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Flashcards in Nucleotide Metabolism Deck (62):
1

What are critical functions of nucleotides

1. storage and flow of genetic info: key structural comp on DNA and RNA
2. storage and source of energy: energy rich phosphodiester bonds in ATP & GTP
3. Component of key cofactors: NAD, FAD, coenzyme A, S- adensoylmethionine
4. form activated intermediates: UDP glucose in glycogen synthesis, CDP= diacylglycerol in phospholipid synthesis
5. Metabolic regulators: cAMP, cGMP are cellular second messengers.

2

What are three principal components nucleotides have

1. nitrogenous base
2. pentose sugar
3. one/more phosphate groups

3

what are the two types of nitrogenous bases

1. pyrimidine (little structure)
2. purine (big structure)
(nitrogen and carbon in ring)

4

What include the pyrimidines

1. Cytosine
2. Thymine
3. Uracil
"cut the pyramid"

5

what are the purines

1. adenine
2. guanine
"Pure As Gold"

6

what are the pentose sugars

1. ribose (OH is on the bottom)
2. deoxyribose (just H on the bottom)

7

What are nucleosides formed by

attachment of nitrogenous base to sugar. Attachment is always to C-1 on sugar, N-9 of purine, ad N-1 of pyrimidine

8

How are nucleotides formed

by attachment of phosphate to sugar in nucleoside. Phosphates are never attached to base. Phosphates can be added to sugar.

9

adenine + sugar =
when it has all three component =

adenose; adenylate

10

What are two types of pathways of nucleotides

1. De novo (from new): synthesis from metabolic precursors (aa, ribose - 5- phosphate, CO2, NH3) Energy expensive!
2. salvage: recycle free bases and nucleosides released from nucleic acid breakdown. Energy economical! Do this a lot with purines!

11

which methyl group is primarily used

tetrahydrafolate

12

What

Build oratate first then attach it.

13

What are the precursors for purines and pyrimidines

inosine 5- monophosphate and orotidine 5' monophosphate

14

Synthesis of common nucleotides DOES NOT proceed via their free bases: precursor is always coupled to:

ribose

15

5 phosphoribosyl-1 pyrophosphate (PRPP) is a key activated ____ intermediate which activates C1 on ribose. It is a key substrate in both purine and pyrimidine synthesis

sugar

16

The purine ring precursor ____ (a nitrogenous base) is synthesized stepwise directly on the ribose C-1

hypoxanthine

17

The pyrimidine ring precursor ____ is synthesized stepwise THEN attached to the ribose C-1.

orotate

18

where do you get ribose 5 - phosphate from

PPP; pentose phosphate pathway

19

How are purines synthesized

1. assemble 5 member ring on C-1 of PRPP
2. complete 6 member ring

20

what aa are used to make purines

1. 2 glutamine
2. 1 glycine
3. 1 aspartate
4. 2 formate from tetrahydroflate
5. 1 CO2- from bicarbonate

21

The nucleotide is called ____. The base is called ____

inosinate (IMP) -the base, phosphate and sugar; hypoxanthine.

22

You can convert inosinate to

Can convert it to AMP or GMP by adding nitrogen groups to two spots

23

How do you make the 5 membered ring

1. Directly attach the N group of glutamine
2. Add 2 glycine (C--C-N)
3. Add 2 C via formate
5. Add C02 from bicarbonate
5. Add N from aspartate and then close the ring

24

what is the committed step

adding first N group on PRPP via glutamine PRPP amidotransferase

25

what is glutamine PRPP admidotransferase inhibited by

azaerine, acivian. This is a good target for chemotherapy

26

How many ATP are made from making inosinate

7 ATP

27

AMP uses ___as the N donor. GMP uses _____ as N donor.

aspartate; glutamine

28

Inosinate in ____

tRNA

29

How is purine regulated

almost exclusively via feed back inhibition of
1. PRPP synthetase by end products
2. committed step by end products
3. branches by each end product
4. reciprocal use of GTP and ATP in AMP, GMP pathways

30

How do you make pyrimidines

glutamine + bicarbonate to make carbamoyl phosphate
then add aspartate to make orotate and hook it up to PRPP. (making ring first and then adding it to the sugar) The first ring we're making is UMP.
* this can happen in cytosol

31

How many ATPs does it take to make pyrimidine

2

32

what makes a pyrimidine

1. glutamine
2. 1 aspartate
3. 1 CO2
4. 2 ATP

33

where does pyramdine synthesis get N from

directly from glutamine

34

what is the committed step in making pyrymidines. what is it feedback inhibited by?

aspartate transcarbamoylase. Inhibited by CTP

35

Common nucleotides already have ____added. PRPP is key to both purine and pyrmidine synthesis.

sugar

36

What happens after you have UMP?

UTP --> animate it to CTP (by using glutamine as a N group donor)

37

Nucleoside monophosphate kinase uses ATP as source of phosphate and:

we can swap phosphate groups among all of our bases.

38

what enzyme gives you deoxyribonucleotides

ribonucleotide reductase; makes internal disulfide bond. Donates H and e- from enzyme to form disulfide bond.

39

Process of re reducing requires

glutathione (GSH) and NADPH

40

How can thymidine (dTMP) can be synthesized

From deoxy precursors:
1. CDP -->deoxy CDP -->deaminated dUTP --> dUMP-->dTMP
2. UDP-->dUDP-->dUTP -->dUMP--> dTMP

41

what enzyme is precursor for thymidine synthesis

dUMP

42

what enzyme converts dUMP to dTMP

thymidylate synthase

43

what is thymidylate synthase a good target for

chemotherapy; if you cant make T to go into DNA; DNA synthesis will slow down

44

what is a good agent for chemotherapy or what inhibits thymidylate synthase

flourouracil

45

what is difference bet dTMP and dUMP

methyl group; it

46

what donates a methyl group to make TMP

N10 tetrahydrofolate; it has to be regenerated.

47

what converts dihydrofolate to tetrahydrofolate

dihydrofolate reductase

48

what is dihydrofolate reducatase a good target for

chemotheraupetic agents and some classes of antibiotics.

49

what is dihydrofolate reductase inhibited by

methotrexate, aminopterin, & trimethoprim

50

what are breakdown products of pyrimidine

free ammonia (goes to urea) and succinate (goes to TCA cycle); so we mainly say breakdown product is UREA

51

what is breakdown product of purines

URATE; a lot recycled in salvage pathway

52

what enzyme is used to make purine, adenine via the salvage pathway

adenosine phosphoribosyltransferase (APRT)

53

what enzyme is used to make purine, guanine

HGPRT

54

What is the nucleotide catabolism for purines like

takes N group back off and forms inosine--> take sugar off and maky hypothanxine --> xanthine--> urate

55

What does SCID stand for

severe combined immuno deficient; complete lack of immune system; there is a deficiency in adenosine deaminada (ADA). T and B lymphocytes do not dev properly

56

what converts hypoxanthine to xanthine

xanthine oxidase; generating peroxide in our body.

57

what converts adenosine to inosine

adenosine deaminase

58

too much uric acid:

starts to precipitate and can cause gout. Therefore We inhibit enzymes: adenosime deaminase, & xanthine oxidase with inhibitor drugs

59

whats gout

heritable leading to elev uric acid in blood; can cause damage to kidneys

60

which mechanisms can lead to elevated serum urate:

1. Hyperactive PRPP synthetase:excess PRPP accelerates purine biosynthesis

2. Partial lack of HGPRT: reduced salvage pathway; leads to excess PRPP, and accelerated purine biosynthesis

61

how do you treat gout

allopurinol; enters salvage pathway and forms ribonucleotide; uses up PRPP which reduces purine biosynthesis. Other drugs include probenecid and febuxostat

62

what is Lesch-Nyhan Syndrome

complete genetic lack of HGPRT; X linked recessive (males) manifests early; mental retardation, poor coordination, self destructive, self mutilating, gout