Molecular Biochemistry (Purine Metabolism) Flashcards
Nucleotide cyclic AMP
- Cyclic Adenosine MonoPhosphate
- Increase and decrease in blood flow
Nucleotide cyclic GMP
- Cyclic Guanosine MonoPhosphate
- Second messenger
RNA
- Its always synthesized first and then is converted to DNA by removing an OH group
Nitrogen group
- Comes from amino acids
Purine synthesis (ingredients)
- goal is to create AMP and GMP
1- Ribose phosphate sugar
2- Amino acids
3- Carbons
Purine Synthesis (Step 1: create PRPP)
- 5’-Phosphoribosyl-1-pyrophosphate
- Comes from 5-Ribose Phosphate
Purine Synthesis (Step 1: create IMP)
- Inosine monophosphate
- Is intermediate form of a nucleotide needed to form nucleotides the DNA and RNA use
- The base that use is called hypoxanthine
Purine bases
- two rings with two nitrogens
1. Adenine
2. Guanine
3. Hypoxantine
Nitrogen sources and others
- Glutamine
- Aspartate
- Glycine
- Folate (single carbon donor)
- CO2
Deosyribonucleotides
1- First synthesizes diphosphate version of purine nucleotides:
- ADP
-GMP
2- Ribonucleotide reductase remove the hydroxyl group
-deoxyADP
-deoxyGDP
Ribavirin (antiviral)
- Inhibit IMP dehydrogenase
- Blocks convertion of IMP to GMP (guanine nucleotides)
- Don’t let the virus to replicate their gene
Mycophenolate (immunosuppressant)
- Inhibit IMP dehydrogenase in WC
Purine Fates
- The bases (adenine, guanine, and hypoxantine) can be converted to uric acid or can remake nucleotides –> purine salvage
Purine Salvage
- Adenine back to AMP
- Guanine back to GMP
- Hypoxanthine back to IMP
- NEEDS PRPP
HGPRT (hypoxanthine-guanine phosphoribosyltransferase )
- Combines Hypoxantine and Guanine with PRPP in order to get IMP and GMP
APRT (adenine phosphoribosyltransferase)
- Combines Adenine with PRPP in order to get AMP
6-Mercaptopurine
- Chemotherapy agent
- Mimics hypoxantine/guanine
- Added to PRPP by HGPRT
- Forms thioinosiniacid
- Decrease levels of IMP, AMC, GMP
- Metabolized by XO
Azathioprine (immunesuppressant)
- Converted to 6-MP
- Metabolized by XO
Purine Breakdown (hypoxanthine)
- the enzyme xanthine oxidase break down:
hypoxanthine to xanthine
xanthine –> uric acid
Purine Breakdown (guanine)
- the enzyme guanase:
guanine –> xanthine
xanthine –> uric acid (xanthine oxidase)
Purine Breakdown (adenine)
- 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)
Severe combined immunodeficiency (SCID)
- Defects in purine degradation
- Adenosine deaminase (ADA) deficiency
Goat
- 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
Lesch-Nyhan Syndrome
- 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