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Medical Biochemistry > Nucleotide Metabolism > Flashcards

Nucleotide Metabolism Flashcards

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USMLE® Step 1 flashcards
1
Q

What are the components of a nucleotide?

A

sugar, nitrogenous base, and phosphate group

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2
Q

What are the names of all the nucleotides?

A

adenosine monophosphate
guanosine monophosphate
inosine monophosphate

cytidine monophosphate
uridine monophosphate
thymidine monophosphate

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3
Q

What are the components of a nucleoside?

A

sugar, nitrogenous base

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4
Q

what are the names of all the nucleosides?

A

adenosine
guanosine
inosine

cytidine
uridine
thymidine

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5
Q

What are the names of the nucleic acids?

A

adenine
guanine
hypoxanthine

thymine
uracil
cytosine

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6
Q

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

A

Uracil

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7
Q

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

A
  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)
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8
Q

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

A
  1. ) Sugar Activation

2. ) Nitrogenous Base Building

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9
Q

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

A
  1. ) Build the Nitrogenous Base

2. ) Add Sugar Ring

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10
Q

What are the sources of the pyrimidine nitrogenous ring?

A

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

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11
Q

What are the sources of the purine nitrogenous ring?

A

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

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12
Q

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

A

4 ATP/ IMP

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13
Q

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

A

3 ATP/UMP

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14
Q

Tell me the stages of Purine Anabolism

A
  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
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15
Q

What is the committed step of purine anabolism?

A

GLUTAMINE: PHOSPHORIBSOYL PYROPHOSPHATE TRANSAMINASE

The activation of the PRPP ring with NH3

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16
Q

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

A

Fumarate

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17
Q

IMP is converted to Adenylosuccinate Monophosphate through through which enzyme?

A

ADENYLOSUCCINATE SYNTHETASE

18
Q

What enzyme converts IMP–> XMP?

A

IMP Dehydrogenase

19
Q

What enzyme converts Xanthine monophosphate to GMP?

A

GMP Synthetase

20
Q

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

A

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

21
Q

How does Methotrexate inhibit purine synthesis? What is it?

A

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

22
Q

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

A

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.

23
Q

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

A

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.

24
Q

What is the function of phosphodiesterases?

A

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

25
Q

What is the function of nucleotidases?

A

Cleaves nucleotides–> nucleosides + Pi

26
Q

What is the function of nucleosidases?

A

Cleaves nucleosides–> nucleic acid + sugar

27
Q

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

A 
HGPRT Enzyme (Hypoxanthine & Guanine)
 APRT Enzyme (Adenine)-->
Use PRPP + nucleic acid--> nucleotide + PPi
28
Q

What is the committed step in Human Pyrimidine Synthesis?

A

Creation of Carbamoyl P via Carbomyl Synthase II

29
Q

What is the committed step in Bacterial Pyrimidine Synthesis?

A

Creation of N-carbamoylaspartate via ATCase (aspartate transcarbamoylase)

30
Q

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

A
  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
31
Q

What enzyme converts UTP–> CTP?

A

CTP synthase

32
Q

What enzyme converts UDP–> dUDP?

A

Ribonucleotide Reductase

33
Q

What enzyme converts dUMP–> dTMP?

A

Thymidylate Synthase

34
Q

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

A

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

35
Q

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

A

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

36
Q

what is the function of ribonucleases/ deoxyribonucleases?

A

Breaks oligonucleotides–> shorter nucleotides sequences

37
Q

What is Oritic Aciduria and how do you treat it?

A

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

38
Q

What is Adenosine Deaminase (ADA)?

A

ADA is a molecule that reduces AMP–>Adenosine

39
Q

What happens due to overproduction of Adenosine Deaminase?

A

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

40
Q

what happens due to underproduction of Adenosine Deaminase?

A

SCID Disorder

41
Q

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

A

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)

42
Q

What is Lesch-Nyhan Syndrome?

A

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.

Medical Biochemistry (13 decks)

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