Molecular Biochemistry (Purine Metabolism)

Question 1

Nucleotide cyclic AMP

Answer 1

• Cyclic Adenosine MonoPhosphate
• Increase and decrease in blood flow

Question 2

Nucleotide cyclic GMP

Answer 2

• Cyclic Guanosine MonoPhosphate
• Second messenger

Question 3

RNA

Answer 3

• Its always synthesized first and then is converted to DNA by removing an OH group

Question 4

Nitrogen group

Answer 4

• Comes from amino acids

Question 5

Purine synthesis (ingredients)

Answer 5

• goal is to create AMP and GMP
  1- Ribose phosphate sugar
  2- Amino acids
  3- Carbons

Question 6

Purine Synthesis (Step 1: create PRPP)

Answer 6

• 5’-Phosphoribosyl-1-pyrophosphate
• Comes from 5-Ribose Phosphate

Question 7

Purine Synthesis (Step 1: create IMP)

Answer 7

• Inosine monophosphate
• Is intermediate form of a nucleotide needed to form nucleotides the DNA and RNA use
• The base that use is called hypoxanthine

Question 8

Purine bases

Answer 8

• two rings with two nitrogens
  1. Adenine
  2. Guanine
  3. Hypoxantine

Question 9

Nitrogen sources and others

Answer 9

• Glutamine
• Aspartate
• Glycine
• Folate (single carbon donor)
• CO2

Question 10

Deosyribonucleotides

Answer 10

1- First synthesizes diphosphate version of purine nucleotides:
- ADP
-GMP
2- Ribonucleotide reductase remove the hydroxyl group
-deoxyADP
-deoxyGDP

Question 11

Ribavirin (antiviral)

Answer 11

• Inhibit IMP dehydrogenase
• Blocks convertion of IMP to GMP (guanine nucleotides)
• Don’t let the virus to replicate their gene

Question 12

Mycophenolate (immunosuppressant)

Answer 12

• Inhibit IMP dehydrogenase in WC

Question 13

Purine Fates

Answer 13

• The bases (adenine, guanine, and hypoxantine) can be converted to uric acid or can remake nucleotides –> purine salvage

Question 14

Purine Salvage

Answer 14

• Adenine back to AMP
• Guanine back to GMP
• Hypoxanthine back to IMP
• NEEDS PRPP

Question 15

HGPRT (hypoxanthine-guanine phosphoribosyltransferase )

Answer 15

• Combines Hypoxantine and Guanine with PRPP in order to get IMP and GMP

Question 16

APRT (adenine phosphoribosyltransferase)

Answer 16

• Combines Adenine with PRPP in order to get AMP

Question 17

6-Mercaptopurine

Answer 17

• Chemotherapy agent
• Mimics hypoxantine/guanine
• Added to PRPP by HGPRT
• Forms thioinosiniacid
• Decrease levels of IMP, AMC, GMP
• Metabolized by XO

Question 18

Azathioprine (immunesuppressant)

Answer 18

• Converted to 6-MP
• Metabolized by XO

Question 19

Purine Breakdown (hypoxanthine)

Answer 19

• the enzyme xanthine oxidase break down:
  hypoxanthine to xanthine
  xanthine –> uric acid

Question 20

Purine Breakdown (guanine)

Answer 20

• the enzyme guanase:
  guanine –> xanthine
  xanthine –> uric acid (xanthine oxidase)

Question 21

Purine Breakdown (adenine)

Answer 21

• Adenine is converted back to AMP by APRT
  MP group is removed then it becomes anenosine
  the enzyme adenosine deaminase removes the amine group from adenosine –> inosine (deamination)
  inosine –> hypoxanthine (Purine nucleoside phosphorylase)

Question 22

Severe combined immunodeficiency (SCID)

Answer 22

• Defects in purine degradation
• Adenosine deaminase (ADA) deficiency

Question 23

Goat

Answer 23

• Excess of uric acid (under excretion or overproduction)
• Crystal in joints (pain, swelling, redness)
• Treatment with allopurinol (inhibitor of xanthine oxidase)
• Don’t get along with 6-MP or Azathioprine –> toxicity

Question 24

Lesch-Nyhan Syndrome

Answer 24

• X-linked absence of HGPRT
• Purines can’t be salvage so they are shunted into uric acid
• Excess uric acid production
• Juvenile goat
• Excess of novo purine synthesis (PRPP and IMP)
• Neurological impairment
• Limited treatments

Question 25

Male child with motor symptoms, self-mutilation, gout, orange crystals in urine

Answer 25

Lesch-Nyhan Syndrome