Nucleotide Metabolism

Question 1

What is a general difference between de novo synthesis of purines and pyrimidines?

Answer 1

Purine - Start from the pentose sugar and slowly build the purine ring

Pyrimidines - Build pyrimidines ring, then attach to the sugar at the end

Question 2

What/describe is the first step of purine synthesis?

Answer 2

Ribose 5 phosphate > PRRP With the use of PRRP synthase, ATP, Mg+2, Pi, and ATP

This is a regulated step - negative feedback loop by purine nucleotides.

Question 3

What/describe the second step of purine de novo synthesis?

Answer 3

PRRP > 5-Phosphoribosylamine With PPRP Glutamyl Amidotransferase, and Glutamine

-Committed and regulated step, negative feedback back purine nucleotides (end product) and positive by PRRP

Question 4

What steps in purine synth is Glutamine used in the reaction and turned to glutamate?

Answer 4

Steps 2 (PPRP Amidotransferase) and 5 (ATP and mg2+)

And 15 (along with ATP) in process of turning IMP to GMP

Question 5

What steps is Folate used in purine synth?

Answer 5

4 - N5-N10-methenyl-H4 folate > H4 folate (THF) -transfers methyl Enzyme: formyltransferase

Question 6

What structure is made after step 11 of purine synth and can produce either GMP or AMP?

Answer 6

IMP - Inosine monophosphate is a nucleotide (base-sugar-phosphate)
The base is hypoxanthine
Nucleoside (base-sugar) is called inosine

Question 7

What are two inhibitors of purine synth and how do they work?

Answer 7

1. Glutamine analogs - ex. Azarine (too toxic to use in clinical setting) blocks steps 2, 5, and 15
2. Inhibitors of Folate metabolism - sulfonamides (PABA to folic acid) and methotrexate (folic acid to THF, dehydrofolate reductase) blocks steps 4 and 10

Competitive antagonists

Question 8

What two diseases occur from lack of folic acids?

Answer 8

A cephalon and Spinal bifida Neural tube defects

Question 9

What/describe three types of purine salvage?

Answer 9

1. Phosphorylation of purine nucleosides - adenosine > AMP (adenosine kinase, ATP)
2. Phosphorylation of free bases - adenine > AMP (APRT, PRPP)
   - hypoxanthine or guanine > IMP or GMP (HGPRT, PRPP)

Question 10

What is Lesch-Nyhan syndrome?

Answer 10

X-linked recessive purine overproduction

• causes gout and kidney stones, neurological problems, mental retardation, self mutilation
• affects HGPRT enzyme of purine salvage of IMP and GMP, causes PRPP excess and overproduction of purine

Question 11

What are 3 inhibitors of purine degradation? Describe them

Answer 11

1. ADA deficiency (SCID) - inhibits adenosine deaminase, causes not T or B cells, gene therapy for treatment
2. Purine Nucleoside Phosphorylase deficiency causes immuno disorder - autosomal recessive, no T cells
3. Xanathine oxidase inhibited by Allopurinal, med against uric acid build up conditions like gout

Question 12

Describe the first step pyrimidine de novo syn?

Answer 12

CO2 + Glutamine + ATP > Carbamoyl Phosphate (CAP)

Enzyme: Carbamoyl phosphate synthase II

Question 13

What is the inhibitor for pyrimidine synth and what specific enzyme does it inhibit? Describe the process

Answer 13

Thymidylate synthase is inhibited by 5-fluorouracil derivatives - ?

NEEED TO FINISH

Question 14

What are two processes of salvaging pyrimidine nucleosides?

Answer 14

Uridine or Cytidine > UMP or CMP (Uridine-Cytidine kinase, ATP)

Thymidine > TMP (Thymadine Kinase (TK), ATP)