Nucleic Acid Metabolism

Question 1

functions of nucleotides

Answer 1

-building molecules for DNA and RNA
-energy shuttles
-cofactor components
-activation of biosynthetic intermediates
-second messengers

Question 2

glutamine’s role in nucleotide synthesis

Answer 2

major provider of amino groups

Question 3

glycine plays a large role in (purine/pyrimidine) synthesis

Answer 3

PURINE

Question 4

aspartate plays a large role in (purine/pyrimidine) synthesis

Answer 4

PYRIMIDINE

Question 5

rate-limiting enzyme for purine nucleotide de novo synthesis

Answer 5

glutamine PRPP aminotransferase

Question 6

glutamine PRPP aminotransferase

Answer 6

catalyzes the first committed step in PURINE DE NOVO SYNTHESIS; takes the ammonia from glutamine and adds it as an amino group on ribose sugar

Question 7

purine metabolism

Answer 7

1. imidazole ring formation
2. glycine and glutamine provide most of the carbon and nitrogen
3. tetrahydrofolate donates carbon atoms one at a time (so folate is important)
4. ATP used for energetics
5. aspartate and glutamine donate the exocyclic amino group to make AMP and GMP, respectively

Question 8

regulation of purine nucleotide synthesis

Answer 8

-high levels of AMP inhibit conversion of IMP to AMP
-high levels of GMP inhibit conversion of IMP to GMP

Question 9

catabolism of purine nucleotides yields

Answer 9

uric acid

Question 10

catabolism of AMP - steps

Answer 10

1) amino group removed to produce inosine
2) nucleosidase releases hypoxanthine
3) hypoxanthine is oxidized by xanthine oxidase to xanthine
4) xanthine is oxidized to uric acid

Question 11

catabolism of GMP

Answer 11

1) GMP is converted to guanosine by removal of phosphate
2) nucleosidase releases free base, guanine
3) guanine is deaminated to form xanthine
4) xanthine is oxidized to form uric acid

Question 12

purine ring salvage pathways

Answer 12

a shortcut whereby purines liberated during normal nucleic acid turnover can be converted to nucleosides and their triphosphates
*important enzyme = HGPRT (hypoxanthine:guanine phosphoribosyltransferase)
*deficiency= Lesch-Nyhan syndrome

Question 13

important enzyme for purine ring salvage pathways

Answer 13

hypoxanthine:guanine phosporibosyltransferase (HGPRT)

Question 14

hypoxanthine:guanine phosporibosyltransferase

Answer 14

takes hypoxanthine or guanine and attaches it to PRPP to form salvaged purines

Question 15

how does allopurinol treat gout

Answer 15

*MOA: inhibits xanthine oxidase
-excreted products are xanthine and hypoxanthine (instead of uric acid), which are more water soluble and less likely to form crystals than uric acid

Question 16

Von Gierke disease

Answer 16

*defect in glucose-6-phosphatase causes buildup of glucose-6-phosphate, which gets shunted toward pentose phosphate pathway, leading to excess uric acid and gout
*inability to get glucose OUT of the liver

Question 17

Lesch-Nyhan syndrome

Answer 17

*deficiency of hypoxanthine-guanine phosphoribosyltransferase activity [HGPRT] (the enzyme important in purine salvage pathway), leading to increased de novo purine synthesis and therefore increased uric acid because there is more purine nucleotide to degrade

Question 18

tumor lysis syndrome

Answer 18

large amounts of cellular DNA occur when tumor cells are lysed (can be due to chemotherapy or spontaneous tumor lysis), and degradation of the purines leads to increased uric acid, which could clog the kidneys

Question 19

rate-limiting enzyme in de novo pyrimidine synthesis

Answer 19

1) carbamoyl phosphate synthetase II (CPS-II); resides in cytosol (stage 1)
2) aspartate transcarbamoylase (stage 2)
3) stage 3 yields UTP and CTP

Question 20

thymidylate synthase

Answer 20

transfers a methyl group to dUMP to make dTMP; requires activated vitamin B9 (tetrahydrofolate)

Question 21

ribonucleotide reductase

Answer 21

converts ribonucleotides to deoxyribonucleotides

note - inhibited by hydroxyurea

Question 22

dihydrofolate reductase

Answer 22

needed to make tetrahydrofolate in dTMP synthesis

Question 23

chemotherapy involving ribonucleotide reductase

Answer 23

chemo inhibits the ribonucleotide reductase in order to prevent deoxyribonucleotides from forming, so rapidly dividing cells cannot undergo DNA replication and therefore cannot divide

Question 24

chemotherapy involving dihydrofolate reductase

Answer 24

1) trimethoprim - binds to BACTERIAL dihydrofolate reductase, so they can’t reduce dihydrofolate to tetrahydrofolate and therefore dTMP synthesis cannot occur, stopping DNA synthesis & cell division

2) methotrexate - structural analog of THF, so it competitively inhibits dihydrofolate reductase and therefore dTMP synthesis cannot occur, stopping DNA synthesis & cell division

Question 25

amino acid precursors to carnitine

Answer 25

lysine residues from proteins
*requires vitamin C

Question 26

function of carnitine

Answer 26

mediates fatty acid entry into the mitochondrion via the carnitine shuttle

Question 27

amino acid precursors to creatine

Answer 27

methionine, glycine, and arginine

Question 28

function of creatine

Answer 28

serves as a high energy phosphate donor to allow for storage of energy that is crucial for muscle cells to function

Question 29

catecholamine neurotransmitters

Answer 29

epinephrine, norepinephrine, and dopamine

Question 30

amino acid precursors for catecholamine neurotransmitters

Answer 30

phenylalanine and tyrosine

Question 31

phenylketonuria biochemistry

Answer 31

defective phenylalanine hydroxylase, so you can’t convert phenylalanine to tyrosine; causes tyrosine deficiency and excess phenylalanine

Question 32

clinical features of phenylketonuria

Answer 32

-generalized hypopigmentation of hair, skin, and eyes
-urine has a classic “mousy” odor
-causes CNS damage
-self-mutilation