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Biochem Block 3 > Nucleotide Metabolism > Flashcards

Flashcards in Nucleotide Metabolism Deck (43):
1

Nucleotide functions

1. Structural component of DNA AND RNA
2. Carriers of activated intermediates (UDP-glucose)
3. Structural components of coenzymes used in metabolism
4. Secondary messengers in signal transduction (cAMP)
5. Energy (ATP)
6. Regulate pathways (using energy)

2

Structure of nucleotides

Nitrogenous base
Sugar

3

Purines

-dicyclic
-adenine and guanine

4

Pyrimidines

-monocyclic
-cytosine, thymine(DNA) and uracil(RNA)

5

Sugar is nucleotides

RNA:ribose
DNA: deoxyribose

6

Why is DNA more stab,e than RNA?

DAN uses deoxyribose which lacks an oxygen so it is more stable

7

Difference between nucleotides and nucleoside

Nucleoside: nitrogenous base and sugar
Nucleotides: nucleoside plus a phosphate group

8

What provides the energy to drive these reaction So?

-anhydride bond links 2 and 3 phosphate on nucleotides
-high energy bond that drives biochemical reactions
-ATP AND GTP

9

Where does the ribose 5p come from for purine synthesis?

HMP shunt

10

What is a key difference in purine and pyramides metabolism?

Purines directly build the nitrogenous base ONTO the sugar
-pyramides build the base then attach it to the sugar

11

PRPP synthase in purine metabolism

-catalyze so formation of the activated pentose
-uses energy

12

Regulation of PRPP SYNTHASE

Activator: inorganic phosphate
Inhibitor: purine ribonucleotides

13

What is the default of purine nucleotides synthesis?

-produces ribonucleotides(not deoxyribose

14

What is the rate limiting step of purine synthesis?

PRPP amidotransferase

15

PRPP AMIDOTRANSFERASE REGULATION

Activated: PRPP (substrate)
Inhibitors: purine nucleotides(end products)

16

What does folate do?

-required for subsequent steps as a carbon donor
-active form is THF

17

What enzyme makes THF

-dihydrofolate reductase turns folate into THF

18

Who makes their own folate?

-bacteria make their own folate, we cant.

19

What does THF turn into?

-THF acts as a carbon donor and makes IMP
-IMP can then turn into AMP and GMP

20

6-Mercaptopurine

-purine analog that acts as a product inhibitor
-inhibits PRPP amidotransferase
-if base is formed, it will have mutations

21

Methotrexate

-folic acid analog
-inhibits digydrofolate reductase so no THF can be made
-works ONLY IN MAMMALS
-selectively inhibits rapidly dividing cells

22

Sulfonamides

-structural analog of para-aminobenzoic acid (PABA)
-competitive inhibitor of bacteria producing folic acid
-bacteria purine synthesis inhibited

23

What is the rate limiting enzyme for pyrimidine synthesis?

-CPS II

24

Regulators of CPS II

-activated by PRPP
-Inhibited by UTP(end product)

25

What are the two amino acids used in nitrogenous base structure of pyrimidines?

-glutamine and aspartate

26

What does PRPP provide for pyrimidine synthesis?

-pentose

27

ribonucleotide reductase

-ribonucleotides are converted into deoxyribonucleotides
-hydroxyurea inhibits it

28

Hydroxyurea

-inhibits ribonucleotide reductase
-also treats sickle cell by promoting fetal hemoglobin

29

convert dUMP into dTMP

-use thymidylate synthase

30

5-FU

-anti tumor drug that inhibits thymidylate synthase

31

what do 5-FU and hydroxyurea target?

-affect production of DNA, but not RNA
-so really good at targeting rapidly dividing cells

32

Trimethoprim

-antibiotic that is selective for the prokaryotic version of dihydrofolate reductase

33

Pyrimidine breakdown

-they are not salvaged to a significant degree
-no high yield disease from breakdown so not important

34

Why is it important to recycle purines?

-purine bases are more complex than pyrimimdines
-take more steps to make it
-salvaging it is more important because it takes too much energy to make them

35

salvage pathway of purine general

-base is recovered by removing phosphate and sugar moieties
-this yields hypoxanthine or guanine
-those are shuttled back into synthesis

36

adenosine deaminase deficiency

-causes SCID
-immune system(T and B cells) are primarily affected
-patients are super susceptible to inflection (bubble)
-it cannot be recycled, so youre excreting too much

37

treatment of SCID

-bone marrow transplant or enzyme replacement

38

Xanthine oxidase

-excretion pathway of purines
-produces uric acid which is then excreted as urine

39

Gout

-result of hyperuricemia
-accummulation of uric acid crystals in the joints
-gouty arthritis

40

What causes gout?

-overproduction of uric acid
-problem with excretion

41

Allopurinol

-inhibits xanthine oxidase
-helps overproducers of uric acid stop making it

42

Lesch-Nyhan syndrome

-X linked
-deficiency in purine salvage pathway
-defect in HGPRT
-you end up excreting like 90%
-extreme hyperuricemia

43

Gout and eyeballs

-deposits of tophi in cornea, iris, sclera, lens
-formation of transparent vesicles(metalic)
-bleeding in subjunctiva