Term
| Where does the first step of purine de novo nucleotide synthesis occur and where is the ribose 5-phosphate derived from? |
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Definition
| this step occurs in the cytsol of the liver and the r5P comes from the pentose phosphate pathway when the demand for pentose is greater than the need for NADPH |
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Term
| What are the 2 names for the enzyme that catalyzes the conversion of R5P to PRPP |
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Definition
| PRPP Synthetase or Ribose Phosphate Pyrophosphokinase |
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Term
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Definition
* enzyme also called ATP phosphoribosyl transferase
this is the rate limiting step
* activated by Pi
* inhibited by purine nucleoside di- or triphosphates
* product PRPP also participates in pyrimidine
synthesis, salvage pathways and the formation of
NAD and NADP. |
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Term
| What is the name of the enzyme that catalyzes the committed step of de novo purine synthesis? |
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Definition
| Glutamine-PRPP Amidotransferase (also known as Amidophosphoribosyl Transferase |
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Term
| Describe Glutamine PRPP amidotransferase |
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Definition
catalyses the commited step of de novo purine synthesis
controlled by feedback inhibition
* small active molecules aggregate to larger inactive
molecules
* very high concentrations of PRPP overcome the
nucleotide feedback inhibition |
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Term
| The enzyme that catalyzes the reaction that forms IMP |
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Definition
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Term
| How many ATP are used during de novo purine synthesis and what reactions are the providing energy for? |
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Definition
| 4 ATP are used/ condensation and synthetase reactions both are endothermic. |
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Term
| Name what contributes the different elements of a purine ring |
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Definition
N1: Aspartate
N3, N9: Glutamine
C6: CO2 C2, C8: Formyl-THF
C4, C5, N7: Glycine |
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Term
| WHat types of drugs are inhibitors of prine synthesis and what do they inhibit |
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Definition
| antibiotics and anticancer drugs/ they interfere with the utilization of glutamine and THF |
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Term
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Definition
dereivative of folic acid that is a coenzyme on the transfer od single carbon groups. plays a role in purine and pyrimidine pathways and AA conversions
When defienct actively dividing cells are affected first. |
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Term
|
Definition
a glutamine antagonist that inhibits the steps where glutamine donates a nitrogen (N3 and N9 of the purine ring)
It looks very similar to the glutamine |
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Term
| Methotrexate and folic acid analogues |
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Definition
inhibit the reduction of dihdydrofolate to THF
This lowers the amount of THF available for use in purine synthesis |
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Term
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Definition
Base = Hypoxanthine; Nucleoside = Inosine; Nucleotide = Inosinate
does not accumulate in the cell because it is used to make AMP and GMP
Inhibited by the products(ADP and GDP)
Conversion of IMP to ATP requires GTP and the conversion of IMP to GTP requires ATP |
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Term
| WHat phosphorylates monophospates to become diphosphates? |
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Definition
| base specific nucleotide monophosphate kinases (example guanylate kinase) |
|
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Term
| What is phosphorylates diphosphate nucleotides? |
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Definition
nucleotide diphosphate kinases have a broad specificity can convert any NDP to NTP.
ATP is the general source of transferred phosphate |
|
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Term
| what are the 2 enzymes of the purine salvage pathway? |
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Definition
1. Adenine Phosphoribosyl Transferase (APRT)
2. Hypo-xanthine-guanine Phosphoribosyl Transferase (HGPRT)
They catalyze irreversible reactions |
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Term
| HGPRT deficiency lead to what syndrome |
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Definition
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Term
|
Definition
very active in the liver and muscle
helps to maintain an equilibrium among AMP, ADP, ATP
there is a high turnover rate of ATP in those tissues |
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Term
| Examples of reactions that are catalyzed by HGPRT |
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Definition
Guanine + PRPP-->GMP + PPi
Hypoxanthine + PRPP-->IMP + PPi |
|
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Term
| Examples of reactions cataylzed by APRT |
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Definition
| Adenine + PRPP-->AMP + PPi |
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Term
| Symptoms of Leesh-Nyhan Syndrome |
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Definition
* Inherited deficiency in HGPRT
* Recessive X-linked disorder
that occurs primarily in males
* Increased PRPP and de novo purine synthesis but not enough to compensate
* Characterized by:
Excessive uric acid production
Involuntary Movements
Neurological defects
Mental Retardation
Self Mutilation
Hyperuricemia |
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Term
| Describe Purine degradation |
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Definition
Nucleotidases and nucleosidases release the ribose and phosphates to leave free bases
Uric acid is produced and excreted in the urine.
Other mammals oxidize uric acid further to allantoin, urea and/or ammonia |
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Term
| WHat the the last base formed which is the precursor for uric acid synthesis? |
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Definition
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Term
| What are some treatments for gout? |
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Definition
1. Anti-inflammatory drugs: alleviate pain (ex. colchicine)
2. Uricosuric agents: increase renal excretion of uric acid
(ex. probenecide)
3. Inhibition of xanthine oxidase: decrease formation of
uric acid (ex. allopurinol)
4. Changes in diet: low protein diet; excess of amino
acids increases de novo purine synthesis |
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Term
| a dysfunction in xanthine oxidase causes |
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Definition
|
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Term
| a dysfunction in adenosine deaminase causes what |
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Definition
| severe combined immunodeficiency |
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Term
| What are the sources of the carbon and nitrogen atoms in the pyrimidines? |
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Definition
| glutamine, CO2, and aspartic acid |
|
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Term
| What is the first pyrimidine formed during biosynthesis |
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Definition
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Term
| How is ortotic aciduria treated? |
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Definition
|
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Term
| What enzymes are defective in ortotic aciduria? |
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Definition
inherited deficiency of the bifunctional
enzyme composed of orotate phosphoribosyltransferase
and orotidylate decarboxylase (the last two steps |
|
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Term
| What are some of the signs of ortotic aciduria? |
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Definition
Deficiency results in orotic acid in the blood and urine
* Growth retardation, megaloblastic anemia and leukopenia
are clinical signs of the disease
* Mild forms of the disease lead to an accumulation of
carbamoyl phosphate in the liver mitochondria |
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Term
| How does UMP cure orotic aciduria |
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Definition
Restore depleted UMP levels
UMP gets converted to UTP
CPS II is inhibited by feedback inhibition from UTP |
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Term
| What is a coenzyme ribonucleotide reductase (RR) and what delivers reducing equivalents? |
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Definition
|
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Term
| Describe ribonucleotide reductase |
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Definition
Ribonucleotide Reductase (RR) converts NDPs to dNDPs, which are necessary for DNA synthesis to occur.
* RR is a highly regulated, multisubunit enzyme that is specific for the reduction of NDPs to their deoxy-forms.
* RR is controlled by feedback inhibition, which ensures
balanced production of all four dNTPs. |
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Term
|
Definition
Active Site (R1): ATP activates RR, while dATP binding to the
active site inhibits the overall catalytic activity and prevents
the reduction of any of the four nucleoside diphosphates.
* Substrate Specificity Site (R2): binding of certain nucleoside
triphosphates (ATP, dATP, dTTP or dGTP) to this site
regulates substrate specificity, causing an increase in the
conversion of different species of ribonucleotides as they
are required for DNA synthesis |
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Term
| What does the active site of RR contain? |
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Definition
| the R1 dimer contains 3 cysSH and the substrate is stabilized by a glutamic acid residue |
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Term
| What does the R2 dimer of RR contain? |
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Definition
| tyrosine, which forms a tyrosyl radical (TyrO●). This generates a reactive – cysS ● radical |
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Term
| What type of regulatory sites found on the R1 of RR |
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Definition
THe R1 has active and allosteric sites
ATP enhances reduction; dATP inhibits reduction |
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Term
| What is the sorce of the methyl group for conversion of dUMP to TMP. |
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Definition
THF is the source of the methyl group
THF contributes a carbon and 2 hydrogens.
forming DHF |
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Term
| WHat drug inhibits thymidylate synthase and is widely used a chemotherapy drug. |
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Definition
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Term
| What drugs competitavely inhibit dihydrofolate reductase and lower the supply of THF. Also becasue of this purine synthesis and dTMP production is inhibitd. Inhibits DNA syntheis and replication |
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Definition
| Methotrexate and aminopterin |
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