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[OS 201] 3rd Exam > Trans - Metabolism of Nucleotides > Flashcards

Trans - Metabolism of Nucleotides Flashcards

1
Q

Examples of Purines (2)

A

Adenine

Guanine

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2
Q

Examples of Pyrimidines (3)

A

Cytosine
Thymine
Uracil

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3
Q

Differentiate a Ribose and a Deoxyribose

A

Main difference is that the hydroxyl group (OH) at Carbon 2 in ribose is replaced by hydrogen (H) in deoxyribose
Difference renders RNA backbone susceptible to base catalyzed hydrolysis

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4
Q

[Nucleoside]

Components

Where is sugar attached in Purines and Pyrimidines?

A

Base + Sugar

Purine: N-9
Pyrimidine: N-1

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5
Q

[Nucleotide]

Components

Where is Phosphate attached in Ribose and Deoxyribose?

A

Base + Sugar + Phosphate

Ribose: C5 (Possibly C2/C3)
Deoxyribose: C3

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7
Q

Nucleotides are joined together via?

A

Phosphodiester Bonds

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8
Q

Polymerization of NAs from Nucleoside Monophosphates occur through?

A

Dehydration

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9
Q

Polymerization of NAs from Nucleoside Triphosphates occur through?

A

Phosphoanhydride bond destruction and pyrophosphate removal

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10
Q

Degradation of NAs occur through?

A

Hydrolysis of covalent linkages

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11
Q

Fate of Sugar and Nitrogenous Bases

A

Sugar: Absorbed like carbohydrates
Bases: Excreted; Purines are excreted as Uric Acid

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12
Q

Are nucleotides essential?

A

No they are not, the body is capable of synthesizing them

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13
Q

Examples of Metabolic Precursors (5)

A
  1. Amino Acids
  2. Ribose-5-Phosphate
  3. CO2
  4. 1-C Groups
  5. NH3
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14
Q

Pathway of Digestion of Dietary Nucleic Acids

A
  1. Nucleic acids ingested in the form of nucleoproteins - like proteins, denaturated by acidity in the stomach
  2. Denatured nucleic acids subjected to nucleases –> result to oligonucleosides (shorter chains

)3. Further cleaved by phosphodiesterase, which cleave phosphodiester bonds one at a time

  1. Nucleases and phosphodiesterase cleave oligonucleotides into mononucleotides
  2. Nucleotidases dephosphorylate mononucleotides into nucleosides
  3. Nucleosidases split the nucleosides further into sugar and base
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15
Q

[Purine De Novo Synthesis]

Parent Purine Nucleotides (2)

A

AMP

GMP

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16
Q

[De Novo Synthesis Linear Pathway]

What is the enzyme that catalyzes the rate-limiting step of the pathway?

A

PRPP Amidotransferase

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17
Q

[De Novo Synthesis Linear Pathway

]Why is PRPP Synthetase not the rate-limiting step?

A

The product, PRPP, can still be used for other reactions

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18
Q

[De Novo Synthesis Linear Pathway]

What is the first intermediate with a complete purine ring?

A

IMP

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19
Q

[De Novo Synthesis Branched Pathway]

IMP could be converted to? How?

A

GMP: NH2 at C2 from Gln, requires ATP

AMP: NH2 at C6 from Asp; requires GTP

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20
Q

[De Novo Synthesis Branched Pathway

]Why is ATP invested to produce GMP from IMP while GTP is used to produce AMP?

A

It is a form of REGULATION. Goal is to have equimolar amounts of AMP and GMP.

21
Q

[Purine De Novo Synthesis

]What is the starting material where atoms are successively added?

22
Q

[Purine De Novo Synthesis]

Purine ring is derived from?

23
Q

[Purine De Novo Synthesis]

Donors of Atoms to Purine Ring (2)

A

Amino Acids

1-C Compounds

24
Q

[Purine De Novo Synthesis]

How much ATP used in the process?

25
Q

[Purine De Novo Synthesis]

Where does it occur?

A

Cytosol of the Liver

26
Q

[Pyrimidine De Novo Synthesis]

What is the rate regulated step?

A

Carbamoyl Phosphate Synthetase II (CPSII)

27
Q

2 Pathways that Lead to Nucleotides

A
  1. De Novo2. Salvage
28
Q

[Pyrimidine De Novo Synthesis]

Compare the two types of CPS by

  1. Tissue
  2. Cellular Location
  3. Pathway
  4. Substrate
A

CPS I

  1. Liver
  2. Mitochondrial Matrix
  3. Urea Cycle
  4. NH

CPS II

  1. All tissues
  2. Cytosol
  3. Pyrimidine Synthesis
  4. Amide of Gln (Glutamine)
29
Q

[Pyrimidine De Novo Synthesis]

Regulation of CPS II

A

UPM: Complete Inhibitor
PRPP: Activator

30
Q

[Pyrimidine De Novo Synthesis]

Ring is derived from? (3)

A

Asp
CO2
Amide of Gln

31
Q

[Salvage Reactions]

What occurs here?

A

Recycling of free purine/pyrimidine bases and nucleotides released from NA degradation

32
Q

[Salvage Reactions]

Where does it occur? Which pathway is more expensive?

A

Non-hepatic cells

De Novo Synthesis is more expensive

33
Q

[Purine Salvage]

What are the 3 Salvage Pathways?

A
  1. Hypoxanthine -> IMP
  2. Guanine -> GMP
  3. Adenine -> AMP
34
Q

[Purine Salvage]

What donates R5P in this pathway?

35
Q

What is Lesch-Nyhan Syndrome?

What are the side effects?

A

Hypoxanthine Guanine Phosphoribosyltransferase (HGPT) Deficiency

Severe gout, self-mutilation, and mental retardation

36
Q

[Pyrimidine Salvage]

What are the 2 mechanisms?

A
  1. Phosphoribosylation: Uracil + PRPP -> UMP
  2. Phosphorylation of free pyrimidine nucleosides

 Thymidine + ATP -> TMP + ADP
 Uracil + ribose -> Uridine + Pi
 Uridine + ATP -> UMP + ADP
 Cytidine + ATP -> CMP + ADP

37
Q

[Synthesis of Deoxyribonucleotides]

Starting product?

A

Diposphate Ribonucleosides (AMP, GDP, CDP, TDP)

38
Q

[Synthesis of Deoxyribonucleotides]

Function: Ribonucleotide Reductase

A

Reduces Ribonucleoside Diphosphate -> 2-Deoxyribonucleoside Diphosphate

39
Q

[Synthesis of Deoxyribonucleotides]

Function: Thioredoxin

A

Gets oxidized during deoxyribonucleotide formation

40
Q

[Synthesis of Thymidylate]

Function: Thymidylate Synthetase

A

Converts dUMP -> dTMP

Methyl group from reduction of Methylene-THF replaces H at C5

41
Q

Inhibitors of TMP Synthesis (2)

Mechanism

A

5-Fluoroacil -> FdUMP
- Competes with dUMP for the enzyme Thymidilate Synthetase, inhibiting dTMP formation

Methotrexate/Aminopterin

  • Stops Dihydrofolate (DHF) from being converted back to Tetrahydrofolate (THF)
  • dUMP cannot be converted to dTMP due to reduced amount of 1C carriers
42
Q

End product of Purines?

43
Q

[Gout]

Effect?

A

Hyperuricemia

Swelling of joints due to accumulation of Urate crystals that are insoluble

44
Q

[Gout]

What acts as an inhibitor to Xanthine and formation of Urate Crystals?

A

Allopurinol

45
Q

[Bubble Boy Disease / SCID]

What’s broken?

What caused it?

A

T Cell and B Cells

Defect in Adenosine Deaminase (AMP->IMP)
Accumulation of dATP which is the overall regulator for deoxyribonucleotide production

46
Q

[Pyrimidine Degradation]

Fates of Cytosine, Uracil and Thymine

A

Cytosine + Uracil -> b-Alanine

Thymine -> b-Aminobutyrate

47
Q

[Pyrimidine Degradation]

Nitrogen can be used as? (5)

A
  • Energy (e.g. creatinine)
  • Non-protein N-containing products (e.g.
    Nitrogenous bases, hormones, coenzymes)
  • Urea (to be excreted)
  • Uric acid
  • Glycine + Heme -> bilirubin
48
Q

[Nitrogen Balance]

Positive Balance when?

Negative Balance when?

A

Positive balance
 N input > N output
 During growth, pregnancy, lactation,
recovery from metabolic stress

Negative balance
N input < N output 
- Inadequate Dietary Protein
- Lack of essential amino acids
- Metabolic stress

[OS 201] 3rd Exam (10 decks)

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