Lecture 36 & 37 Flashcards Preview

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Flashcards in Lecture 36 & 37 Deck (28):

What is a nucleotide? What is it called if no phosphates are attached?

- A nucleoside esterified to one or more Phosphate groups.
- nucleoside


5-Phosphoribosyl-1-pyrophosphate (PRPP) is made from what using what?

- Ribose-5-Phosphate


What is utilized in making a purine nucleotide? What make up its parts?

- PRPP is utilized in making a purine nucleotide
- Aspartate, Glutamine, Glycine, HCO3-, H4folate


In synthesis of purine utilizing PRPP - where is the stuff being stuck onto? Is energy required to make purines?

- The carbon 1 of ribose
- yes - we are building stuff after all


What is produced at the end of purine synthesis? What is the importance of this compound (the first part)?

- Inosine-5-monophosphate (IMP)
- (inosine) exists at relatively high concentrations in cells, key intermediate in biosynthesis, and degradation of nucleotides


What can be made from inosine (IMP) and by what are the intermediates?

1. inosine (IMP) > xanthine (XMP) > guanine (GMP)
2. inosine (IMP) > adenylosuccinate > Adenosine (AMP)


What inhibits the initial use of PRPP? activates? What inhibits second step (PGAT)? What inhibits IMP > XMP? What inhibits IMP > adenylosuccinate?

- same as above + conc of PRPP


What happens to excess bases in the body?

They are metabolized and excreted from the body


If there are already adenine or guanine (purine) bases floating around in sufficient quantities what can be done with them? What performs this reaction?

- They can be directly attached to PRPP to make GMP and AMP
- phosphoribosyl transferases


Can you convert GMP and AMP to IMP? If so, what is released in each of these reactions?

- yes
- ammonia (NH4)


What is different about pyrimidine synthesis vs. purine? What is pyrimidine built from?

- The base is built and then attached to PRPP
- Glutamine, HCO3-, aspartate (4 carbons!)


After 6 steps in pyrimidine nucleotide synthesis what is made? When does PRPP come in?

- uracil - uridine 5-mono-phosphate (UMP)
- not until later in comparison to purines


Can you make UTP from UMP? Using what enzyme? Is this true for other nucleotides?

- yes
- phosphotransferases
- yes


What is used (enzyme and substrates) in the conversion of CTP (cytosine) from UTP?

- CTP synthetase, ATP and glutamine


What are the allosteric feedback regulators of the first step of pyrimidine biosynthesis?

- UTP is negative, PRPP and ATP are positive


What is DUMPS? What does it affect? What does this enzyme do? What does this lead to? What does that lead to?

- Deficiency of Uridine Monophosphate Synthase
- Cattle (Holstein again)
- Bifunctional enzyme that performs the last 2 steps of UMP formation
- Increased serum levels of orotic acid
- Deceased levels of nucleotides for rapidly dividing cells


What enzyme is utilized in the synthesis of 2-deoxyribonucleotides (dNDP) from ribonucleotides (NDP)? What is the accessory protein used? What is used to break the resulting disulfide bridge?

- Ribonucleotide Reductase
- accessory protein with 2 sulfhydryl (cysteine) residues


What converts dADP to dATP for example? What can dTTP be made from?

- phosphotransferase
- dCDP or UDP (dUDP) - these two meet at dUMP


What can be made from De Novo synthesis of "other" nucleotides?

NAD, FAD, Coenzyme A


When nucleic acids are subjected to nucleases - what are created? Once those are created and are subjected to nucleotidases - what is created? After this, then what does the phosphorylase produce? What is made from these bases and what does this turn into? What enzyme does this reaction? What is given off in the xanthine oxidase reaction? Where is this enzyme present?

- Guanine and Adenine nucleotides
- nucleosides (guanosine and inosine (after some other stuff)
- bases (guanine and hypoxanthine) and ribose-1-Phos
- Xanthine, uric acid
- xanthine oxidase
- H2O2
- in many tissues and cells, including the gut


What is the end product of purine degradation in all species? What must be done with it?

- uric acid
- must be further metabolized or directly excreted


What is the problem with uric acid? How do most mammals deal with this?

- not very soluble in water and can precipitate in fluids
- most mammals, using uricase in their livers, convert uric acid to allantoin for excretion by liver (more soluble than uric acid)


Which mammals have lost a functional uricase gene? What could be an advantage of this?

- primates
- uric acid has anti-oxidant properties


How do birds and reptiles directly excrete uric acid? What is also excreted this way by being converted to uric acid?

- as a solid
- ammonia


Do some species further degrade allantoin?



Which animal has a defect in allantoin production? What is it called? What is the cause? What is caused by it? What is a possible solution? Is it a perfect solution?

- Dalmations
- hyperuricosemia
- mutation in urate transporter
- stones
- Use of allopurinol, a xanthine oxidase inhibitor, slows uric acid production
- no


What occurs in degradation of pyrimidine nucleotides? What allows them to be more soluble? What is the ultimate product and how is it excreted?

- crack open ring structure
- COO and H2N groups
- ammonia - urea cycle


Explain inhibitors of nucleotide metabolism as pharmacologic agents

- structural analogues of natural substrates of enzymes of nucleotide metabolism
- disrupt DNA and RNA synthesis (hopefully more in tumor or pathogen than normal cell)
- example... AZT