Nucleotide Sythesis

Question 1

Nucleoside

Answer 1

5 carbon sugar (ribose) + base (PURINE or PYRIMIDINE)

Question 2

Nucleotide

Answer 2

5 carbon sugar (ribose) + base (PURINE or PYRIMIDINE + one or more phosphate

Question 3

Purine Bases

Answer 3

Adenine
Guanine
Hypoxanthine

Question 4

Pyrimidine Bases

Answer 4

Cytosine
Uracil
Thymine

Question 5

What does PPP produce?

Answer 5

Ribose 5 Phosphate and NADPH

Question 6

Roles of nucleotides

Answer 6

Data storage
Energy currency
Cellular communications
Cosubstrates for enzymes
Component of cofactors

Question 7

Nucleosides: Biological Role?

Answer 7

Nucleoside ANALOGS serve as antiviral or anti cancer agents
HOW?
- they cross plasma membrane due to solubility
- cells are tricked into being phosphorylated and becoming nucleotides
- they then inter grate into DNA
But DNA ploymerase recognizes them as foreign and stops replication

Question 8

Purine Biosythesis: What is the first key step?

Answer 8

The conversion of RIBOSE-5-PHOPHATE into PRPP via PRPP SYNTHETASE ATP converted to ADP in the process)
- WE HAVE NOW ACTIVATED OUR SUGAR

Question 9

Purine Biosynthesis: next key step?

Answer 9

PRPP —> PRR
Then, 9 steps (“hand waving”) to get to IMP
—> we incorporate carbons from: CO2, GLYCINE, GLUTAMINE, ASPARTATE, AND N10-fTHF
—> we now convert from IMP to AMP or GMP and these eventually make dATP and dGTP for DNA synthesis!

Question 10

Methotrexate: how does it work?

Answer 10

Our body usually converts the inactive form of folate (dihydroxyfolate) into active form called TETRAHYDROXYFOLAE (which is one of the things needed to convert PRA into IMP)

• However, this drug is a ANALOG of DIHYDROXYFOLATE
• so, it binds to DIHYDROXYFOLATE REDUCTASE 100 TIMES more tightly and prevents conversion to the TETRAHYDROXYFOLATE
• so, TETRAHYDROXYFOLATE is NOT incorporated into the purine pathway
• we won’t make any IMP
• and thus, without IMP, we won’t make any dAMP or dGMP (for DNA synthesis)

Question 11

PYRIMIDINE Synthesis: WHAT ARE THE KEY STEPS?

Answer 11

1. Forming CARBAMOYL PHOSPHATE from BICARBONATE, NH3, and 2 ATPs
   (enzyme: CARBAMOYL PHOSPHATE SYNTHETASE II)

Step 2: After a few steps, you form OROTATE, which is incorporated with PRPP and converted to UMP

(enzyme: UMP synthase)

Step 3: UMP is converted, eventually to UTP and dTTP (which is a necessary nucleotide in DNA synthesis)

Question 12

What is OROTIC ACIDURIA?

Answer 12

This occurs when OROTIC ACID cannot be converted to UMP due to problems with UMP SYHTHASE. So, OROTIC acid accumulates.

Question 13

What is the general name for an enzyme that converts RIBONUCLEOTIDES to DEOXYRIBONUCLEOTIDES?

Answer 13

RIBONUCLEOTIDE REDUCTASE

Question 14

What are the two major control points of PYRIMIDINE Biosythesis?

Answer 14

1. CARBAMOYL PHOSPHATE SYNTHETASE is inhibited by UMP (a downstream product) and by purines. It is stimulated by PRPP.
2. ASPARTATE TRANSCARAMOYLASE is feedback inhibited by CTP

Question 15

Immunosuppressant Drugs (MYCOPHENOLIC ACID)

Answer 15

• they target IMP DEHYDROGENASE (converts IMP to XMP) –> which then goes on to form GMP —-> dGTP
• IMP DEHYDROGENASE is inhibited, which then causes disruption of GTP synthesis, which is needed for dGTP synthesis and encetually DNA replication
• since it effects B and T cells of immune system, IMP dehydrogenase inhibition can be used to suppress immune response to prevent graft rejection