Nucleotide Metabolism

Question 1

What are the components of a nucleotide?

Answer 1

sugar, nitrogenous base, and phosphate group

Question 2

What are the names of all the nucleotides?

Answer 2

adenosine monophosphate
guanosine monophosphate
inosine monophosphate

cytidine monophosphate
uridine monophosphate
thymidine monophosphate

Question 3

What are the components of a nucleoside?

Answer 3

sugar, nitrogenous base

Question 4

what are the names of all the nucleosides?

Answer 4

adenosine
guanosine
inosine

cytidine
uridine
thymidine

Question 5

What are the names of the nucleic acids?

Answer 5

adenine
guanine
hypoxanthine

thymine
uracil
cytosine

Question 6

Which nucleic acid is the only nucleic acid that is NOT part of DNA?

Answer 6

Uracil

Question 7

What are the specific roles/functions of nucleotides and nucleosides in metabolism?

Answer 7

1. ) They act as co-substrates for many rxns
2. ) They are components of cofactors
3. ) Play a regulatory role in cellular signaling (cAMP, cGMP)
4. ) Make important biomolecules (Vitamin B12)

Question 8

What is the order of component addition for De Novo Purine Synthesis?

Answer 8

1. ) Sugar Activation

2. ) Nitrogenous Base Building

Question 9

What is the order of component addition for De Novo Pyrimidine Synthesis?

Answer 9

1. ) Build the Nitrogenous Base

2. ) Add Sugar Ring

Question 10

What are the sources of the pyrimidine nitrogenous ring?

Answer 10

Asparagine, Glutamate, HCO3-: N5,N10-Methylene THF

Question 11

What are the sources of the purine nitrogenous ring?

Answer 11

Asparagine, Glutamate, Glycine, N10-Formyl THF, CO2

Question 12

In order to get to the precursor nucleotide for purine synthesis of AMP + GMP, what is the ATP requirement?

Answer 12

4 ATP/ IMP

Question 13

In order to get to the precursor nucleotide for pyrimidine synthesis of CMP + TMP, what is the ATP requirement?

Answer 13

3 ATP/UMP

Question 14

Tell me the stages of Purine Anabolism

Answer 14

1. ) R-5-P activation–> PRPP
2. ) PRPP–> Phosphoribosylamine
3. ) Addition of Gln, Asn, Gly, CO2, N5,N10-Methylene THF to create hypoxanthine base to get IMP
4. ) IMP–> GMP or AMP

Question 15

What is the committed step of purine anabolism?

Answer 15

GLUTAMINE: PHOSPHORIBSOYL PYROPHOSPHATE TRANSAMINASE

The activation of the PRPP ring with NH3

Question 16

What is the name of the TCA intermediate that if fed into the TCA cycle during the creation of AMP?

Answer 16

Fumarate

Question 17

IMP is converted to Adenylosuccinate Monophosphate through through which enzyme?

Answer 17

ADENYLOSUCCINATE SYNTHETASE

Question 18

What enzyme converts IMP–> XMP?

Answer 18

IMP Dehydrogenase

Question 19

What enzyme converts Xanthine monophosphate to GMP?

Answer 19

GMP Synthetase

Question 20

what is the role of a nucleotide reductase in nucleotide anabolism?

Answer 20

It reduces the 2’ OH group to a 2’ H group which creates a deoxyribonucleic acids.

Question 21

How does Methotrexate inhibit purine synthesis? What is it?

Answer 21

Methotrexate is an anti-cancer drug that works as a competitive inhibitor to folic acid by competing for DHF reductases active site. This causes decreased production of IMP–> decreased purine synthesis.

Km of Methotrexate –> 100x AFFINITY compared to FOLIC ACID

Question 22

Why are sulfa drugs like sulfanamides (sulfa drugs) used so heavily for the treatment of a bacterial infection?

Answer 22

Sulfanimides (sulfa drugs) selectively work on bacterial cell processes of THF production by prohibiting the binding of PABA to create folic acid–> stopping cell division through lack of nucleotide synthesis.

Question 23

What is the idea of cross regulation and how does that pertain to AMP/GMP synthesis?

Answer 23

Cross regulation is the idea that AMP synthesis is regulated by [GTP]. Enzymes like adenylosuccinate synthetase + adenylosuccinase –> (+) GTP

GMP Synthesis via IMP Dehydrogenase & GMP Synthetase IS regulated by ATP.

Question 24

What is the function of phosphodiesterases?

Answer 24

Cleaves the phosphodiester bonds formed between the 5’ Phosphate and the 3’ OH groups.

Question 25

What is the function of nucleotidases?

Answer 25

Cleaves nucleotides--> nucleosides + Pi

Question 26

What is the function of nucleosidases?

Answer 26

Cleaves nucleosides--> nucleic acid + sugar

Question 27

What are the names of the enzymes that are very important to purine salvage pathway and how do they work?

Answer 27

``` HGPRT Enzyme (Hypoxanthine & Guanine) APRT Enzyme (Adenine)--> Use PRPP + nucleic acid--> nucleotide + PPi ```

Question 28

What is the committed step in Human Pyrimidine Synthesis?

Answer 28

Creation of Carbamoyl P via Carbomyl Synthase II

Question 29

What is the committed step in Bacterial Pyrimidine Synthesis?

Answer 29

Creation of N-carbamoylaspartate via ATCase (aspartate transcarbamoylase)

Question 30

What are the major steps in De Novo Pathway for pyrimidine synthesis?

Answer 30

1. ) Build the Orotate Ring in the mitochondria 2. ) Add the PRPP to Orotate Ring in the Cytosol 3. ) Create UMP in Cytosol as a result--> dTMP, CTP

Question 31

What enzyme converts UTP--> CTP?

Answer 31

CTP synthase

Question 32

What enzyme converts UDP--> dUDP?

Answer 32

Ribonucleotide Reductase

Question 33

What enzyme converts dUMP--> dTMP?

Answer 33

Thymidylate Synthase

Question 34

What is the affect of 5-flourouracil? What is it used for?

Answer 34

5-Florouracil is used as an anti-cancer drug that stops thymidylate synthase from producing dTMP--> STOPS DNA PRODUCTION

Question 35

What is the affect of acyclovir? What is it used for?

Answer 35

Acyclovir is an antiviral drug used to inhibit thymidine kinase which makes dTMP--> dTDP-->dTTP

Question 36

what is the function of ribonucleases/ deoxyribonucleases?

Answer 36

Breaks oligonucleotides--> shorter nucleotides sequences

Question 37

What is Oritic Aciduria and how do you treat it?

Answer 37

Orotic Aciduria is the build up of orotate because a dysfunction in UMP synthase enzyme. **Causes megalobastic anemia! It can be compensated by Uridine/UMP supplementation

Question 38

What is Adenosine Deaminase (ADA)?

Answer 38

ADA is a molecule that reduces AMP-->Adenosine

Question 39

What happens due to overproduction of Adenosine Deaminase?

Answer 39

Cells do NOT have enough AMP because all the enzymes (ADA) are converting Adenosine to Inosine.

Question 40

what happens due to underproduction of Adenosine Deaminase?

Answer 40

SCID Disorder

Question 41

What is Xanthine Oxidase and how does it relate to GOUT Disease.

Answer 41

Xanthine Oxidase is a purine salvage enzyme that breaks down Hypoxanthine--> Xanthine & Xanthine--> Uric Acid. The accumulation of Uric Acid causes gout crystals that build up in joints of the big toe and hands. (METATARSAL PHALYNGEAL JOINT)

Question 42

What is Lesch-Nyhan Syndrome?

Answer 42

Lesch Nyan syndrome is a defect in HGPRT enzyme that converts nucleic acids--> nucleosides especially hypoxanthine-->IMP and guanine--> GMP. When HGPRT enzyme is affected--> build up HYPOXANTHINE--> URIC ACID BUILD UP ( INCREASED XANTHINE OXIDASE ACTIVITY) Sx: Self-Mutilation, kidney stones, poor muscle control, mental retardation, etc.