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Flashcards in Lecture 50 Deck (38)
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1
Q

What are 6 key roles of nucleotides in cellular processes?

A

1) Activated precursors of RNA & DNA
2) Adenine nucleotides are components of the major co-enzymes: NAD, NADP, FMN, FAD, & CoA
3) Nucleotide derivatives are activated intermediates in biosynthetic processes (UDP-glucose, SAM)
4) Serve as metabolic regulators (e.g. cAMP and the activation of cell signaling)
5) Serve as major currency of energy in all cells (ATP & GTP)
6) Several metabolic diseases have their etiology in nucleotide metabolism

2
Q

What are the purine DNA nucleotide bases?

A

1) Adenine

2) Guanine

3
Q

What are the pyrimidine DNA nucleotide bases?

A

1) Thymine

2) Cytosine

4
Q

What are the purine RNA nucleotide bases?

A

1) Adenine

2) Guanine

5
Q

What are the pyrimidine RNA nucleotide bases?

A

1) Uracil

2) Cytosine

6
Q

What is the difference between adenine, adenosine, & adenosine monophosphate (AMP)?

A

1) Adenine is a base
2) Adenosine contains the adenine base in addition to a ribose sugar (or deoxyribose)
3) Adenosine monophosphate (AMP) contains the adenine base, a ribose (or deoxyribose sugar), & a phosphate group

7
Q

How can you form a diphosphate?

A

Using nucleoside monophosphate kinase & a tri-phosphate, you can phosphorylate a monophosphate to form a diphosphate

8
Q

How can you form a triphosphate?

A

Using nucleoside diphosphate kinase & a tri-phosphate, you can phosphorylate a diphosphate to form a triphosphate

9
Q

What are two common purine bases aside from adenine and guanine?

A

1) Hypoxanthine (6 oxy purine)
2) Xanthine (2,6 dioxy purine)
3) Adenine (6 amino purine)
4) Guanine (2 amino, 6-oxy purine)

10
Q

What are two biosynthetic pathways for obtaining purine and pyrimidine bases?

A

1) De novo pathway (building the bases from non-purine molecules)
2) Salvage pathway (the reutilization of bases from dietary or catabolic sources)

11
Q

How can you form uracil from cytosine?

A

Oxidative deamination

12
Q

Which of the following types of cells has the highest activity of ribonucleotide reductase and why? (Epithelial, nerve, or muscle)

A

When there is a need for DNA synthesis in a cell, such as in a rapidly dividing cell, RNA will be converted to DNA by Ribonucleotide reductase. This occurs most often in an epithelial cell, which needs to rapidly divide

13
Q

When a pharmaceutical company produces a purine or pyrimidine based drug, it is best administered as a base, nucleoside, or nucleotide?

A

Nucleoside because it is unphosphorylated and can easily cross the cell membrane

14
Q

What is a byproduct of the pentose phosphate pathway that is used in the biosynthesis of purines?

A

Ribose 5-phosphate

15
Q

What is the first step of purine biosynthesis in the de novo pathway?

A

1) Ribose 5-phosphate + ATP → PRPP + AMP (uses ribose phosphate pyrophospho-kinase (PRPP) synthetase)
2) Can be inhibited by products IMP, AMP & GMP through feedback inhibition

16
Q

Once PRPP is formed, what is the first unique step to purine biosynthesis in the de novo pathway?

A

1) Phosphate pyrophospho-kinase (PRPP) + Glutamine → 5-phosphoribosylamine + Glutamate + PPi
2) Can be inhibited by products IMP, AMP, & GMP through feedback inhibition

17
Q

Describe the de novo pathway of purine biosynthesis

A

1) It is a nonregulatory pathway (once it begins, it goes to completion)
2) The end product is Inosine Mono-Phosphate (IMP)
3) The Nitrogens that make up IMP are taken from aspartate, glycine, & glutamine
4) The carbons that make up IMP are taken from 10-formyl THF, 5,10-methenyl THF, CO2, & Glycine

18
Q

What is Inosine Monophosphate (IMP) used for?

A

It is a precursor for both AMP & GMP

19
Q

How is AMP formed from IMP?

A

1) IMP + Aspartic Acid + GTP → Adenylosuccinate + GDP (uses Adenylosuccinate synthetase)
2) Adenylosuccinate → Fumarate + AMP (uses Adenylosuccinase)
3) The presence of GTP positively regulates this pathway

20
Q

How is GMP formed from IMP?

A

1) IMP + H2O + NAD+ → Xanthosine monophosphate + NADH + H+ (uses IMP dehydrogenase)
2) Xanthosine monophosphate + Glutamine + ATP → GMP + Glutamate + AMP + PPi (uses GMP synthetase)
3) The presence of ATP positively regulates this pathway

21
Q

How is Adenine formed from Hypoxanthine-IMP?

A

Hypoxanthine-IMP + Aspartate → Adenine (Aspartate donates N)

22
Q

How is Guanine formed from Xanthine-XMP?

A

Xanthine-XMP + Glutamine → Guanine (Glutamine donates N)

23
Q

What is unique about the salvage pathways of purine synthesis?

A

Instead of synthesizing new purines (like the de novo pathway), it re-utilizes existing purines

24
Q

What are two main enzymes with different specificities associated wit the salvage pathways?

A

1) Adenine phosphoribosyl transferase (APRT)

2) Hypoxanthine-guanine phosphoribosyl transferase (HGPRT)

25
Q

Describe the reaction catalyzed by APRT

A

PRPP + Adenine → AMP

26
Q

Describe the reaction catalyzed by HGPRT

A

PRPP + Hypoxanthine/Guanine → IMP/GMP

27
Q

What enzyme catalyzes the degradation of a nucleotide into a nucleoside?

A

Nucleotidase

28
Q

What enzyme catalyzes the degradation of a nucleoside into a base?

A

Phosphorylase

29
Q

What are two diseases correlated with a deficiency in HGPRT?

A

Gaut & Lesch–Nyhan syndrome

30
Q

How can adenosine be degraded to uric acid?

A

1) Adenosine + H2O → Inosine + NH4+ (uses Adenosine deaminase (ADA))
2) Isosine + Pi → Hypoxanthine + Ribose-1-phosphate (uses purine nucleoside phosphorylase)
3) Hypoxanthine → Xanthine (uses xanthine oxidase)
4) Xanthine → Uric Acid (uses xanthine oxidase)

31
Q

How can guanosine be degraded to uric acid?

A

1) Guanosine + Pi → Guanine + ribose-1-phosphate (uses purine nucleoside phosphorylase)
2) Guanine + H2O → Xanthine + NH4+ (uses guanine deaminase)
3) Xanthine → Uric Acid (uses xanthine oxidase)

32
Q

What causes Gout?

A

Gout results from hyperuricemia. This can be caused by:

1) Decreased Uric Acid excretion: 80% of gout – idiopathic, renal disease, diabetes insipidus, hypertension, Downs syndrome, & many others
2) Increased Uric Acid production: 20% of gout
a) PRPP synthetase overactivity, hemolytic diseases, lymphoproliferative disease, & many others
b) HGPRT deficiency (Lesch-Nyhan syndrome)

33
Q

What exacerbates gout?

A

1) Alcohol
2) Purine rich diet
3) Obesity

34
Q

How exactly does PRPP synthetase overactivity lead to gout?

A

Lost regulation of PRPP synthetase allows it to continuously convert Ribose 5-phosphate to phosphoribosyl amine, which is then converted to purines. When there is an excess of purines, they must be degraded into uric acid

35
Q

How exactly does HGPRT deficiency lead to gout?

A

Without HGPRT, PRPP + Guanine cannot be converted to GMP. There is therefore a buildup of guanine, resulting in elevated uric acid levels

36
Q

How can gout be treated?

A

Administration of allopurinol inhibits xanthine oxidase, causing:

1) Decrease urate
2) Increase xanthine & hypoxanthine
3) Decrease PRPP

37
Q

What is Lesch-Nyhan syndrome?

A

1) X-linked recessive
2) Severe HGPRT deficiency, which causes decreased IMP & GMP, & Increased PRPP & de novo purine pathway
3) Hyperuremia: gouty arthritis, kidney stones, tophi
4) Neurologic disability: spasticity & hyperreflexia
5) Behavioral problems: cognitive dysfunction, aggression, & self-injury

38
Q

What is SCIDS (Severe Combined Immunodeficiency Syndrome)?

A

1) Autosomal recessive disorder
2) Mutations in Adenosine Deaminase (ADA) causes a deficiency of ADA
3) Infants subject to bacterial, candidiasis, viral, & protozoal infections
4) A buildup of of dATP is toxic and causes reduction of both T band C cells