Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

SFM (Scientific Foundations of Medicine) > Lecture 8: Nucleotide Metabolism > Flashcards

Lecture 8: Nucleotide Metabolism Flashcards

1
Q

What is the difference between nucleosides and nucleotides, and what is a deoxyribonucleotide?

A

nucleosides: nitrogenous base + sugar
nucleotides: nitrogenous base + sugar + phosphate

deoxyribonucleotide: -H at 2’ C of sugar ring
ribonucleotide: -OH at 2’ C of sugar ring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are specific roles of nucleotides and nucleosides?

A

nucleotides: cAMP and cGMP –> regulatory roles, stabilizing regulatory elements (m7GTP cap at 5’ end of eukaryotic mRNA)
nucleosides: in important biomolecules (adenosine in vitamin B12)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the difference between de novo synthesis of purine formation vs salvage pathway?

A

de novo: base formed on ribose 5-phosphate (liver, cytosol)

salvage: ribose-5-phosphate added to preformed base (organelles)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the difference between de novo synthesis of pyrimidine formation vs salvage pathway?

A

de novo: pyrimidine ring followed by ribose phosphate

salvage: pyrimidine nucleotides from pyrimidine bases in RNA/DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the 4 phases of purine synthesis?

A
  1. activation of ribose-5-phosphate
  2. conversion of PRPP into phosphoribosylamine
  3. construction of IMP branch point purine ring
  4. conversion of IMP into adenosine and guanosine (deoxy) nucleotides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Purine Synth Phase I

A
  • ribose-5-phosphate (PPP) –> PRPP
    enzyme: PRPP synthetase
  • (+): phosphate (allosterically); lvls signal cellular activity (ATP consumption)
  • (-): purine nucleotides (GMP, AMP, IMP)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Purine Synth Phase II

A
  • PRPP –> phosphoribosylamine (PRA)
    enzyme: glutamine:phosphoribonyl pyrophosphate aminotransferase (amino group from glutamine @ C’1)
  • (+): PRPP
  • (-): GMP, AMP, IMP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the committed step of Purine Synthesis?

A

conversion of PRPP into phosphoribosylamine via glutamine:phosphoribosyl pyrophosphate amidotransferase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Purine Synth Phase III

A
  • construction of IMP (9 step ring constructing seq)
  • IMP is branch point in anabolism of purines

Methotrexate BLOCKS this process from happening (anticancer drug)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Purine Synth Phase IV

A
  1. IMP –> AMP (adenylosuccinate synthetase)
    • (-): AMP
    • REPLENISH fumarate (TCA cycle)
  2. IMP –> XMP (NAD–>NADH) –> GMP
    • IMP dehydrogenase ((-): GMP)
    • GMP synthetase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the three phases of pyrimidine synthesis?

A
  1. fabrication of pyrimidine ring as OROTATE
  2. orotate attach to PRPP, generating uridine monophosphate
  3. uridine monophosphate into cytosine and thymidine nucleotides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Pyrimidine Synth Phase I and Urea Cycle defect

A

fabrication of pyrimidine ring as OROTATE

  • carbamoyl phosphate synthetase
    (+): PRPP
    (-): UTP
  • defect in urea cycle = inc. carbamoyl phosphate lvls = Hyperammonemia and Orotic Aciduria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the Rate Limiting Step of Pyrimidine Synthesis?

A

formation of carbamoyl phosphate

Gln –> carbamoyl phosophate –> carbamoyl aspartate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Pyrimidine Synth Phase II

A

attachment of orotate to PRPP = UMP

UMP synthetase attaches orotate to PRPP, then decarboxylates OMP –> UMP (BIFUNCTIONAL)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is Orotic Aciduria, where does it occur, and how is it treated?

A
  • inability to convert orotic acid to UMP
  • megaloblastic anemia (mental/physical development delays)
  • treatment: oral uridine
  • occurs in defect of UMP Synthase in Phase II of Pyrimidine Synth
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Pyrimidine Synth Phase III

A
  • UMP converted to cytosine and thymidine
    cytosine: UTP –> CTP –> dCTP (amination)

thymidine: UMP –> dUDP –> dTTP
- dihydrofolate generation
- thymidylate inhibited by 5-fluorouracil

(dUDP loop used to keep dUTP lvls low so it doesnt get incorporated into DNA)

17
Q

What are the two key regulatory steps of Pyrimidine Synthesis?

A
  1. Carbamoyl phosphate synthetase
    (+): PRPP
    (-): UMP/UTP
  2. Aspartate transcarbamoylase (ATCase)
    (-): CTP
18
Q

What is the importance of the Pentose Phosphate Pathway?

A
  • produces ribose-5-phosphate and NADPH
  • NADPH: reducing environments for glutathione (key antioxidant) –> keeps it from gunking up

liver is principle site of purine/pyrimidine synthesis

19
Q

What is the importance of Methotrexate?

A
  • cancer treatment
  • targets dihydrofolate reductase (DFHR) –> normally converts dietary folate to tetrahydrofolate (binds to it 100x more tightly)
  • prevents NADPH oxidation
  • disrupts cancer DNA replication
20
Q

What is the importance of “sulfa” drugs?

A
  • antibacterial agent that competitively inhibits bacterial enzyme incorporating PABA into folate
  • DISRUPTS DNA REPLICATION IN BACTERIA
21
Q

What happens when you deprive cells of GMP and dGTP?

A
  • targeting IMP dehydrogenase
  • immunosuppressant disrupting B/T cell DNA rep.
  • deprives them of dGTP, helping to prevent rejection
22
Q

What happens in Purine catabolism?

A
  • ribose removed from guanosine = guanine
  • AMP converted to inosine (remove ribose) = hypoxathine
  • both create xanthine –> uric acid (GOUT)
23
Q

Deficiencies in Purine Catabolism (2)

A
  1. adenosine deaminase (ADA)
    • irreversible deamination (adenosine to inosine)
    • overprod: hemolytic anemia
    • underprod: SCID
  2. xanthine oxidase
    • leads to uric acid (Gout)
    • acid hydrogen, limited water solubility
24
Q

Severe Combined Immunodeficiency (SCID)

A
  • genetic disorder that compromises B/T cells
  • “Bubble Boys” –> need to be isolated from environ.
  • ADA deficiency (2nd most common) leads to high levels of adenosine –> dADP/dATP
  • this inhibits formation of other dNDPs (impairs DNA synthesis)
25
Q

What is Gout and how can it be treated?

A
  • high levels of uric acid in blood

Primary and Secondary hyperuricemia

  • painful sodium urate deposits in joints (kidneys)
  • treatment: allopurinol (inhib xanthine oxidase)
  • diet purine diet, alcohol, meat, seafood trigger
26
Q

Primary vs Secondary Hyperuricemia

A 
Primary = overproduction of uric acid
Secondary = underproduction of uric acid
27
Q

What does Pyrimidine Catabolism produce?

A
  • converts to ketogenic/glucogenic, water-soluble compounds

uracil/cytosine –> malonyl CoA (ketogenic)

thymine –> methylmalony CoA or succinyl CoA (glucogenic)

28
Q

Purine Salvage

A

APRT –> adenine to AMP

HGPRT –> guanine/hypoxanthine to GMP/IMP

29
Q

Lesch-Nyhan Syndrome

A
  • defects in HGPRT (purine salvage), rare form of primary hyperuricemia
  • hyperuricemia leads to gout, urate kidney stone, poor muscle control, mental retardation (synth at 200x normal), tendency for self-mutilation
  • HGPRT activity <1.5% normal = severe neurological problems, choreoathetosis, self-destructive biting
30
Q

Kelley-Seegmiller Syndrome

A
  • HGPRT deficiency (>8% normal activity)

- results in Gout, kidney destruction without neurological symptoms

31
Q

Acyclovir

A
  • antiviral agent that far exceeds viral thymidine kinase phosphorylation (convert to monophosphate dGMP)
  • acyclo-dGTP incorporated into rapidly dividing viral cells (terminates DNA replication (no 3’-OH) –> blocks DNA polymerase
  • chickenpox, shingles, HPV sore

SFM (Scientific Foundations of Medicine) (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions