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EOM Test 2 > Nucleotide Metabolism 1 > Flashcards

Nucleotide Metabolism 1 Flashcards

1
Q

Where do most of our purines and pyrimidines for nucleotide synthesis?

A

Synthesized from amphibolic intermediate

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2
Q

What is a basic difference between the order of purine and pyrimidine synthesis?

A

Purine - start with sugar, then build purine ring

Pyrimidine - build the pyrimidine ring, then attach sugar

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3
Q

What is the first reaction in purine synthesis?

A

Ribose-5-phosphate to

Phosphoribosyl pyrophosphate(PRPP)

Enzyme: PRPP Synthase

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4
Q

What five molecules are used to build the purine ring?

A 
ATP
Glutamine
Tetrahydrofolate
Aspartate
Glycine
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5
Q

What molecule is the branch point for purine synthesis?

A

Inosine monophosphate (IMP)

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6
Q

What is the major site of purine synthesis?

A

Liver

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7
Q

What inhibits PRPP Synthase?

A

AMP and GMP

Purine nucleotides

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8
Q

What is the committed step of De Novo purine synthesis?

A

PRPP to 5-phosphoribosylamine

Enzyme: glutamine PRPP amidotransferase

(Aka PRPP Glutamyl Amidotransferase)

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9
Q

What are the inhibitors of Glutamine PRPP amidotransferase?

A

ATP, ADP, and AMP at one site

GTP, GDP, and GMP at another

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10
Q

What stimulates glutamine PRPP amidotransferase?

A

PRPP

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11
Q

What occurs during the purine synthesis steps involving glutamine?

A

The addition of a nitrogen group to the ring

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12
Q

What occurs during the purine synthesis steps that involve folic acid?

A

Addition of carbonyl to the purine ring

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13
Q

What is the base of IMP?

A

Hypoxanthine

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14
Q

What stimulates the production of AMP?

A

GTP

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15
Q

What stimulates the production of GMP?

A

ATP

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16
Q

What is Azaserine?

A

Glutamine analog that blocks purine synthesis steps involving glutamine

Primarily used in research.

17
Q

What are sulfonamides and why are they used?

A

Inhibit folate metabolism in bacteria by competitively inhibiting PABA

18
Q

What is methotrexate and what is its mechanism?

A

A folate analog that competitively inhibits dihydrofolate reductase

Used in cancer chemotherapy

19
Q

What two disorders are caused by a folic acid deficiency?

A

Anencephaly

Spinal Bifida

20
Q

Why does folic acid deficiency cause neural tube defects?

A

Rapidly dividing cells require large amounts of nucleotides, without folic acid can’t keep up with demand, causing delays in neural folding.

21
Q

What reciprocal relationship exists between AMP and GMP formation?

A

ATP is a substrate for GMP synthesis

GTP is a substrate for AMP synthesis

22
Q

What is purine salvage?

A

Synthesis of nucleotides from purine bases and nucleosides

23
Q

What two enzymes are involved in the purine salvage pathway?

A

Adeninephosphoribosyltransferase

APRT

Hypoxanthine-Guanine PhosphoRibosylTransferase

HGPRT

24
Q

What is Lesch-Nyhan Syndrome?

A

Deficiency or complete lack of HGPRT

Gout and kidney stones

Neurological problems

Self-mutilation

X-linked recessive

25
Q

What is the mechanism for Lesch-Nyhan Syndrome?

A

Lack of HGPRT causes the build up of PRPP, leading to purine overproduction, and therefore degradation and uric acid build up

Brain relies on salvage, so decreased purine production in brain

26
Q

What is the function of purine nucleoside phosphorylase

A

Removes sugar to yield a free base (hypoxanthine or guanine)

27
Q

What is the final product of purine degradation and what is its biological significance?

A

Uric Acid

Can catch free radicals

However, insoluble and can percipitate
-kidney stones, gout

28
Q

What causes gout?

A

Caused by precipitation of urate

Result of excess purine production or partial deficiency in HGPRT

29
Q

What is allopurinol and what is used for?

A

Xanthine analog that blocks xanthine oxidase.

This prevents the formation of uric acid and can prevent gout.

30
Q

What is Purine nucleoside phosphorylase deficiency?

A

Defect in the enzyme

Autosomal recessive disorder

Causes immunodeficiency - no T cells

Rare

31
Q

What is ADA deficiency?

A

Lack of adenosine deaminase

Autosomal recessive

Causes Severe combined immunodeficiency (SCID)

Destruction of B and T lymphocytes

EOM Test 2 (20 decks)

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