Purine Metabolism Flashcards
What are the two subtypes of nucleotides?
Pyrimidines and purines
How many rings do purines have in their nitrogenous base?
Two rings
What is the major cellular source of energy?
ATP (adenosine triphosphate)
What does cyclic AMP stand for?
Cyclic adenosine monophosphate
True or False: Cyclic GMP serves as a second messenger.
True
What are exogenous nucleotides?
Nucleotides obtained from the diet
What are endogenous nucleotides?
Nucleotides synthesized by the body
What is the first step in purine synthesis?
Creation of PRPP (5 phosphoribosyl 1 pyrophosphate)
What does IMP stand for?
Inosine Monophosphate
What are the basic components of nucleotides?
Phosphate group, ribose sugar, base
What is the role of folate in purine synthesis?
Contributes single carbon groups
List the amino acids that provide nitrogen for purine synthesis.
- Glutamine
- Aspartate
- Glycine
What is the structure of purine bases?
Two rings with two nitrogen groups in each ring
What is the rate limiting enzyme in purine synthesis?
Glutamine PRPP amidotransferase
What distinguishes deoxyribonucleotides from ribonucleotides?
Deoxyribonucleotides lack a hydroxyl group
How does ribavirin affect purine synthesis?
Inhibits IMP dehydrogenase, reducing GMP synthesis
What is the function of mycophenolate?
Immunosuppressant that inhibits IMP dehydrogenase
What are the potential fates of free floating purine bases?
- Converted to uric acid
- Remade into nucleotides (purine salvage)
What enzyme is responsible for converting hypoxanthine or guanine to nucleotides?
HGPRT (hypoxanthine guanine phosphoribosyltransferase)
What does APRT stand for?
Adenine phosphoribosyltransferase
What chemotherapy drug mimics hypoxanthine and guanine?
6 mercaptopurine
What is Azathioprine converted to in the body?
6 mercaptopurine
What is the significance of PRPP in purine salvage?
Combines with free bases to regenerate nucleotides
What is the structure of Azathioprine similar to?
6MP
Azathioprine has an extra molecule that is removed in the body, resulting in 6MP.
What two purines are broken down into uric acid?
Hypoxanthine and guanine
These purines are converted to xanthine and then to uric acid for excretion.
What enzyme breaks down hypoxanthine into xanthine?
Xanthine oxidase
What enzyme converts guanine into xanthine?
Guanase
What is the role of adenosine deaminase?
Removes the amine group from adenosine and converts it into inosine
What condition is associated with deficiency in adenosine deaminase?
Severe combined immunodeficiency syndrome
What is gout?
A condition caused by excess uric acid in the plasma
What are common symptoms of gout?
Pain, swelling, and redness in joints
What is a classic location for gout symptoms?
Base of the big toe
What can trigger a gout attack?
Under excretion or overproduction of uric acid
What dietary factors can contribute to gout?
Consumption of purine-rich foods like meats and seafood
What medication is used to treat gout?
Allopurinol
What does allopurinol inhibit?
Xanthine oxidase
What are the potential effects of co-administering allopurinol with azathioprine or 6MP?
Increased effects and toxicity of 6MP
This occurs because allopurinol inhibits the metabolism of these drugs.
What is Lesch Nyhan syndrome?
A rare disorder caused by absence of the HGPRT enzyme
What results from the absence of the HGPRT enzyme?
Inability to salvage purines, leading to excess uric acid
What are the neurological symptoms associated with Lesch Nyhan syndrome?
Hypotonia and choreo
What behavior is commonly observed in children with Lesch Nyhan syndrome?
Self-mutilating behavior
What is a classic presentation of Lesch Nyhan syndrome?
A male child with motor symptoms, self-mutilation, and gout
Fill in the blank: Adenine is first converted back into the nucleotide _______.
Adenosine monophosphate
What happens to inosine in the purine breakdown pathway?
It is converted into hypoxanthine
What is the metabolic pathway that ramps up in Lesch Nyhan syndrome?
De novo purine synthesis pathway