10. Nucleotide Metabolism Flashcards
For de-novo purine nucleoside synthesis, what is synthesized first - the sugar or the purine?
The sugar molecule first
(pure sugar)
Methotrexate inhibits what enzyme important to purine synthesis?
Dihydrofolate Reductase
Inosine Mono-Phosphate (IMP) is an important intermediate in the synthesis of what nucleotides?
AMP and GMP
(Inosine is INO[cent] and PURE[-ine]
Inosine makes the purines)
Why is Methotrexate such an effective inhibitor of Dehydrofolate Reductase?
Its structure is nearly identical
BUT
It has 100x more affinity for folate enzymes (like DHFR) than folate does!
Sulfonamides inhibit what bacterial pathway that isn’t present in humans?
Folate synthesis!
(Specifically the bacterial enzyme that incorporates PABA into Folate)
Pathways that produce ATP, might stimulate the synthesis of what nucleotide?
GMP
(High energy purine nucleotides stimulate synthesis of the low energy version of the other purine. GTP/AMP ATP/GMP)
For de novo Pyrimidine synthesis, which is made first - the sugar or the pyrimidine?
The Pyrimidine first.
(Pyrimitive me-first mentality)
Carbamoyl phosphate and aspartate come together to form an intermediate in the synthesis of which nucleobase type?
What is special about this step?
Pyrimidines
It is the committed step of pyrimidine synthesis.
Where does pyrimidine synthesis occur?
Partially in the cytosol, partially in the mitochondria.
What does Adrucil do that makes it useful in pancreatic, colorectal, ovarian, gastric and breast cancers?
Inhibits DNA production. Mechanism of action is not entirely clear, but it is likely to involve inhibition of thymidylate synthase.
What enzyme catalyzes the first step (activation of ribose 5-P) in purine synthesis?
PRPP synthetase (makes PRPP, which is activated R5P)
What is the committed step of Purine synthesis?
What enzyme catalyzes this reaction?
PRPP ⇒ PRA (Activated R5P -> Activated R5P with NH2 on it)
(get ready)
Glutamine:phosphoribosyl pyrophosphate amidotransferase
(purines are elitists, so their commited step has to have a super ostentatious name)
What is the committed step of Pyrimidine synthesis?
(What are the reactancs and the product? What enzyme?)
Carbamoyl Phosphate + Aspartate -> N-Carbamoylaspartate (the pyrimidine ring)
-Aspartate transcarbamoylase-
What is the enzyme target of 5-fluorouracil (Adrucil)?
Thymdylate Synthase
What enzyme is deficient in orotic aciduria?
What is the treatment?
UMP Synthase
Oral Uridine
What is the enzyme target for Acyclovir?
Thymidine Kinase
In purine catabolism, what is the common landing point for both GMP and AMP?
Xanthine
(which is then converted to Uric Acid)
What enzyme is the target of allopurinol?
Xanthine oxidase
(Which actually causes a backup of Hypoxanthine - which is more soluable than uric acid.)
What enzyme catalyzes Adenosine to Inosine?
What does an excess of this enzyme cause?
What does a deficiency cause?
Adenosine Deaminase
Hemolytic Anemia
SCID
What is the clinical relevance of beta-aminoisobutyrate?
Estimation of nucleotide turnover / nucleotide homeostasis.
What enzyme deficiency can cause renal lithiasis?
APRT
(You want to tear yourself APRT to get to the kidney stones)
What enzyme deficiency is named Lesch-Nyhan syndrome?
What do you find elevated in the blood and urine?
What are the symptoms?
HGPRT
Uric acid
Urate kidney stones, ataxia, mental deficiency, self mutalation. :(
