30 - Nucleotide Metabolism

Question 1

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

Answer 1

Nucleoside

Question 2

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

Answer 2

Nucleotide

Question 3

This is an important precursor for all nucleotides.

Answer 3

PRPP

Question 4

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

Answer 4

Ribose-5-phosphate

Question 5

What are the pyrimidines?

Answer 5

Thymine
Cytosine
Uracil

Question 6

What are the purines?

Answer 6

Adenine
Guanine

***PURe As Gold

Question 7

Pyrimidines form nitrogenous bases independent of _______.

Answer 7

PRPP

Question 8

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

Answer 8

-NH3 from Gln
Asp
HCO3-

Question 9

What is the allosteric regulation of pyrimidines?

Answer 9

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

Question 10

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

Answer 10

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

Question 11

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

_______ – Carboxyphosphate – Carbamic acid – Carbamoyl phosphate

Answer 11

Channel

Bicarbonate

Question 12

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

Answer 12

Carboxyphosphate

Question 13

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

Answer 13

Aspartate

Question 14

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

Answer 14

ATP

CTP

Question 15

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

Answer 15

Dihydroorotase

Question 16

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

Answer 16

Dihydroorotate dehydrogenase

Question 17

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

Answer 17

UMP synthetase

Question 18

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

Answer 18

Uracil

Question 19

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

Answer 19

Megaloblastic anemia

Question 20

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).

Answer 20

Orotate

UMP synthetase

Question 21

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

Answer 21

UDP

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

Question 22

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

Answer 22

Phosphate

Question 23

(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 _______.

Answer 23

CTP

Glutamine

Question 24

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

Answer 24

GTP

CTP

Question 25

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

Answer 25

PRPP

Question 26

What are the precursors used to from purines?

Answer 26

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

Question 27

Purines are regulated by the feedback inhibition of _______.

Answer 27

Purines

Question 28

Purines form ________, the equivalent of Orotate to pyrimidines.

Answer 28

IMP (Inosine monophosphate)

Question 29

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

Answer 29

5

Question 30

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

Answer 30

6

Question 31

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

Answer 31

-NH3

Question 32

(Purines) Step 2 -- ________ is added.

Answer 32

Glycine

Question 33

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

Answer 33

N10-formyl THF

Question 34

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

Answer 34

-NH3

Question 35

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

Answer 35

5

Question 36

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

Answer 36

-CO2 Gln Gly

Question 37

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

Answer 37

Asp

Question 38

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

Answer 38

Fumarate

Question 39

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

Answer 39

N10-formyl THF

Question 40

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

Answer 40

6 | Hypoxanthine

Question 41

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

Answer 41

Purinosome

Question 42

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

Answer 42

1; 4; 8

Question 43

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

Answer 43

2; 3; 5

Question 44

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

Answer 44

6; 7 | 9; 10

Question 45

(Purines) 2 additional enzymes provide the _________.

Answer 45

N10-formyl-THF

Question 46

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

Answer 46

Proximity

Question 47

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

Answer 47

Branching

Question 48

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

Answer 48

GTP Asp Fumarate AMP

Question 49

(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 ______.

Answer 49

ATP Carbonyl Gln GMP

Question 50

(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.

Answer 50

Specific | Broad

Question 51

Converting ribose to deoxyribose requires a ________ reaction.

Answer 51

Reduction

Question 52

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

Answer 52

NDPs | Pyrimidines

Question 53

_________ _________ 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 ______ ______.

Answer 53

Ribonucleotide reductase | Free radicals

Question 54

Class I Ribonucleotide Reductases are found in _______ and humans.

Answer 54

E. coli

Question 55

Catalytic Tyr free radical is stabilized by 2 ______ irons.

Answer 55

Fe

Question 56

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

Answer 56

dNDPs | NADPH

Question 57

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).

Answer 57

Catalytic Specificity Activity

Question 58

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.

Answer 58

ATP | dATP

Question 59

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).

Answer 59

Pyrimidines GDP ADP

Question 60

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

Answer 60

Nucleoside diphosphate kinase

Question 61

To make dTTP, we first need dUMP, which can be created in two ways: 1) Removal of PPi from ______ 2) Deamination of ______

Answer 61

dUTP | dCMP

Question 62

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

Answer 62

Thymidylate synthase

Question 63

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

Answer 63

Tetrahydrofolate (THF)

Question 64

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.

Answer 64

Divide

Question 65

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

Answer 65

Middle | Ends

Question 66

Pyrimidines use ________ and ________ for salvage in two steps.

Answer 66

Phosphorylases | Kinases

Question 67

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

Answer 67

Nucleosides | Nucleotides

Question 68

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.

Answer 68

Acyclovir | Acyclovir Triphosphate

Question 69

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

Answer 69

Phosphoribosyltransferases

Question 70

Adenine phosphoribosyltransferase makes _____ (adenine + PRPP).

Answer 70

AMP

Question 71

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

Answer 71

IMP; GMP

Question 72

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

Answer 72

Uric acid

Question 73

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

Answer 73

Alanine CO2 NH3

Question 74

Uric acid, like glutathione, is an _________.

Answer 74

Antioxidant

Question 75

T/F. Uric acid/Urate is insoluble.

Answer 75

True

Question 76

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

Answer 76

Antioxidant

Question 77

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 _______.

Answer 77

GOUT

Question 78

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

Answer 78

GOUT

Question 79

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

Answer 79

HPRT

Question 80

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).

Answer 80

Adenosine deaminase

Question 81

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.

Answer 81

Ribonucleotide reductase