Purine and Pyrimidine Metabolism Flashcards Preview

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Flashcards in Purine and Pyrimidine Metabolism Deck (44):
1

Purines, their nucleosides, and their nucleotide forms

Adenine
Adenosine
Adenosine X Phosphate (ATP, AMP, etc)

Guanine
Guanosine
Guanosine X phosphate (GMP, etc)

Hypoxanthine
Inosine
IMP

Xanthine
Xanthosine
XMP

2

Pyrimidines, their nucleosides, and their nucleotide forms

Cytosine
Cytodine
CMP

Thymine
Thymidine
TMP

Uracil
Uradine
UMP

3

Digestion of RNA/DNA

first step

DNA/RNA is broken into oligomers by

RNA: Ribonuclease
DNA: Deoxynuclease

4

Digestion of RNA/DNA

second step

Oligomers are separated into individual nucleotides by phosphodiesterase

5

Digestion of RNA/DNA

third step

phospho-ester bond is broke by nucleotidase

6

Digestion of RNA/DNA

fourth step

the base is removed from the sugar by nucleosidase

7

Rinonucleases/Deoxyribonucleases do what

convert RNA and DNA to short oligomers

8

Phosphodiesterases

convert these oligomers to nucleotide monophosphases (NMPs) or deoxynucleoside monophosphates (dNMPs)

9

Catabolism of GMP to Uric acid

GMP --> Guansosine ---> Guanine --> Xanthine --> Uric acid

10

Catabolism of AMP to Uric acid

AMP -breaks down in two ways

1. AMP--- (adenosine monophosphate deaminase) --> IMP --> Inosine --> hypoxanthine -- (xanthine oxidase)---> xanthine --(xanthine oxidase) --> uric acid

2. AMP --> Adenosine --> (adenosine deaminase) --> inosine --> hypoxanthine ---(xanthine oxidase)--> xanthine --uric acid

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adenosine deaminase (ADA)

excessive production of ADA leads to hemolytic anaemia
underproduction of ADA lead to SCID

12

SCID

severe combined immune deficiency
defective T/B cells
second worst form caused by underproduction of ADA
X-linked: only impacts boys

deficiency of ADA leads to overproduction dATP, which blocks synthesis of dNDP/dNTPs.

impaired DNA synthesis and compromised immune system


13

Overproduction of adenosine deaminase (ADA) leads to

over-degradation of adenosine: depletes adenine nucleotide pool and triggers premature destruction of RBCs

14

Drug target for gout and drug

allopurinal targets xanthine oxidase

15

Xanthine oxidase

catalyzes oxidation of hyoxanthine to xanthine and xanthine to uric acid


has 2 FADs, 2 Mo atoms, and 8 Fe atoms per molecule of enzyme

16

Gout (general)

intensely painful/inflamed joints

most commonly affected area is big toe. (metatarsal pharangeal joint)

historically regarded as disease of the wealthy (too much wine, food, and sex)

17

Gour (details): primary, secondary

overproduction of uric acid = primary hyperuricemia
underexcretion of uric acid = secondary hyperuricemia

sodium-urate crystals build up in synovial fluid
MOs consume them, trigger acute inflammatory response

18

hyperuricemia

plasma levels of uric acid exceed ability to dissolve them

19

What causes gout?

diet rich in purinesL MEAT and SEAFOOD, (beans, lentils, asparagus, spinach)

20

gout =

excess purines

21

treatments of gout (6)

NSAIDs
steroids
urate oxidase
allopurinol
colchicine
probenecid

22

colchicine

decreases granulocyte movement to site of affected area

23

allopurinol

inhibits xanthine oxidase to form more soluble hypoxanthine

24

probeneceid

increases excretion of uric acid

25

serum uric levels
urinary uric levels
level indicating risk for gout

4-9 mg/dl men
3-6 mg/dl in women
26 mg/hr in urine

ABOVE 9 mg/dl increased risk of gout

26

Pyrimidine catabolism: UMP, UDP, UTP

1) [UMP/DP/TP+dUMP/dDP/dTP]----nucleotidase----> Uridine/deoxyuridine --> Uridine/Deoxyuridine --> --> uracil --> melonyl Coa (ketogenic)

27

Pyrimidine catabolism: CMP/DP/TP+dCMP/dCDP/dCTP

CMP/DP/TP+dCMP/DP/TP ----> neuclotidase --> Cytodine/Dcytodine --> deaminase rxn --> Uradine/deoxyuradine --> Uracil --> melonyl Co A

28

Pyrimidine catabolism; deoxythymidine

dTDP/TTP --> nucleotidase --> Thymine --> Succinyl CoA
MethylMalonyl CoA

29

which pyrimidines are converted to ketogenic compounds and what are they

Uracil and Cytosine

Melonyl co A

30

which pyrimidines are converted to glucogenic compounds and what are they

thymine

succinyl co-a and methylmelonyl co a

31

the "end" products of pyrimidine catabolism are insoluble or soluble?

water soluble

32

Pyrimidine synthesis: committed step

committed step is the synthesis of phosphoribosyl amine

33

phosphoribosyl amine =

first committed step in purine synthesis

this compound is either hypoxanthine ribose or

INOSINE MONOPHOSPHATE

34

INOSINE MONOPHOSPHATE

the phosphoribosyl amine indicating the first committed step in purine synthesis

also called hypoxanthine ribose phosphate

inosine is the nucleoside of hypoxanthine (its base)

35

Fate of inosine monophosphate

not used in DNA, so it is converted into adenosine and guanosine monophosphate

36

Two salvage enzymes responsible for converting inosine monophosphate to AMP and GMP

first has four words in it.
second has 3 words in it

1) hypoxanthine guanine phosphoribosyl transferase
2) adenine phosphoribosyl transferase

37

Purine synthesis: raw substrate molecules

CO2, Asp, Gln, Gly N-5, N-10-formyl THF

THF is the important one to remember

38

Pyrimidine synthesis: raw substrate molecules

HCO3, Gln, Asp, N-5, N-10 methylene TH

THF, again, the important one

39

THF

tetrahydrafolate

40

PRPP

MUST be remembered

41

the two essential substrates used in purines and pyrimidines (both)

THF and PRPP

42

Purine vs Pyrimidine synthesis de novo: first step

unique because purine syn. begins with ribose and build ring structures on it

pyrimidines build ring structures and build on ribose

43

De novo synthesis of purines: first step

PRPP synthase adds phosphate to ribose carbon 1 (From ATP) to make PRPP (ribose with two Ps)

inorganic phosphate is +FB
GMP, AMP, IMP are -FB

44

De novo synthesis of purines: second step

d