10. Nucleotide Metabolism

Question 1

For de-novo purine nucleoside synthesis, what is synthesized first - the sugar or the purine?

Answer 1

The sugar molecule first

(pure sugar)

Question 2

Methotrexate inhibits what enzyme important to purine synthesis?

Answer 2

Dihydrofolate Reductase

Question 3

Inosine Mono-Phosphate (IMP) is an important intermediate in the synthesis of what nucleotides?

Answer 3

AMP and GMP

(Inosine is INO[cent] and PURE[-ine]

Inosine makes the purines)

Question 4

Why is Methotrexate such an effective inhibitor of Dehydrofolate Reductase?

Answer 4

Its structure is nearly identical

BUT

It has 100x more affinity for folate enzymes (like DHFR) than folate does!

Question 5

Sulfonamides inhibit what bacterial pathway that isn’t present in humans?

Answer 5

Folate synthesis!

(Specifically the bacterial enzyme that incorporates PABA into Folate)

Question 6

Pathways that produce ATP, might stimulate the synthesis of what nucleotide?

Answer 6

GMP

(High energy purine nucleotides stimulate synthesis of the low energy version of the other purine. GTP/AMP ATP/GMP)

Question 7

For de novo Pyrimidine synthesis, which is made first - the sugar or the pyrimidine?

Answer 7

The Pyrimidine first.

(Pyrimitive me-first mentality)

Question 8

Carbamoyl phosphate and aspartate come together to form an intermediate in the synthesis of which nucleobase type?

What is special about this step?

Answer 8

Pyrimidines

It is the committed step of pyrimidine synthesis.

Question 9

Where does pyrimidine synthesis occur?

Answer 9

Partially in the cytosol, partially in the mitochondria.

Question 10

What does Adrucil do that makes it useful in pancreatic, colorectal, ovarian, gastric and breast cancers?

Answer 10

Inhibits DNA production. Mechanism of action is not entirely clear, but it is likely to involve inhibition of thymidylate synthase.

Question 11

What enzyme catalyzes the first step (activation of ribose 5-P) in purine synthesis?

Answer 11

PRPP synthetase (makes PRPP, which is activated R5P)

Question 12

What is the committed step of Purine synthesis?

What enzyme catalyzes this reaction?

Answer 12

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)

Question 13

What is the committed step of Pyrimidine synthesis?

(What are the reactancs and the product? What enzyme?)

Answer 13

Carbamoyl Phosphate + Aspartate -> N-Carbamoylaspartate (the pyrimidine ring)

-Aspartate transcarbamoylase-

Question 14

What is the enzyme target of 5-fluorouracil (Adrucil)?

Answer 14

Thymdylate Synthase

Question 15

What enzyme is deficient in orotic aciduria?

What is the treatment?

Answer 15

UMP Synthase

Oral Uridine

Question 16

What is the enzyme target for Acyclovir?

Answer 16

Thymidine Kinase

Question 17

In purine catabolism, what is the common landing point for both GMP and AMP?

Answer 17

Xanthine

(which is then converted to Uric Acid)

Question 18

What enzyme is the target of allopurinol?

Answer 18

Xanthine oxidase

(Which actually causes a backup of Hypoxanthine - which is more soluable than uric acid.)

Question 19

What enzyme catalyzes Adenosine to Inosine?

What does an excess of this enzyme cause?

What does a deficiency cause?

Answer 19

Adenosine Deaminase

Hemolytic Anemia

SCID

Question 20

What is the clinical relevance of beta-aminoisobutyrate?

Answer 20

Estimation of nucleotide turnover / nucleotide homeostasis.

Question 21

What enzyme deficiency can cause renal lithiasis?

Answer 21

APRT

(You want to tear yourself APRT to get to the kidney stones)

Question 22

What enzyme deficiency is named Lesch-Nyhan syndrome?

What do you find elevated in the blood and urine?

What are the symptoms?

Answer 22

HGPRT

Uric acid

Urate kidney stones, ataxia, mental deficiency, self mutalation. :(