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M1 > Purine and Pyrimidine Breakdown and Heme > Flashcards

Purine and Pyrimidine Breakdown and Heme Flashcards

1
Q

Ribonucleotides are the Precursors
of

A

Deoxyribonucleotides

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2
Q

converts ribonucleotides to deoxyribonucleotides

A

ribonucleotide reductase

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3
Q

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

A

thioredoxin

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4
Q

catalyzes the reduction of the oxidized form of thioredoxin by NADPH

A

thioredoxin reductase

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5
Q

transfers reducing power from glutathione (GSH) to ribonucleotide reductase

A

glutaredoxin

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6
Q

electrons are transmitted to the enzyme from NADPH via

A

glutaredoxin or thioredoxin

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7
Q

Regulation of E. coli
Ribonucleotide Reductase

Each α subunit has two types of regulatory sites:

A
  • 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
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8
Q

Regulation of Ribonucleotide Reductase by Deoxynucleoside Triphosphates

A

provides a balanced pool of precursors for DNA synthesis

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9
Q
A
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10
Q

Thymidylate is derived from:

A

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
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11
Q
A
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12
Q

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

A

thymidylate synthase

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13
Q

reduces dihydrofolate to tetrahydrofolate

A

dihydrofolate reductase

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14
Q
A
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15
Q

Folic Acid Deficiency Leads to

A

Reduced thymidylate synthesis

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16
Q

folic acid deficiency occurs in __________ of the human population

and up to ________ of people in impoverished communities

A

10%; 50%

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17
Q

reduced thymidylate synthesis cause ______to be incorporated into DNA

A

uracil

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18
Q

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

A

cancer, heart disease, and neurological impairment

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19
Q

Degradation of Purines and Pyrimidines produces:

A

Uric acid and urea respectively

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20
Q

removes the phosphate from purine nucleotides

adenylate yields adenosine

A

5’-nucleotidase

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21
Q

deaminates adenosine to inosine

A

adenosine deaminase

22
Q

inosine is hydrolyzed to:

oxidized to:

A

hypoxanthine

xanthine

23
Q
A
24
Q

GMP Catabolism

A
  • GMP is first hydrolyzed to guanosine, which is then cleaved to free guanine
  • guanine undergoes hydrolytic removal of its amino group to yield xanthine
25
Q
A
26
Q

flavoenzyme that catalyzes the oxidation of xanthine to uric acid

A

xanthine oxidase

contains an atom of molybdenum and four iron-sulfur centers in its prosthetic group

molecular oxygen is the electron acceptor

27
Q
A
28
Q

Catabolism of Purnine Nucleotides

A
29
Q

Catabolism of Pyrimidines:

A
  • 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
30
Q

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

A

adenosine deaminase (ADA) deficiency

31
Q

free purines can be salvaged and rebuilt into

A

nucleotides

32
Q

catalyzes the reaction of a free adenine with PRPP to yield the corresponding adenine nucleotide

adenine + PRPP → AMP + PPi

A

adenosine phosphoribosyl-transferase

33
Q

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

A

hypoxanthine-guanine phosphoribosyltransferase

34
Q

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

A

Lesch-Nyhan syndrome

35
Q
  • 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
A

gout

36
Q

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

A

allopurinol

37
Q

at the active site, allopurinol is converted to

A

oxypurinol, a strong competitive inhibitor

remains tighlty bound to the enzyme

38
Q

Many chemotherapies agents target enzymes in

specific targets include:

A

Nucleotide Biosynthetic Pathways

thymidylate synthase and dihydrofolate reductase, enzymes that provide the only cellular pathway for thymine synthesis

39
Q

Thymidylate Synthesis and Folate Metabolism

A
40
Q

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

A

fluorouracil

41
Q

FdUMP binds and inactivates

A

thymidylate synthase

42
Q
  • 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
A

methotrexate

43
Q
  • 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
A

trimethoprim

44
Q

Glycine is a precursor to______

constructed from four molecules of the monopyrrole derivative porphobilinogen (derived from two molecules of δ-aminolevulinate)

A

porphyrins

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

45
Q

Biosynthesis of δ-Aminolevulinate in Higher Eukaryotes

A

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

46
Q

Two Major Pathways to δ-aminolevulinate

A
47
Q

Biosynthesis of Protoporphyrin

A
  • 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
48
Q

Biosynthesis of Heme From δ-aminolevulinate

A
49
Q

Heme Degradation Has Multiple Functions

A
  • degradation of iron-porphyrin (heme) generates bilirubin, which is converted to bile pigments
  • breakdown pathways protect cells from oxidative damage
50
Q

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

A

three

51
Q

expression of HO-1 is induced by stress conditions:

A
  • shear stress
  • uncontrolled angiogenesis (development of blood vessels)
  • hypoxia and hyperoxia
  • heat shock
  • ultraviolet light
  • hydrogen peroxide
52
Q
  • 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 _________.
A

brain and testes

is not; oxygen sensing

M1 (48 decks)

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