Flashcards in Lecture 39 Deck (27)
What is a nucleoside?
N-containing base and ribose (no P)
what is a nucleotide?
N-containing base, ribose, and phosphate
What is the bond between the base and the ribose?
What are the precursor molecules to make a purine nucleotide?
glutamine, glycine, aspartate and formyl tetrahydrofolate
explain the pentose phosphate pathway?
1. ribose phosphate
2. PRPP synthetase enzyme
3. Phosphoribosyl pyrophosphate (PRPP)
4. Phosphoribosylamidotransferase with glutamate
6. Other C and N atoms are added to make Inosine mono phosphate (IMP)
7. IMP can be converted into either AMP or GMP
What is the regulated enzyme in the pentose phosphate pathway?
What enzyme is the committing step in the pentose phosphate pathway?
Phosphoribosylamidotransferase: Committed step
(Regulated step) – N donated by glutamine
How is IMP converted into ATP
1. requires GTP
2. IMP + GTP will make AMP
3. AMP + kinase = ADP
4. ADP + kinase = ATP
How is IMP converted into GTP
1. requires ATP
2. ATP + GTP = GMP
3. GMP + kinase = GDP
4. GDP + kinase = GTP
How is the production of ATP and GTP managed?
They cross regulate each other with ensures that ATP and GTP are the same concentration in the cell
What inhibits the conversion of IMP to GMP?
What enzyme in the pentose phosphate pathway is a feedforward activator?
high PRPP in the cell leads to increased purine synthesis
How does an abundance of pruine nucleotides impact the pentose phosphate pathway?
abundant purine nucleotides will inhibit the enzymes PRPP and phosphoribosylamidotransferase
How is folate used in purine synthesis? (Humans)
1. must get folate in the diet
2. folic acid is converted to dihydrofolic acid by dihydrofolate reductase
3. dihydrofolic acid is converted to tetrahydrofolic acid by dihydrofolate reductase
4. THF or tetrahydrofolic acid is used for purine synthesis
What drug can be used to inhibit dihydrofolic reducatse?
What can trimethoprim be used for?
How to inhibit bacterial conversion of PABA to folate?
sulfonamide / sulfa drugs
folate analog; competitive inhibitor of dihydrofolate reductase
less purine synthesis
thiopurine and azathioprine
anti cancer drugs
what occurs during folate deficiency?
macrocytic anemia and decreased cell division
can lead to neural tube defects in a fetus
how do ribonucleotides get converted into deoxynucleotides?
ribonucleoside diphosphate is converted to deoxyribonucleoside diphosphate by ribonucleotide reductase
what does the enzyme ribonucleotide reductase need?
thioredoxin and NADPH+H
What can inhibit the conversion of ribo to deoxyribo?
a lot of dATP
what drug can inhibit ribonucleotide reductase?
What are the enzymes of the purine salvage pathway?
HGPRT and APRT
What does the loss of the HGPRT enzyme cause?