Lecture 36 & 37

Question 1

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

Answer 1

• A nucleoside esterified to one or more Phosphate groups.

- nucleoside

Question 2

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

Answer 2

• Ribose-5-Phosphate

- ATP

Question 3

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

Answer 3

• PRPP is utilized in making a purine nucleotide

- Aspartate, Glutamine, Glycine, HCO3-, H4folate

Question 4

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

Answer 4

• The carbon 1 of ribose

- yes - we are building stuff after all

Question 5

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

Answer 5

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

Question 6

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

Answer 6

1. inosine (IMP) > xanthine (XMP) > guanine (GMP)

2. inosine (IMP) > adenylosuccinate > Adenosine (AMP)

Question 7

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

Answer 7

• IMP, GMP, AMP, ADP
• PRPP
• same as above + conc of PRPP
• GMP
• AMP

Question 8

What happens to excess bases in the body?

Answer 8

They are metabolized and excreted from the body

Question 9

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

Answer 9

• They can be directly attached to PRPP to make GMP and AMP

- phosphoribosyl transferases

Question 10

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

Answer 10

• yes

- ammonia (NH4)

Question 11

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

Answer 11

• The base is built and then attached to PRPP

- Glutamine, HCO3-, aspartate (4 carbons!)

Question 12

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

Answer 12

• uracil - uridine 5-mono-phosphate (UMP)

- not until later in comparison to purines

Question 13

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

Answer 13

• yes
• phosphotransferases
• yes

Question 14

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

Answer 14

• CTP synthetase, ATP and glutamine

Question 15

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

Answer 15

• UTP is negative, PRPP and ATP are positive

Question 16

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

Answer 16

• 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

Question 17

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?

Answer 17

• Ribonucleotide Reductase
• accessory protein with 2 sulfhydryl (cysteine) residues
• NADPH

Question 18

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

Answer 18

• phosphotransferase

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

Question 19

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

Answer 19

NAD, FAD, Coenzyme A

Question 20

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?

Answer 20

• 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

Question 21

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

Answer 21

• uric acid

- must be further metabolized or directly excreted

Question 22

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

Answer 22

• 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)

Question 23

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

Answer 23

• primates

- uric acid has anti-oxidant properties

Question 24

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

Answer 24

• as a solid

- ammonia

Question 25

Do some species further degrade allantoin?

Answer 25

yes

Question 26

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?

Answer 26

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

Question 27

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

Answer 27

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

Question 28

Explain inhibitors of nucleotide metabolism as pharmacologic agents

Answer 28

- 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