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Biochem Exam 3 > 30 - Nucleotide Metabolism > Flashcards

30 - Nucleotide Metabolism Flashcards

1
Q

This is the term for a nitrogenous base covalently attached to a sugar.

A

Nucleoside

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2
Q

This is the term for a nitrogenous base, sugar, and one to three phosphate groups.

A

Nucleotide

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3
Q

This is an important precursor for all nucleotides.

A

PRPP

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4
Q

ATP + _________ with the enzyme PRPP synthestase makes PRPP + AMP

A

Ribose-5-phosphate

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5
Q

What are the pyrimidines?

A

Thymine
Cytosine
Uracil

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6
Q

What are the purines?

A

Adenine
Guanine

***PURe As Gold

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7
Q

Pyrimidines form nitrogenous bases independent of _______.

A

PRPP

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8
Q

Pyrimidines are formed in a unidirectional pathway in the cytoplasm. Its precursors are…

A

-NH3 from Gln
Asp
HCO3-

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9
Q

What is the allosteric regulation of pyrimidines?

A 
Pyr inhibit (C)
Pur activates (A/G)
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10
Q

For pyrimidines, synthesis begins with CAD, which stands for…

A

1) Carbamoyl phosphate synthetase II (CPSII)
2) Aspartate transcarbamoylase (ATCase)
3) Dihydroorotase

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11
Q

(Pyrimidines) Step 1 – CPSII has a ________ that allows the reaction from:

_______ – Carboxyphosphate – Carbamic acid – Carbamoyl phosphate

A

Channel

Bicarbonate

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12
Q

(Pyrimidines) The NH3 from Glutamine is added to _________ to form Carbamic acid in the CPSII step.

A

Carboxyphosphate

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13
Q

(Pyrimidines) Step 2 – ATCase adds ________ to carbamoyl phosphate to form carbamoylaspartate.

A

Aspartate

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14
Q

ATCase has two allosteric regulators. ______ activates and _____ inhibits.

A

ATP

CTP

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15
Q

(Pyrimidines) Step 3 – __________ closes the ring, converting carbamoylaspartate into dihydroorotate. It is a hydrolase in reverse (releases water).

A

Dihydroorotase

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16
Q

(Pyrimidines) Step 4 – This is located in the mitochondria and converts Dihyroorotate to Orotate.

A

Dihydroorotate dehydrogenase

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17
Q

(Pyrimidines) Step 5 – This enzyme removes the PPi when Orotate is added to PPRP, thus making Orotidylate.

A

UMP synthetase

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18
Q

(Pyrimidines) Step 6 – Orotidylate is decarboxylated to form _______.

A

Uracil

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19
Q

This disease occurs when cells fail to divide, most commonly because of B9 and/or B12 deficiencies.

A

Megaloblastic anemia

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20
Q

Hereditary Orotic Aciduria symptoms include excessive _______ excreted in the urine and megaloblastic anemia that fails to respond to B9/B12 treatments. This is because it is a deficiency of ______ ______ (can’t convert orotate to uracil).

A

Orotate

UMP synthetase

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21
Q

(Pyrimidines) Step 7 – UMP (uracil) uses a nucleoside monophosphate kinase specific to it to form ______.

A

UDP

***In first phosphorylation, the kinase is specific for each NMP.

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22
Q

(Pyrimidines) Step 8 – UDP uses a nucleoside diphosphate kinase to add a 3rd _________. This kinase has broad specificity and can add to ANY NDP.

A

Phosphate

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23
Q

(Pyrimidines) Step 9 – _____ is the only nucleotide to be synthesized directly as a triphosphate. It is converted in one step from UTP with the addition of an amine group from _______.

A

CTP

Glutamine

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24
Q

CTP synthetase has two allosteric regulators just like we saw with ATCase. _______ activates, and _____ inhibits.

A

GTP

CTP

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25
Q

(Purines) These form a nitrogenous base on _______ with a branched pathway in the cytoplasm.

A

PRPP

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26
Q

What are the precursors used to from purines?

A 
-NH3 from Gln
Gly
Asp
N10-formyl-THF (*Vitamin B9 derivative) 
HCO3-
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27
Q

Purines are regulated by the feedback inhibition of _______.

A

Purines

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28
Q

Purines form ________, the equivalent of Orotate to pyrimidines.

A

IMP (Inosine monophosphate)

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29
Q

(Purines) Reactions 1-3 form the _____-membered ring.

A

5

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30
Q

(Purines) Reactions 4-10 form the ______-membered ring.

A

6

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31
Q

(Purines) Step 1 – Swaps PPi on PRPP for ______ from Gln.

A

-NH3

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32
Q

(Purines) Step 2 – ________ is added.

A

Glycine

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33
Q

(Purines) Step 3 – A formyl group is added from _________ to complete the 5-membered ring.

A

N10-formyl THF

34
Q

(Purines) Step 4 – Adds an ______ from Gln to start the second ring (6-membered).

A

-NH3

35
Q

(Purines) Step 5 – The addition of the -NH3 from Gln in the previous step fully closes the _____-membered ring.

A

5

36
Q

(Purines) Step 6 – Adds ______ from HCO3- first to ______ (N) then to ______ (alpha-C).

A

-CO2
Gln
Gly

37
Q

(Purines) Step 7 – Adds ______ at the carboxyl (from alpha-carbon).

A

Asp

38
Q

(Purines) Step 8 – Releases _______ (broken off from Aspartate).

A

Fumarate

39
Q

(Purines) Step 9 – Second addition of a formyl group from (another) __________, completing the 6-membered ring.

A

N10-formyl THF

40
Q

(Purines) Step 10 – Closes the ____-membered ring, forming ________.

A

6

Hypoxanthine

41
Q

In vertebrates, purines are made in the _________, where 6 enzymes perform 10 reactions.

A

Purinosome

42
Q

(Purines) In the purinosome, reactions _____, _____, and _____ are carried out on 3 individual proteins.

A

1; 4; 8

43
Q

(Purines) In the purinosome, reactions _____, _____, and _____ are carried out on 3 multifunctional proteins.

A

2; 3; 5

44
Q

(Purines) In the purinosome, _____/ _____ and _____/ _____ are carried out separately.

A

6; 7

9; 10

45
Q

(Purines) 2 additional enzymes provide the _________.

A

N10-formyl-THF

46
Q

(Purines) _______ facilitates flow, similar to the channel for pyrimidines.

A

Proximity

47
Q

(Purines) After IMP is formed (first 10 steps) the different nucleotides are formed by _______ off from it.

A

Branching

48
Q

(Purines) To form AMP, uses _____ for energy and replaces the carbonyl with -NH3 from ________. Releases ________ after this, and is inhibited my ______.

A

GTP
Asp
Fumarate
AMP

49
Q

(Purines) To form GMP, uses ______ for energy and there must be a redox with H20 to make the 2nd ________, then it replaces it with -NH3 from _______. It is inhibited by ______.

A

ATP
Carbonyl
Gln
GMP

50
Q

(Purines) After GMP or AMP is made, then it undergoes the same steps as pyrimidines for adding phosphates. Nucleoside monophosphate kinase are (SPECIFIC/BROAD) to each NMP, then nucleoside diphosphate kinase is (SPECIFIC/BROAD) to each NDP.

A

Specific

Broad

51
Q

Converting ribose to deoxyribose requires a ________ reaction.

A

Reduction

52
Q

Deoxyribonucleotides are created from their respective ______, but ________ take a detour.

A

NDPs

Pyrimidines

53
Q

_________ _________ is the enzyme that acts on all NDPs, and can also act on NTPs. After this reaction, the electrons are passed through the creation of ______ ______.

A

Ribonucleotide reductase

Free radicals

54
Q

Class I Ribonucleotide Reductases are found in _______ and humans.

A

E. coli

55
Q

Catalytic Tyr free radical is stabilized by 2 ______ irons.

A

Fe

56
Q

Ribonucleotide reductase makes ______, and _______ provides the necessary electrons for redox reactions.

A

dNDPs

NADPH

57
Q

Ribonucleotide reductase has an active site that is also the ________ site, and 2 allosteric sites, which are a ________ site and an ________ site (on/off switch).

A

Catalytic
Specificity
Activity

58
Q

For ribonucleotide reductase, allosteric binding dictates active site preferences. The activity site is an on/off switch, ______ promotes function and ______ turns off by altering subunit contacts.

A

ATP

dATP

59
Q

For ribonucleotide reductase, the specificity site is a volume dial. If the specificity site has dATP, then the active site prefers _________. If the specificity site has dTTP, then the active site prefers _______ and pyrimidines are inhibited. If the specificity site has dGTP, then the active site prefers _______ and pyrimidines are inhibited (only in vertebrates).

A

Pyrimidines
GDP
ADP

60
Q

All the dNDPs are converted to dNTPs by _______ _______ _______ just like their NDP cousins, but dTTP is special.

A

Nucleoside diphosphate kinase

61
Q

To make dTTP, we first need dUMP, which can be created in two ways:

1) Removal of PPi from ______
2) Deamination of ______

A

dUTP

dCMP

62
Q

Once we have dUMP, then ________ ________ adds a methyl to create dTMP.

A

Thymidylate synthase

63
Q

Dihydrofolate is reduced to form __________ (the active form of Vitamin B9) through the oxidation of NADPH.

A

Tetrahydrofolate (THF)

64
Q

Several cancer chemotherapy drugs act upon enzymes in the detour of dUMP to dTMP (pyrimidines). This halts the formation of deoxyribose pyrimidines, which can’t make DNA. If you can’t make DNA then cells can’t ________. This stops cancer in its tracks.

A

Divide

65
Q

Endonucleases cut in the _______, while exonucleases chew from the _______.

A

Middle

Ends

66
Q

Pyrimidines use ________ and ________ for salvage in two steps.

A

Phosphorylases

Kinases

67
Q

Pyrimidines use phosphorylases and kinases for salvage in two steps. Phosphorylases make _________ and kinases make _________.

A

Nucleosides

Nucleotides

68
Q

Viral Thymidine Kinase is not as discriminating as human Thymidine Kinase – It will accept purines as well as T’s. ________ will bind tightly to Thymidine Kinase, but will not interact with human Thymidine Kinase. ________ ________ can be incorporated into viral DNA, where it terminates synthesis.

A

Acyclovir

Acyclovir Triphosphate

69
Q

Purines use ___________ to salvage in one step. Adds back to PRPP.

A

Phosphoribosyltransferases

70
Q

Adenine phosphoribosyltransferase makes _____ (adenine + PRPP).

A

AMP

71
Q

Hypoxanthine-Guanine phosphoribosyltransferase (HGPRT or HPRT) makes ______/_____ (Guanine + PRPP or Hypoxanthine + PRPP).

A

IMP; GMP

72
Q

Nitrogenous bases can be broken down. ______ ______ is the final product of purine catabolism.

A

Uric acid

73
Q

Beta-Ureidopropionic acid can be converted to ________ + _______ + _______ by the enzyme Ureidopropionase to complete pyrimidine catabolism.

A

Alanine
CO2
NH3

74
Q

Uric acid, like glutathione, is an _________.

A

Antioxidant

75
Q

T/F. Uric acid/Urate is insoluble.

A

True

76
Q

Urate Oxidase solubilizes urate, at the cost of its ________ potential. Humans and the great apes have mutate Urate Oxidase genes.

A

Antioxidant

77
Q

At high concentrations, urate crystallizes. Chronic elevated levels of urate in the blood (hyperuricemia) results in uric acid crystals collecting in joints, which is called _______.

A

GOUT

78
Q

Symptoms of _______ include inflammation, arthritis, and joint degradation.

A

GOUT

79
Q

Many pathologies can produce gout symptoms, one is _______ deficiency (Lesch-Nyhan syndrome).

A

HPRT

80
Q

Severe Combine Immunodeficiency Disease (SCID) is actually a deficiency of ________ ________ (this enzyme is involved in the catabolic pathway, it helps degrade purines to Uric acid).

A

Adenosine deaminase

81
Q

Without Adenosine Deaminase, dAMP accumulates. dAMP is converted to dATP by salvage pathway enzymes, and dATP inhibits _________ _________. Deoxyribonucleotides are not produced, DNA cannot be synthesized, cells do not proliferate.

A

Ribonucleotide reductase

Biochem Exam 3 (10 decks)

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