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Flashcards in Nucleotide Metabolism Deck (56)
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1

base + sugar

nucleoside

2

base + sugar + phosphate

nucleotide

3

enzymes required for synthesis of purines are located where?

cytoplasm

4

What is the first step in de novo purine synthesis?

Ribose-5-Phosphate + ATP >>5-phosphoribosyl-1-pyrophosphate (PRPP)
Enzyme: PRPP synthetase
**ribose-5-phosphate comes from PPP

5

What is the committed step of de novo purine synthesis?

PRPP + Glutamine>>PRA (5-phosphoribosylamine)
Enzyme: amidophosphoribosyltransferase

6

In regards to the synthesis of purine, where do the carbons and nitrogens come from?

Carbon is from CO2
Nitrogen is from glycine, glutamine, and aspartate

7

In regards to the synthesis of purine, what is the donor of one-carbon group?

N10-formyl THF (requires B12)

8

How many molecules of ATP is needed to make IMP?

5

9

What is the precursor to AMP and GMP?

IMP

10

What is the first purine to be made in de novo purine synthesis?

IMP

11

What is the rate-limiting step in the synthesis of GMP? What is it inhibited by?

Enzyme: IMP dehydrogenase
Inhibited by: GMP (end product inhibition)

12

What is the rate-limiting step in the synthesis of AMP? What is it inhibited by?

Enzyme: adenylsuccinate synthetase
Inhibited by AMP (end product inhibition)

13

Summarize the route for the synthesis of GTP starting with IMP.

IMP>>XMP>>GMP>>GDP>>GTP

14

Summarize the route for the synthesis of ATP starting with IMP.

IMP>>adenylosuccinate>>AMP>>ADP>>ATP

15

Describe how to form ADP from AMP.

nucleoside monophosphate kinase, takes phosphate group from ATP and transfers it to AMP to make ADP
AMP + ATP >> ADP + ADP

16

What regulates PRPP synthtase?

feedback inhibition by ADP and GDP

17

What regulates the committed step of purine synthesis?

Enzyme: amidophosphoribosyltransferase
- allosterically regulated by its substrate PRPP
(this enzyme has two binding sites for PRPP)
- inhibited by AMP and GMP

18

GMP degradation

GMP>>Guanine>>Xanthine

19

AMP degradation

AMP>>inosine>>hypoxanthine>>xanthine

20

What are the two ways that AMP can be degraded to inosine?

2- step process
1) AMP deaminase, 5'-nucleotidase
2) 5'-nucleotidase, Adenosine deaminase

21

Both AMP and GMP degradation converge at xanthine, what happens after that?

xanthine is converted to uric acid by xanthine oxidase.
uric acid is excreted in urine

22

What reactions do xanthine oxidase catalyze?

1) hypoxanthine>>xanthine
2) xanthine>>uric acid

23

What is this condition called?
Reduced excretion of uric acid:
- renal insufficiency
- metabolic acidosis
Increased production of uric acid
- increased nucleotide turnover (hemolytic diseases, chemotherapy)
- diets rich in purine
**alcohol consumption results in both situation

hyperuricemia

24

What is this condition called?
- uric acid is relatively insoluble
- increased uric acid >> crystals of sodium urate deposits in joints of extremities

gout

25

What is this condition called?
- uric acid leads to uric acid stones in kidneys

uric acid urolithiasis (kidney stones due to uric acid)

26

What is an effective treatment for hyperuricemia?
- stops production of uric acid
- hypoxanthine and xanthine are excreted instead
- converted to its active form by xanthine oxidase, which then in turn inhibit it

Allopurinol>>oxypurinol by xanthine oxidase
- inhibits xanthine oxidase

27

What is the first pyrimidine nucleotide synthesized?

UMP

28

Main differences between synthesis of purines and pyrimidines

purines: ring is synthesized on the sugar
pyrimidines: ring is synthesized separately then sugar gets attached

29

Steps 1-3 of UMP synthesis are catalyzed by this enzyme

CAD (Carbamoyl phosphate synthetase II, Aspartate transcarbamoylase, Dihydroorotase)

30

Steps 4-5 of UMP synthesis are catalyzed by this enzyme

UMP synthase (Orotate phosphoribosyltransferase, OMP decarboxylase)