis
Conversion of PRPP into phosphoribosylamine
If your body is consuming lots of ATP and has high levels of inorganic phosphate, how will that effect purine synthesis
It will increase the synthesis of purines to compensate for that additional need of ATP
How is folate used in purine synthesis
Part of it is used in the construction of IMP
IMP is the branch point in purine synthesis
How is balance of the concentration between the two pool of primary purines maintained
ATP and GTP are used for the construction of GMP and AMP, respectively
What is the rate limiting step in pyrimidine synthesis, and how is it regulated
Formation of carbamoyl phosphate by carbamoyl phosphate synthetase II
Allosterically activated by PRPP and inhibited by UTP/UMP
Aspartate transcarbamoylase forms carbamoyl aspartate- it is allosterically inhibited by CTP
UMP is made from what two molecules
PRPP and orotate
What is Orotic aciduria
Inability to convert orotic acid to UMP, causes megaloblastic anemia
What happens after UMP is formed
It is converted to UDP which is then either converted to dUDP or UTP
dUDP is converted to dUMP which is bridge to dTTP (thymidine) production
What is the branch point molecule in pyrimidine and purine synthesis
UDP in pyrimidine
IMP in purine
Which one, purine or pyrimidine synthesis, uses PRPP as a platform to construct the base on
Purine synthesis
Pyrimidines generate the base independently of PRPP
Methotrexate
Antineoplastic agent used to treat cancer
Prevents oxidation of NADPH by DHFR, disrupts DNA replication in rapidly dividing cells
Sulfa drugs
Competitively inhibit the bacterial enzyme that incorporates PABA into folate. Disrupts DNA replication in bacteria
How do drugs that deprive cells of GMP work (what do they target)
They target IMP dehydrogenase to prevent IMP from being formed, which is required for formation of GMP
What is the significance of the oxidation level of purines
Catabolic processes include steps where oxygen is added to molecules to make them more polar (more oxygen, further in the catabolic process)
ADA
Adenosine deaminase, plays important role in purine metabolism by catalyzing the irreversible step in the pathway
SCID
Invariably fatal genetic disorder where both B and T cells are crippled. Most common form is X-linked, second most common form is due to deficiency of purine catabolic enzyme ADA. This leads to a buildup of dADP and eventually blocks formation of all other dNDPs. Impairs DNA synthesis
Gout
Caused by either overproduction or, more commonly, underexcretion of uric acid. This causes deposits of sodium urate in the joints of the extremities or the kidneys. Treated with allopurinol which inhibits xanthine oxidase
General overview of pyrimidine catabolism
Converted to readily metabolized ketogenic or glucogenic, water soluble compounds
Uracil/cytosine are catabolized to what
Malonyl CoA
Thymine is catabolized to what
Succinyl CoA
Lesch-Nyhan syndrome
Results from defects in HGPRT in purine salvage pathway, leads to primary hyperuricemia and can cause gout, kidney stones, mental retardation
Acyclovir method of action
Thymidine kinase generates dTMP from dT. Acyclovir undergoes phosphorylation by viral thymidine kinase at a rate that exceeds that of cellular thymidine kinase. Acyclovir is eventually converted to GTP which is incorporated into viral cells, but lacks a 3’ hydroxyl group and terminates DNA replication
