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MCM Exam 1 > Lect 9 Nucleotide Metabolism > Flashcards

Lect 9 Nucleotide Metabolism Flashcards

1
Q

Nucleoside

A

Base + Sugar

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2
Q

Nucleotide

A

Base + Sugar + Phosphate

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3
Q

Purines

A

Pure As Gold (Ring)

Double Ring

Adenine & Guanine

Xanthine & Hypothanxine

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4
Q

Pyrimidine

A

CUt The Pye

Single Ring

Cytosine & Thymine

Uracil

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5
Q

What are 3 Roles of Nucleosides and Nucleotides

A

Components of Cofactors

Regulatory Roles

Important biomolecules

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6
Q

What is the overall Purine Nucelotide Synthesis process?

A

Sugar Molecule Synthesis —> Ring Formation

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7
Q

What occurs in Purine synthesis Phase I?

What enzyme is used?

A

Ribose 5P Activation

Ribose 5P –> PRPP/Phosphoribosyl pyrophosphate

(PRPP Synthetase)

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8
Q

Purine Phase II

What is the enzyme?

Why is this step special?

A

Convert PRPP to PRA (Phosphoribosylamine)

Glutamine Phosphoribosyl Pyrophosphate Amidotransferase (GPPA)

Rate Limiting Step

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9
Q

Purine Phase III

Why is methotrexate an inhibitor?

Why is it an anticancer drug?

A

Construct IMP Ring (PRA –> IMP in 9 Steps)

Methotrexate inhibits (competitive) oxidation of NADPH by DHFR/Dihyrofolate Reductase

Methotrexate: Competitive Inhibitor of enzymes utilizing folate (disrupts DNA replication in rapidly dividing cell)

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10
Q

Purine Phase IV

A

Convert IMP to AMP and GMP

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11
Q

What are Sulfa Drugs and what are their importance?

A

Competitive inhibitors of bacterial enzyme incorporating PABA into folate

Dirsupts DNA replication selectivley in bacteria

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12
Q

Feeback Inhibition

Purine inhibition example

A

Accumulation of end product inhibit own synthesis

PRPP: inhibitted by IMP, AMP, GMP

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13
Q

Cross Regulation

A

Synthesis is stimulated by production of other substrate

AMP synthesis stimulated by GTP

GMP stimulated by ATP

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14
Q

Pyrimidine Nucleotide Synthesis Overall View

A

Pyrimidine Ring Formation –> Sugar Attachment

Sources: HCO3-, Gln, Asp, N, N-methylene THF

Cytosol and Mitochondria

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15
Q

What does Pyrimidine Synthesis Phase I consist of?

What is the rate limiting step?

A

Formation of the orotate ring –> Committed Step

Carbamoyl phosphate + Asp –> carbamoyl aspartate via aspartate transcarbamoylase

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16
Q

What does Pyrimidine Synthesis Phase II consist of?

What is orotic aciduria? and how is it treated?

A

Attach PRPP to Orotate Ring form UMP

Orotic Aciduria: Deficiency of UMP synthase

Tx: Oral Uridine

17
Q

What occurs in Pyrimidine Synthesis Phase III?

What is 5-fluorouracil and what does it do?

A

Convert UMP –> uridine, ctyosine, and thymidine (deoxy)nucelotides

(anticancer agent) inhibits thymidylate synthase (dUMP–>dTMP) and stops DNA production

18
Q

What does Thymidine Kinase do?

What is the mechanism of Acyclovir (Antiviral)

What is it used for?

A
  • Phosphorylates dT –> dTMP –> DNA
  • Acyclovir (resembles guanine) is phosphorylated by viral thymidine kinase
    • Convert to acyclo GMP –> aGTP –> DNA –> terminate DNA synthesis in infected cell
  • Chicken Pox and Herpes
19
Q

Ribonucleases/Deoxyribonucleases Function

A

Convert RNA/DNA to short oligomers

20
Q

Phosphodiesterases Function

A

Convert short oligomers to nucleotides or deoxynucleotides

21
Q

Nucleotidases Function

A

Convert to nucleosides/deoxynucleosides

22
Q

Nucleosidases Funcations

A

Removes ribose group to form Pyrimidines / Purines Rings

23
Q

Purine Nucelotide Catabolism: GMP

Oxidative Process

A

GMP –> Guanosine –> Guanine –> Xanthine –> Uric Acid (via xanthine oxidase)

24
Q

Purine Nucelotide Catabolism: AMP

Oxidative Process

Allopurinol inhibits what enzyme? What steps does this affect?

A

AMP –> IMP –> Inosine

AMP –> Adenosine –> Inosine (Adenosine Deaminase (ADA)) –> Hypoxanthine –> Xanthine (Xanthine Oxidase) –> Uric Acid (Xanthine Oxidase)

Xanthine Oxidase inhibited by Allopurinol

25
Q

Adenosine Deaminase (ADA) is involved with what?

What do overproductions and deficiencies cause?

A
  • Involved with Adenosine homeostasis
  • Overproduction ADA: Hemolytic anema (increased adenosine degradation –> premature RBC destruction)
  • Underproduction ADA: second most common form of severe combined immunodeficiency (SCID).
26
Q

What is GOUT

Where is it mostly affected?

A

Intense pain and inflammation in joints

Big toe most affected (metatarsal pharangeal joint)

27
Q

When do MSU (Monosodium Urate) crystals precipitate in joints?

Why does GOUT occur in extremities more often

A

When there is high concentration and at low temperatures

Lower temperature away from core

28
Q

Pyrimidine Nucelotide Catabolism

Cytosine/Uracil

What is the fate of the final product?

A

UTP/CTP –> Uridine –> Uracil –> B-alanine –> Maonyl CoA (water soluble)

FA Synthesis

29
Q

Pyrimidine Nucleotide Catabolism

Thymine

What does B-aminoisobutyrate indicate?

What is the fate of the final products?

A

Thymine –> B-aminoisobutryate (estimates DNA turnover) –> Methmalonyl CoA & Succinyl CoA (water soluble)

TCA Cycle

30
Q

Purine Nucelotide Salvage Pathway

Adenine –> AMP

A

Adenine + PRPP –> AMP via adenine phosphoribosyl transferase (APRT)

Renal Lithiasis (kidney stone) occurs with APRT defect

31
Q

Purine Nucleotide Salvage Pathway

Guanine/Hypoxanthine –> GMP/IMP

What is caused by this defective enzyme?

A

Guanine/Hpoxanthine + PRPP –> GMP / IMP (Hyoxanthine guanine phosphoribosyl transferase (HGPRT)

Lesch-Nyhan Syndrome & Kelly Seegmiller Syndrome occur with HGPRT defect

32
Q

Lesch Nyhan Syndrome

What does this cause?

A

Defect in HGPRT enzyme in purine salvage pathway

Overproduce uric acid –> Primary hyperuricemia and hyperuricosuria (leading to gout)

Urate kidney stones

33
Q

Pyrimidine Nucelotide Salvage Pathway

A

Uracil + Ribose –> Uridine –> UMP –> UDP –> UTP

Thymin + deoxyribose –> Deoxythymidine –> dTMP (thymidine kinase - acyclovir)–> dTDP –> dTTP

MCM Exam 1 (11 decks)

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