Lect 9 Nucleotide Metabolism Flashcards Preview

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Flashcards in Lect 9 Nucleotide Metabolism Deck (33):
1

Nucleoside

Base + Sugar

2

Nucleotide

Base + Sugar + Phosphate

3

Purines

Pure As Gold (Ring)

Double Ring

Adenine & Guanine

Xanthine & Hypothanxine

4

Pyrimidine

CUt The Pye

Single Ring

Cytosine & Thymine

Uracil

5

What are 3 Roles of Nucleosides and Nucleotides

Components of Cofactors

Regulatory Roles

Important biomolecules

6

What is the overall Purine Nucelotide Synthesis process?

Sugar Molecule Synthesis ---> Ring Formation

7

What occurs in Purine synthesis Phase I?

What enzyme is used?

Ribose 5P Activation

Ribose 5P --> PRPP/Phosphoribosyl pyrophosphate 

(PRPP Synthetase)

8

Purine Phase II

What is the enzyme?

Why is this step special?

Convert PRPP to PRA (Phosphoribosylamine)

Glutamine Phosphoribosyl Pyrophosphate Amidotransferase (GPPA)

Rate Limiting Step

9

Purine Phase III

Why is methotrexate an inhibitor?

Why is it an anticancer drug?

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)

10

Purine Phase IV

Convert IMP to AMP and GMP

11

What are Sulfa Drugs and what are their importance?

Competitive inhibitors of bacterial enzyme incorporating PABA into folate

Dirsupts DNA replication selectivley in bacteria

12

Feeback Inhibition

Purine inhibition example

Accumulation of end product inhibit own synthesis

PRPP: inhibitted by IMP, AMP, GMP

 

13

Cross Regulation

Synthesis is stimulated by production of other substrate

AMP synthesis stimulated by GTP

GMP stimulated by ATP

14

Pyrimidine Nucleotide Synthesis Overall View

Pyrimidine Ring Formation --> Sugar Attachment

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

Cytosol and Mitochondria

15

What does Pyrimidine Synthesis Phase I consist of?

What is the rate limiting step?

Formation of the orotate ring --> Committed Step

Carbamoyl phosphate + Asp --> carbamoyl aspartate via aspartate transcarbamoylase

 

16

What does Pyrimidine Synthesis Phase II consist of?

What is orotic aciduria? and how is it treated?

Attach PRPP to Orotate Ring form UMP

Orotic Aciduria: Deficiency of UMP synthase

Tx: Oral Uridine

17

What occurs in Pyrimidine Synthesis Phase III?

What is 5-fluorouracil and what does it do?

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

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

18

What does Thymidine Kinase do?

What is the mechanism of Acyclovir (Antiviral)

What is it used for?

  • 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

Ribonucleases/Deoxyribonucleases Function

Convert RNA/DNA to short oligomers

20

Phosphodiesterases Function

Convert short oligomers to nucleotides or deoxynucleotides

21

Nucleotidases Function

Convert to nucleosides/deoxynucleosides

22

Nucleosidases Funcations

Removes ribose group to form Pyrimidines / Purines Rings

23

Purine Nucelotide Catabolism: GMP

Oxidative Process

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

24

Purine Nucelotide Catabolism: AMP

Oxidative Process

Allopurinol inhibits what enzyme? What steps does this affect?

AMP --> IMP --> Inosine

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

Xanthine Oxidase inhibited by Allopurinol

25

Adenosine Deaminase (ADA) is involved with what?

What do overproductions and deficiencies cause?

  • 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

What is GOUT

Where is it mostly affected?

Intense pain and inflammation in joints

Big toe most affected (metatarsal pharangeal joint)

 

27

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

Why does GOUT occur in extremities more often

When there is high concentration and at low temperatures

Lower temperature away from core

28

Pyrimidine Nucelotide Catabolism

Cytosine/Uracil

What is the fate of the final product?

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

FA Synthesis

29

Pyrimidine Nucleotide Catabolism

Thymine

What does B-aminoisobutyrate indicate?

What is the fate of the final products?

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

TCA Cycle

30

Purine Nucelotide Salvage Pathway

Adenine --> AMP

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

Renal Lithiasis (kidney stone) occurs with APRT defect

 

31

Purine Nucleotide Salvage Pathway

Guanine/Hypoxanthine --> GMP/IMP

What is caused by this defective enzyme?

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

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

32

Lesch Nyhan Syndrome

What does this cause?

Defect in HGPRT enzyme in purine salvage pathway

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

Urate kidney stones

33

Pyrimidine Nucelotide Salvage Pathway

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

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