Purine & Pyrimidine Flashcards Preview

Biochem Exam 3 > Purine & Pyrimidine > Flashcards

Flashcards in Purine & Pyrimidine Deck (54):
1

Nucleotide structure

Base + Pentose + p

2

Which type of base has 2 rings?

Purines

3

Which are the Purines?

A+G

4

Which are Pyrimidines?

C+U+T

5

Where is the OH attached on Ribose?

2' C

6

What can be salvaged?

Both Purines and Pyrimidines

Sugar+Base

7

Denovo synthesis takes place mainly where?

Brain and Liver

8

How do we build purines?

Start with R5P and build on the purine base

9

How do we build pyrimidines?

Synthesize with the pyrimidine ring then attach the R5P

10

Purine ring energy cost

6 ATP per nucleotide

11

How many N's in Purine ring?

4

12

Where does N1 come from on purine?

Aspartate

13

Where does N3 come from on Purine?

Glutamine

14

Where does N9 come from on Purine?

Glutamine

15

Where does N7 come from on Purine?

Glycine

16

Where to the Purine Carbons come from?

C2 and C8 from THF
C6 from Bicarb
C4 and C5 from Glycine

17

Purine Synthesis requires what substrate?

PRPP

18

What are the constituents of PRPP

R5P, ATP, Pyrophosphate

19

Committed step of Purine Synthesis?

Phosphoribosyl Amidotransferase (PRAT)

20

Purine Synthesis major intermediate

IMP

21

IMP synthesis Pathway?

(Glutamine+PRPP), Glycine, Formyl THF, Glutamine, CO2, Aspartate, Formyl THF

22

4 Regulated Reactions of Purine Synthesis (and what regulates them)

1. PRPP Synthase (-ADP/GDP)
2. PRAT (A & G Mono, Di, Triphosphates)
3. IMP DH (-GMP)
4. Adenylosuccinate Synthetase (-AMP)

23

Lesch Nyhan Syndrome Cause, Sx, Tx?

HGPRTase deficiency = No salvage pathway
Everything shunted to URIC ACID (via increased de novo synthesis)
Sx = Severe Neuro and Nephrolithiasis
Tx = Allopurinol (helps Nephro Sx but not CNS)

24

Purine Nucleoside Phosphorylase (PNP) ... What does it do, and what happens when you don't have it?

Normally takes inosine-> Hypoxanthine, Adenosine -> Adenine, and Guanosine -> Guanine. Basically converts nucleosides to free bases + Ribose-1P.

Nucleosides accumulate = Elevated dGTP = NO T-CELL function.

25

SCID cause, Effects,

Adenosine Deaminase deficiency.

Buildup of dATP. This is toxic to T cells, B cells, and NK cells.
Also inhibits SAM hydroxylase = reduced methylation rxns and accumulation of S-Adenosylhomocysteine (SAH)

26

Describe regulation in the Purine Salvage Pathway (3 ways is regulated or regulates stuff)

IMP/GMP inhibits HGPRTase
AMP inhibits APRTase

These also feed back to the de novo synthesis path enzymes (IMPDH and Adenylosucc. Synthetase)

PRPP is used in salvage, so it isn't available as a substrate for de novo.

27

Causes of Hyperuricemia and Gout

High PRPP Synthetase activity (R5P --> PRPP)
HGPRTase deficiency
VonGierkes

28

How the hell does VonGierke's result in hyperuricemia and gout anyway?

No Glucose 6 Phosphatase = Buildup of G6P, which gets shunted into the Pentose Phosphate Pathway. This results in increased R5P, which is a precursor to PRPP, resulting in increased denovo synthesis of purines and synthesis of uric acid.

29

Overall salvage pathway

AMP --> IMP --> HX ---> Xanthine Uric Acid ---> Urate

30

Link Between Fructose and gout?

Fructose metabolism = increased Fructose-6P

This drains the (P) pool, which lowers ATP available.

This results in increased Uric Acid.

31

Pyrimidine synthesis starts with

N base, then you add sugar and phosphate

32

Where do N's come from on Pyrimidine? C's?

Asp gives C4+5 and N1
Bicarb gives C2
Glutamine gives N3

33

Overall Pyrimidine Synthesis Reaction

Carbamoyl Phosphate --> N-CP --> Dihidroorotate --> Orotate --> OMP --> UMP

34

High orotate is indicative of what?
Why?

OTC defect in urea cycle

Orotate is a small base and can leak out cell

35

UMP synthase function? What happens when you are deficiency?

Dual function enzyme...
-Orotate phosphoribosyltransferase
-OMP decarboxylase
(takes Orotate --> OMP and OMP--> UMP)
Deficiency = HEREDITARY OROTIC ACIDURIA

36

Difference between NDP and NTP synthesis...

NDPs are made base-specific
NTPs are made with broad specificity

37

NDP synthesis (enzyme and reaction)

Adenylate Kinase and Guanylate Kinase
(=Nucleoside Monophosphate Kinases)

AMP + ATP --> 2ADP

38

NTP synthesis (enzyme and reaction)

Nucleoside Diphosphate Kinase

GDP + ATP ---> GTP + ADP
**intervonversion**

39

Deoxynucleotide Synthesis first 2 steps (including RLS)

make the ribonucleotide first, then deoxify!
RLS / 1st step = Ribonucleotide reductase (ex. ADP-->dADP)
2nd Step = Nucleoside-5-diphosphate kinase (ex. dADP --> dATP)

40

Weird stuff with dNT synthesis

dCDP --> dCTP
-OR-
dCMP --> dUMP via DEOXYCYTIDYLATE DEAMINASE

dUDP --> dUMP

dUMP (from either of the above)-->dTMP via THYMIDYLATE SYNTHASE

41

Effect of deoxyribonucleotides? When are they elevated?

Toxic! Normally only elevated in S-Phase

42

Ribonucleotide Reductase properties (4)

RLS for dNT synthesis
Requires THIOREDOXIN
2 sites: Activation and Specificity
ATP activates, dATP feedback inhibits

43

dTMP synthesis enzyme

Thymidylate synthase, needs N5N10 THF

44

N5N10THF is converted to ___ during dTMP synthesis?

Dihydrofolate

Regenerated by
(1) Dihydrofolate Reductase (-->THF)
(2) Hydroxymethyltransferase (N5N10)

45

Inhibitors of dihydrofolate reductase

Aminopterin and Methotrexate

46

The Thymidylate Synthase inhibitor that also inhibits dTMP synthesis is...

Fluorouracil

47

Fluorouracil function, use, and mechanism

Inhibits thymidylate synthase
Treatment for SOLID tumors
f-UTP is incorporated into RNA which inhibits Ribosome maturation

48

What is fdUMP? and what does it do?

Inhibitor of thymidylate synthase (via fluorouracil), keeps dUMP to incorporate into DNA, resulting in strand breakage.

49

Cytosine Arabinoside Mechanism and use

5' Triphosphate that incorporates into DNA and inhibits synthesis
Used for leukemia

50

What does methotrexate inhibit? why doesn't this work on all cells?

It inhibits Dihydrofolate Reductase (DHF-->THF)

Normal cells are rescued by N5-Formyl-THF (LEUCOROVIN, an analog that can be used similarly)

51

Hydroxyurea function and mechanism

Inhibits DNA synthesis (not RNA or protein)

Acts on Ribonucleotide reductase

52

Acyclovir and Gancyclovir properties, mechanism, uses

Purine analog that inhibits viral Thymidine Kinase (mammals can't use it)

In virus it is activated to monophosphate

Acyclovir for HSV, Gan for CMV retinitis

53

AZT properties and mechanism

Pyrimidine analog

Blocks HIV by inhibiting DNA

54

Fialuridine used for ___

Hep B