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Where is the beta glycosidic linkage on a purine?
Where is the beta glycosidic linkage on a pyramidine?
PO4 is esterified to C5' of pentose. What does this make?
What are the functions of 5-phosphoribosyl-1-pyrophosphate (PRPP)?
Biosynthesis of purines, pyramidines, histidine, and tryptophan
Do patients with SCID (severe combined immunodeficiency disease), caused by an adenosine deaminase deficiency (ADA), have a deficiency in T cells or B cells?
Do patients with Purine Nucleoside Phosphorylase Deficiency (PNP) have a deficiency in T cells or B cells?
What are the three types of Purine Diseases?
- Immunodeficiency Diseases
- Erectile Dysfunction
How are purines numbered?
- N1 at 10:00. Counterclockwise in that ring
- Clockwise in other ring
How are pyramidines numbered?
N1 at 6:00, then clockwise
What is the difference between nucleotides and nucleosides?
- Nucleotides = 1 PO4
- Nucleosides = 2 or more PO4
What are the three pathways of purine metabolism?
- De novo (Biosynthetic)
- Catabolism (Catabolic)
- Salvage (Biosynthetic)
What is the end product of purine degradation?
What syndrome is characterized by extreme gout, including tophi, and neurological syndromes including ataxia and self-mutilation?
Which N is the sugar linked to in a purine?
Which N is the sugar linked to in a pyramidine?
What is the chemical name for Adenine?
What is the chemical name for Guanine?
What is the chemical name for Cytosine?
What is the chemical name for Uracil?
What is the chemical name for Thymine?
NMP + ATP yields what two products?
(reverse reaction also occurs)
NDP + ADP
NDP + ATP yields what two products?
(reverse reaction also occurs)
NTP + ADP
What is the only pathway of purine metabolism that occurs in the brain?
The short-term goal in the treatment of gout is?
Control of Inflammation
The main protein whose function is altered by uricosuric drugs is a?
Transport (carrier) Protein
Lysch-Nyhan Disease is due to the inability to catalyze what reaction?
Guanine to GMP
Adenylate (AMP) is synthesized in a two-step reaction sequence involving what three molecules?
- Inosinic Acid
What is the irreversible, rate-limiting step in purine synthesis?
A low Km Value means a high or low affinity?
What two molecules is PRPP (5-phosphoribosyl-1-pyrophosphate) synthesized from? What enzyme catalyzes this reaction? What activates this enzyme, and what inhibits it?
- Synthesized from ATP & Ribose 5-Phosphate
- Enzyme is PRPP Synthetase
- Activated by Inorganic Phosphate
- Inactivated by Purine Nucleotides (end-product inhibition)
In the second step of purine synthesis, what two molecules is 5'-phosphoribosylamine synthesized from? What enzyme catalyzes this reaction? What two products inhibit this enzyme?
**This is the _________ step in purine nucleotide biosynthesis.
- Synthesized from PRPP & Glutamine
- Glutamine:phosphoribosylpyrophosphate amidotransferase
- Inhibited by AMP & GMP (end-products of pathway)
Steps 3-12 of purine synthesis lead to the synthesis of what molecule, known as the "parent" purine nucleotide? What molecule does this pathway require as an energy source?
- Inosine Monophosphate (IMP)
In the thirteenth step of purine synthesis, IMP is converted to either _______ or ________. What molecule do each require as an energy source?
- AMP: requires GTP
- GMP: requires ATP
If both AMP and GMP are present in adequate amounts, the de novo pathway of purine synthesis is turned off at the ____________ step.
Purines that result from the normal turnover of cellular nucleic acids, or the small amount that is obtained from the diet and not degraded, can be converted to nucleoside triphosphates and used by the body. What is this referred to as?
The Salvage Pathway for Purines
What is the only purine nucleoside to be salvaged? What is it phosphorylated to (by adenosine kinase)?
What is the main enzyme involved in the Salvage Pathway? What does this enzyme use as its source of Ribose 5-Phosphate? The release of pyrophosphate and its subsequent hydrolysis by pyrophosphatase makes these reactions ___________.
- Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT)
Lesch-Nyhan is associated with an almost complete deficiency of what enzyme? This deficiency results in an inability to salvage _________ or _________, from which excessive amounts of uric acid are produced. In addition, the lack of this salvage pathway causes increased ______ levels and decreased IMP and GMP levels. As a result, amidotransferase has excess substrate and decreased inhibitors available, and de novo purine synthesis is _________.
- Hypoxanthine or Guanine
Ribonucleoside diphosphates are reduced to 2'deoxyribonucleotides by what three enzymes?
- Thioredoxin Reductase
- Ribonucleoside Disphosphate Reductase
In the formation of uric acid, an amino group is removed from AMP to produce _____ by AMP deaminase, or from adenosine to produce _________ (hypoxanthine-ribose) by adenosine deaminase. IMP and GMP are then converted into their nucleoside forms, ________ and ________, by the action of 5'-nucleotidase. Purine nucleoside phosphorylase then converts inosine and guanine to their respective purine bases, __________ and ____________. Guanine is deaminated to form _________. Hypoxanthine is oxidized by xanthine oxidase to form __________, which is further oxidized by xanthine oxidase to form uric acid.
- Inosine & Guanine
- Hypoxanthine & Guanine
Hyperuricemia is typically asymptomatic and does not lead to _______, but ________ is perceded by hyperuricemia.
Is the vast majority of gout caused by underexcretion or overproduction?
Increased levels of PRPP lead to increases in purine production, causing _________ that can lead to _______.
_________ agents, such as _________ or __________, that increase renal excretion of uric acid, are used in patients who are "underexcretors" of uric acid.
- Probenecid or Sulfinpyrazone
_________, a structural analog of hypoxanthine, inhibits uric acid synthesis and is used in patients who are "overproducers" of uric acid.
What is another non-purine inhibitor of XO?
Allopurinol is converted in the body to oxypurinol, which inhibits ________ _________, resulting in an accumulation of hypoxanthine and xanthine -- compounds that are more soluble than uric acid and, therefore, less likely to initiate an inflammatory response.
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