Question 1

Function of Salvage/Degradation pathways

Accepted Answer

Degradation pathways are designed to
- salvage some nucleotides and 
-to produce uric acid

Question 2

Function of Ribonucleotide reductase

Accepted Answer

Ribonucleotide reductase reduces nucleoside diphosphates (ADP, GDP, CDP, and UDP) to their deoxy forms (e.g., dADP) in a reaction that requires reduced thioredoxin as a cofactor.

Question 3

Cofactor required for ribonucleotide reductase to work

Accepted Answer

Reduced thioredoxin

Question 4

Source of reduced thioredoxin

Accepted Answer

Oxidized thioredoxin is converted into reduced thioredoxin by Thioredoxin reductase

Question 5

Cofactor needed for Thioredoxin reductase to produce reduced thioredoxin

Accepted Answer

NADPH

Question 6

Committed step in de novo purine synthesis

Accepted Answer

Formation of 5-phosphoribosylamine from PRPP

Question 7

1)What prevents overproduction of purines
2) what can overcome the answer to question 1)

Accepted Answer

1)End-product feedback inhibition of this reaction by GMP, AMP and IMP
2) high PRPP concentrations overcome this inhibition.

Question 8

Rate limiting enzyme of de novo purine synthesis

Accepted Answer

Ribose phosphate pyrophosphokinase (PRPP synthetase)

Question 9

An activated form of ribose 5-phosphate is called?

Accepted Answer

PRPP

Question 10

How do you achieve balanced production of AMP and GMP in de novo purine synthesis

Accepted Answer

1)cross-regulation (the end product of one pathway is needed for the other pathway eg. the GMP pathway requires ATP, and the AMP pathway requires GTP)
2) end-product inhibition of each pathway eg. GMP inhibits IMP to GMP rxn when enough GMP has been made

Question 11

Location of CPS I &II

Accepted Answer

CPS I - mitochondrion, in urea synthesis
CPS II - cytosol, pyrimidine synthesis

Question 12

committed step in pyrimidine synthesis, and its regulators

Accepted Answer

Reaction catalyze by CPS II.
Regulators:  - UTP
                     + ATP

Question 13

Function of aspartame  transcarbamoylase

Accepted Answer

Aspartate transcarbamoylase adds aspartate to carbamoyl phosphate, producing carbamoyl aspartate

Question 14

Dihydroorate DNase 
1) aka
2) inhibited by

Accepted Answer

1) dihydroorotase
2) leflunomide

Question 15

Enzyme impaired in orotic aciduria

Accepted Answer

UMP synthase

Question 16

1)Function of thymidylate synthase
2) what does it use as carbon donor

Accepted Answer

1)Thymidylate synthase methylates dUMP to dTMP
 2) using methylene tetrahydrofolate as the carbon donor

Question 17

1)Which pyrimidines are salvaged
2) which pyrimidine is not salvaged
3) what enzyme converts them into nucleotides

Accepted Answer

1) uracil and thymine
2)cytosine 
3)pyrimidine phosphoribosyl transferase

Question 18

Anticancer Drugs Inhibiting Nucleotide Synthesis

Accepted Answer

HYDROXYUREA
MTX
5-FU

Question 19

Hydroxyurea
1)Moa 
2) uses

Accepted Answer

1)Inhibits ribonucleotide reductase, which converts ribonucleotides to deoxyribonucleotides, decreasing deoxyribonucleotides and DNA synthesis
2) CML and sickle cell anemia, in which it increases synthesis of hemoglobin F and decreases sickling

Question 20

MTX
1)moa 
2) uses

Accepted Answer

1)Competitively inhibits dihydrofolate reductase (DHR), which catalyzes reduction of DHF to THF required for synthesis of thymidine and purine nucleotides 
2) Molar disease (hydatidiform moles and choriocarcinoma), leukemias and lymphomas, osteogenic sarc

Question 21

5-FU
1)moa 
2)uses

Accepted Answer

1)Converted by tumor cell enzymes to 5-fluorodeoxyuridine monophosphate (FdUMP), which irreversibly inhibits thymidylate synthase and prevents the synthesis of dTMP from dUMP
2) Breast, stomach, and colon cancers

Question 22

AMP deaminase

Accepted Answer

converts AMP to IMP

Question 23

adenosine deaminase

Accepted Answer

1)Converts adenosine to inosine
2) also, converts 2-deoxyadenosine monophosphate (dAMP) to 2-deoxyinosine monophosphate (dIMP)

Question 24

Deficiency of adenosine deaminase

Accepted Answer

SCID

Question 25

5’-Nucleotidase

Accepted Answer

Converts IMP to inosine, and GMP to guanosine

Question 26

xanthine oxidase

Accepted Answer

1)Converts Guanine and hypoxanthine into xanthine
2) converts xanthine into uric acid

Question 27

Production of uric acid

Accepted Answer

AMP >IMP >inosine >hypoxanthine >xanthine >uric acid

Question 28

Allopurinol

Accepted Answer

Inhibits xanthine oxidase, reducing uric acid

Question 29

Gout

Accepted Answer

Underexcretion (most common) or overproduction of uric acid

Question 30

Adenosine deaminase deficiency

Accepted Answer

(AR); combined B-and T-cell deficiency (SCID); first gene therapy experiment

Question 31

end product of purine degradation

Accepted Answer

Uric acid

Question 32

1)What purines are salvaged
2) what enzymes salvage them

Accepted Answer

1) Guanine and Adenine via hypoxanthine
2) HGPRT and APRT

Question 33

HGPRT  deficiency

Accepted Answer

Leach-nyhan syndrome

Question 34

Pyrimidine  nucleotides  are  degraded  to

Accepted Answer

CO2, NH4+ , and B-amino acids

Question 35

end  product  of  pyrimidine  degradation

Accepted Answer

UREA

(NH4+  is  metabolized  in  the  urea  cycle)

Question 36

SCID

Accepted Answer

deficiency of adenosine deaminase > accumulation of adenosine(toxic to B and T lymphocytes) > also, accumulation of dAMP which is converted to dADP and dATP > dATP inhibits ribonucleotide reductase > decreased DNA synthesis  in  B and T cells > Combined B

Question 37

Causes of gout

Accepted Answer

1)Overproduction of uric  acid (due to overactivity of PRPP synthetase OR deficiency of HGPRT)

2) underexcretion of uric acid by the kidneys

Question 38

Joint most often affected in gout

Accepted Answer

Metatarsophalageal joint of large toe

Question 39

Hallmark of gout

Accepted Answer

hyperuricemia with  deposition of monosodium  urate(MSU) crystals in synovial fluid

Question	Answer
Difference between nucleoside and nucleotide
Function of Salvage/Degradation pathways	Degradation pathways are designed to - salvage some nucleotides and -to produce uric acid
Function of Ribonucleotide reductase	Ribonucleotide reductase reduces nucleoside diphosphates (ADP, GDP, CDP, and UDP) to their deoxy forms (e.g., dADP) in a reaction that requires reduced thioredoxin as a cofactor.
Cofactor required for ribonucleotide reductase to work	Reduced thioredoxin
Source of reduced thioredoxin	Oxidized thioredoxin is converted into reduced thioredoxin by Thioredoxin reductase
Cofactor needed for Thioredoxin reductase to produce reduced thioredoxin	NADPH
Committed step in de novo purine synthesis	Formation of 5-phosphoribosylamine from PRPP
1)What prevents overproduction of purines 2) what can overcome the answer to question 1)	1)End-product feedback inhibition of this reaction by GMP, AMP and IMP 2) high PRPP concentrations overcome this inhibition.
Rate limiting enzyme of de novo purine synthesis	Ribose phosphate pyrophosphokinase (PRPP synthetase)
An activated form of ribose 5-phosphate is called?	PRPP
How do you achieve balanced production of AMP and GMP in de novo purine synthesis	1)cross-regulation (the end product of one pathway is needed for the other pathway eg. the GMP pathway requires ATP, and the AMP pathway requires GTP) 2) end-product inhibition of each pathway eg. GMP inhibits IMP to GMP rxn when enough GMP has been made
Location of CPS I &II	CPS I - mitochondrion, in urea synthesis CPS II - cytosol, pyrimidine synthesis
committed step in pyrimidine synthesis, and its regulators	Reaction catalyze by CPS II. Regulators: - UTP + ATP
Function of aspartame transcarbamoylase	Aspartate transcarbamoylase adds aspartate to carbamoyl phosphate, producing carbamoyl aspartate
Dihydroorate DNase 1) aka 2) inhibited by	1) dihydroorotase 2) leflunomide
Enzyme impaired in orotic aciduria	UMP synthase
1)Function of thymidylate synthase 2) what does it use as carbon donor	1)Thymidylate synthase methylates dUMP to dTMP 2) using methylene tetrahydrofolate as the carbon donor
1)Which pyrimidines are salvaged 2) which pyrimidine is not salvaged 3) what enzyme converts them into nucleotides	1) uracil and thymine 2)cytosine 3)pyrimidine phosphoribosyl transferase
Anticancer Drugs Inhibiting Nucleotide Synthesis	HYDROXYUREA MTX 5-FU
Hydroxyurea 1)Moa 2) uses	1)Inhibits ribonucleotide reductase, which converts ribonucleotides to deoxyribonucleotides, decreasing deoxyribonucleotides and DNA synthesis 2) CML and sickle cell anemia, in which it increases synthesis of hemoglobin F and decreases sickling
MTX 1)moa 2) uses	1)Competitively inhibits dihydrofolate reductase (DHR), which catalyzes reduction of DHF to THF required for synthesis of thymidine and purine nucleotides 2) Molar disease (hydatidiform moles and choriocarcinoma), leukemias and lymphomas, osteogenic sarc
5-FU 1)moa 2)uses	1)Converted by tumor cell enzymes to 5-fluorodeoxyuridine monophosphate (FdUMP), which irreversibly inhibits thymidylate synthase and prevents the synthesis of dTMP from dUMP 2) Breast, stomach, and colon cancers
AMP deaminase	converts AMP to IMP
adenosine deaminase	1)Converts adenosine to inosine 2) also, converts 2-deoxyadenosine monophosphate (dAMP) to 2-deoxyinosine monophosphate (dIMP)
Deficiency of adenosine deaminase	SCID
5’-Nucleotidase	Converts IMP to inosine, and GMP to guanosine
xanthine oxidase	1)Converts Guanine and hypoxanthine into xanthine 2) converts xanthine into uric acid
Production of uric acid	AMP >IMP >inosine >hypoxanthine >xanthine >uric acid
Allopurinol	Inhibits xanthine oxidase, reducing uric acid
Gout	Underexcretion (most common) or overproduction of uric acid
Adenosine deaminase deficiency	(AR); combined B-and T-cell deficiency (SCID); first gene therapy experiment
end product of purine degradation	Uric acid
1)What purines are salvaged 2) what enzymes salvage them	1) Guanine and Adenine via hypoxanthine 2) HGPRT and APRT
HGPRT deficiency	Leach-nyhan syndrome
Pyrimidine nucleotides are degraded to	CO2, NH4+ , and B-amino acids
end product of pyrimidine degradation	UREA (NH4+ is metabolized in the urea cycle)
SCID	deficiency of adenosine deaminase > accumulation of adenosine(toxic to B and T lymphocytes) > also, accumulation of dAMP which is converted to dADP and dATP > dATP inhibits ribonucleotide reductase > decreased DNA synthesis in B and T cells > Combined B
Causes of gout	1)Overproduction of uric acid (due to overactivity of PRPP synthetase OR deficiency of HGPRT) 2) underexcretion of uric acid by the kidneys
Joint most often affected in gout	Metatarsophalageal joint of large toe
Hallmark of gout	hyperuricemia with deposition of monosodium urate(MSU) crystals in synovial fluid

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Nucleotide syn & met