L32- Purine Metabolism Flashcards
The nitrogen atoms in purines come from which amino acids?
Glycine, glutamine and aspartate.
In which organ does the de novo synthesis of purines primarily occur?
Liver.
PRPP, or 5-phosphoribosyl-1-pyrophosphate, is an important intermediate in the biosynthesis of both purines and pyrimidines. What is its immediate precursor?
Ribose-5-phosphate.
Which enzymes are involved in the conversion of ribose-5-phosphate to 5-phosphoribosylamine?
PRPP synthetase and glutamine PRPP amidotransferase.
Which enzyme catalyzes the formation of 5-phosphoribosyl-1-pyrophosphate (PRPP) from ribose-5-phosphate and ATP?
PRPP synthetase.
What is the committed step in the de novo biosynthesis of purines?
The conversion of PRPP to 5-phosphoribosylamine by glutamine PRPP amidotranferase.
The amine group on 5-phosphoribosylamine comes from which amino acid?
Glutamine.
How many molecules of ATP are required for the formation of inosinate (IMP) from 5-phosphoribosylamine?
4 ATP molecules are required.
Which form of tetrahydrofolate (THF) is required for the formation of inosinate (IMP) from 5-phosphoribosylamine?
N10-formyl-tetrahydrofolate.
What is the first purine to be synthesized in the de novo biosynthesis of purines?
Inosinate (IMP).
The synthesis of AMP from IMP requires ____ as an energy source and _____ as an amino group donor.
GTP; aspartate.
The synthesis of GMP from IMP requires ____ as an energy source and _____ as an amino group donor.
ATP; glutamine.
True or False. The conversion of monophosphate nucleosides to diphosphate nucleosides is catalyzed by kinases that are sugar-specific but not base-specific.
False. The conversion of monophosphates to disphosphates is catalyzed by kinases that are base-specific but not sugar-specific.
Which broad-specificity enzyme catalyzes the interconversion of diphosphate nucleosides with triphosphate nucleosides?
Nucleoside diphosphate kinase.
The carbon atoms in purines come from which compounds?
Carbon dioxide, N10-formyl THF and glycine.
Which amino acid contributes both nitrogen and carbon atoms in the de novo biosynthesis of purines?
Glycine.
In which cellular compartment does the synthesis of purines occur?
Cytosol.
In which tissue(s) does the salvage pathway for purine biosynthesis primarily occur?
Mostly in extrahepatic tissues.
What are the substrates and products of the reaction(s) catalyzed by hypoxanthine-guanine phosphoribosyl transferase (HGPRT)?
HGPRT is involved in the salvage pathway of purine biosynthesis. It catalyzes the formation of GMP from a guanine base and PRPP, and the formation of IMP from a hypoxanthine base and PRPP.
Which enzyme in the salvage pathway of purine biosynthesis catalyzes the formation of AMP from an adenine base and PRPP?
Adenine phosphoribosyl transferase (APRT).
What is the predominant direction and products of the reaction catalyzed by purine nucleoside phosphorylase?
The predominant direction is degradative (as opposed to base salvaging) and produces a free base and ribose-1-phosphate.
What class of enzymes is able to hydrolyze nucleotides from the diet or tissue breakdown to form nucleosides?
Phosphatases.
True or False. The enzyme adenosine deaminase can deaminate adenosine, 2’-deoxyadenosine and other 6-aminopurines.
True.
What is the product formed by the deamination of adenosine by adenosine deaminase?
Inosine.
What products are formed from the breakdown of inosine by purine nucleoside phosphorylase?
Hypoxanthine and ribose-1-phosphate.
What is the function of xanthine oxidase in purine catabolism?
It oxidizes hypoxanthine to uric acid in two steps.
The enzyme xanthine oxidase converts hypoxanthine to uric acid in two steps. What is the product of the first step?
Xanthine.
What is the common intermediate in the production of uric acid from hypoxanthine and guanine?
Xanthine.
The enzyme guanine deaminase catalyzes the deamination of guanine. What is the product of this reaction?
Xanthine.
Regulation of the de novo synthesis of purines occurs at which steps?
At the PRPP synthetase reaction, the PRPP amidotransferase reaction, and at the formation of AMP and GMP from IMP.
Name the inhibitor(s) of PRPP synthetase.
PRPP synthetase is subject to feedback inhibition by AMP, ADP, ATP, GMP, GDP, and GTP.
Name the allosteric inhibitor(s) of PRPP amidotransferase.
AMP and GMP.
What condition can result from the overproduction of purines or the decreased excretion of uric acid?
Gout.
Allopurinol is a competitive inhibitor of which enzyme?
Xanthine oxidase.
Which hypoxanthine analogue is effective in lowering the levels of uric acid in the blood, and can therefore be used to treat gout?
Allopurinol.
Which purine derivative acts as a hypoxanthine analogue and is commonly used to treat acute leukemias?
6-mercaptopurine.
How does a partial defect in HGPRT lead to gout?
It causes reduced IMP and GMP formation via the salvage pathway. As a result, there is reduced feedback inhibition of the de novo pathway, leading to accumulation of PRPP.
Which enzyme may lose its sensitivity to feedback inhibition by purine nucleotides, resulting in an overproduction of PRPP that may in turn lead to gout?
PRPP synthetase.
Which enzyme deficiency can lead to gout due to an overproduction of ribose-5-phosphate?
Glucose-6-phosphatase deficiency.
What is the enzymatic defect that leads to Lesch-Nyhan syndrome?
Lack of functional HGPRTase, resulting in an increase in purine synthesis via the de novo pathway.
What condition can result from adenosine deaminase deficiency?
Severe combined immunodeficiency syndrome (SCID), a condition in which patients lack both B and T lymphocyte functions.
What class of antibiotics interferes with folate synthesis in bacteria by functioning as p-aminobenzoic acid analogues?
Sulfonamides.
