Purine and Pyrimidine Breakdown and Heme

Question 1

Ribonucleotides are the Precursors
of

Answer 1

Deoxyribonucleotides

Question 2

converts ribonucleotides to deoxyribonucleotides

Answer 2

ribonucleotide reductase

Question 3

intermediate hydrogen-carrying protein that carries a pair of hydrogen atoms from NADPH to the ribonucleoside diphosphate

has pairs of –SH groups that carry hydrogen atoms

Answer 3

thioredoxin

Question 4

catalyzes the reduction of the oxidized form of thioredoxin by NADPH

Answer 4

thioredoxin reductase

Question 5

transfers reducing power from glutathione (GSH) to ribonucleotide reductase

Answer 5

glutaredoxin

Question 6

electrons are transmitted to the enzyme from NADPH via

Answer 6

glutaredoxin or thioredoxin

Question 7

Regulation of E. coli
Ribonucleotide Reductase

Each α subunit has two types of regulatory sites:

Answer 7

• one type affects overall enzyme activity
  
  • ATP activates the enzyme
  • dATP inactivates the enzyme
• one type alters substrate specificity in response to the effector molecule that is bound
  
  • ATP or dATP favors reduction of UDP and CDP
  • dTTP favors reduction of GDP
  • dGTP favors reduction of ADP

Question 8

Regulation of Ribonucleotide Reductase by Deoxynucleoside Triphosphates

Answer 8

provides a balanced pool of precursors for DNA synthesis

Question 9

Answer 9

Question 10

Thymidylate is derived from:

Answer 10

dCDP and dUDP

• the immediate precursor of thymidylate (dTMP) is dUMP
• in bacteria, a dUTPase converts dUTP to dUMP
• dUTP forms by deamination of dCTP or by phosphorylation of dUDP

Question 11

Answer 11

Question 12

catalyzes the conversion of dUMP to dTMP

a one-carbon unit is transferred from N5,N10-methylenetetrahydrofolate to dUMP, then reduced to a methyl group

Answer 12

thymidylate synthase

Question 13

reduces dihydrofolate to tetrahydrofolate

Answer 13

dihydrofolate reductase

Question 14

Answer 14

Question 15

Folic Acid Deficiency Leads to

Answer 15

Reduced thymidylate synthesis

Question 16

folic acid deficiency occurs in __________ of the human population

and up to ________ of people in impoverished communities

Answer 16

10%; 50%

Question 17

reduced thymidylate synthesis cause ______to be incorporated into DNA

Answer 17

uracil

Question 18

repair mechanisms remove the uracil by creating strand breaks that affect the structure and function of DNA and is associated with:

Answer 18

cancer, heart disease, and neurological impairment

Question 19

Degradation of Purines and Pyrimidines produces:

Answer 19

Uric acid and urea respectively

Question 20

removes the phosphate from purine nucleotides

adenylate yields adenosine

Answer 20

5’-nucleotidase

Question 21

deaminates adenosine to inosine

Answer 21

adenosine deaminase

Question 22

inosine is hydrolyzed to:

oxidized to:

Answer 22

hypoxanthine

xanthine

Question 23

Answer 23

Question 24

GMP Catabolism

Answer 24

• GMP is first hydrolyzed to guanosine, which is then cleaved to free guanine
• guanine undergoes hydrolytic removal of its amino group to yield xanthine

Question 25

Answer 25

Question 26

flavoenzyme that catalyzes the oxidation of xanthine to uric acid

Answer 26

xanthine oxidase ## Footnote contains an atom of molybdenum and four iron-sulfur centers in its prosthetic group molecular oxygen is the electron acceptor

Question 27

Answer 27

Question 28

Catabolism of Purnine Nucleotides

Answer 28

Question 29

Catabolism of Pyrimidines:

Answer 29

* pathways for degradation lead to NH4+ production and thus to urea synthesis * carbons of thymine are degraded to succinyl-CoA * carbons of cytosine and uracil are degraded to acetyl-CoA

Question 30

leads to a 100-fold increase in [dATP], a strong inhibitor of ribonucleotide reductase causes severe immunodeficiency disease in which T lymphocytes and B lymphocytes do not develop properly produces a general deficiency of other dNTPs in T lymphocytes

Answer 30

adenosine deaminase (ADA) deficiency

Question 31

free purines can be salvaged and rebuilt into

Answer 31

nucleotides

Question 32

catalyzes the reaction of a free adenine with PRPP to yield the corresponding adenine nucleotide adenine + PRPP → AMP + PPi

Answer 32

adenosine phosphoribosyl-transferase

Question 33

catalyzes the salvage of free guanine and hypoxanthine (the deamination product of adenine)

Answer 33

hypoxanthine-guanine phosphoribosyltransferase

Question 34

set of symptoms characterized by poor coordination, intellectual deficits, hostility, and compulsive self-destructive tendencies caused by a genetic lack of hypoxanthine-guanine phosphoribosyltransferase activity

Answer 34

Lesch-Nyhan syndrome

Question 35

* a disease of the joints caused by an elevated concentration of uric acid in the blood and tissues * often involves an underexcretion of urate * genetic deficiency of one or another enzyme of purine metabolism may also be a factor

Answer 35

gout

Question 36

inhibitor of xanthine oxidase that is used in the treatment of gout

Answer 36

allopurinol

Question 37

at the active site, allopurinol is converted to

Answer 37

oxypurinol, a strong competitive inhibitor remains tighlty bound to the enzyme

Question 38

Many chemotherapies agents target enzymes in specific targets include:

Answer 38

Nucleotide Biosynthetic Pathways ## Footnote thymidylate synthase and dihydrofolate reductase, enzymes that provide the only cellular pathway for thymine synthesis

Question 39

Thymidylate Synthesis and Folate Metabolism

Answer 39

Question 40

agent that is converted to the deoxynucleoside monophosphate FdUMP in salvage pathways

Answer 40

fluorouracil

Question 41

FdUMP binds and inactivates

Answer 41

thymidylate synthase

Question 42

* a folate analog that acts as a competitive inhibitor of dihydrofolate reductase * used as a chemotherapeutic agent * aminopterin is a related compound that acts similarly

Answer 42

methotrexate

Question 43

* an antibiotic that binds to bacterial dihydrofolate reductase nearly 100,000 times better than to the mammalian enzyme * treats certain urinary and middle-ear bacterial infections

Answer 43

trimethoprim

Question 44

Glycine is a precursor to\_\_\_\_\_\_ constructed from four molecules of the monopyrrole derivative porphobilinogen (derived from two molecules of δ-aminolevulinate)

Answer 44

porphyrins ## Footnote make up the porphyrin nucleus in heme proteins Porphyrin synthesis id feedback inhibited by heme which is the end-product of the heme synthesis pathway

Question 45

Biosynthesis of δ-Aminolevulinate in Higher Eukaryotes

Answer 45

glycine reacts with succinyl-CoA in the first step to yield α-amino-β-ketoadipate, which is then decarboxylated to δ-aminolevulinate

Question 46

Two Major Pathways to δ-aminolevulinate

Answer 46

Question 47

Biosynthesis of Protoporphyrin

Answer 47

* **porphobilinogen** = formed from two molecules of δ-aminolevulinate * **protoporphyrin** = formed from four molecules of porphobilinogen * iron is incorporated after assembly * **porphyrias** = human diseases caused by genetic defects in the biosynthesis of porphyrins * leads to the accumulation of pathway intermediates

Question 48

Biosynthesis of Heme From δ-aminolevulinate

Answer 48

Question 49

Heme Degradation Has Multiple Functions

Answer 49

* degradation of iron-porphyrin (heme) generates bilirubin, which is converted to bile pigments * breakdown pathways protect cells from oxidative damage

Question 50

humans have at least _______ isozymes of heme oxygenase (HO)

Answer 50

three

Question 51

expression of HO-1 is induced by stress conditions:

Answer 51

* shear stress * uncontrolled angiogenesis (development of blood vessels) * hypoxia and hyperoxia * heat shock * ultraviolet light * hydrogen peroxide

Question 52

* expression of HO-2 is found in ________ where it is continually expressed * HO-3 [is/is not] catalytically active…, but may play a role in \_\_\_\_\_\_\_\_\_.

Answer 52

brain and testes is not; oxygen sensing