Ch 41 Purine And Pyr Metabolism

Front 1

what kind of disease is gout?

Back 1

hyperuricemia, acute athritis, accumulation of urate crystals

Front 2

medication for gout?

Back 2

allopurinol (Zyloprim)

Front 3

what is Lesch-Nyhan syndrome?

Back 3

hyperuricemia, neurologic problems, motor disability, failure to hold up head, SELF INJUROUS behavior striking feature

Front 4

what is Lesch-Nyhan syndrome resembled to?

Back 4

cerebral palsy

Front 5

metabolic fcns of purine and pyrimidne nucleotdies/

Back 5

atp energy, dna and rna components, second messengers(cAMP), coenzyme(NAD, CoA), allosteric effectors (ATP, AMP)

Front 6

what are processes requiring rapid DNA and RNA synthesis?

Back 6

embryogenesis, hemaptopoiesis-(RBC, lymphocytes), rapidly regenerating tissues, tumor cell growth

Front 7

what is a nucleoside?

Back 7

N base and sugar

Front 8

nucleotide

Back 8

N base and sugar and phosphate

Front 9

purine base-nucleoside-nucleotide of adenine

Back 9

adenine-adenosine--AMP

Front 10

purine base-nucleoside-nucleotide of guanine

Back 10

guanine→guanosine→GMP

Front 11

purine base - nucleoside-nucleotide of hypoxanthine

Back 11

hypoxanthine→ inosine→ IMP

Front 12

purine base-nucleoside-nucleotide of xanthine

Back 12

xanthine → xanthosine → XMP

Front 13

purine bases?

Back 13

uric acid, adenine, guanine, hypoxanthine, xanthine

Front 14

typesof pyrimidine?

Back 14

uracil, thymine, cytosine, orotic acid

Front 15

pyrimidine bases - nucleoside - nucleotide of uracil

Back 15

uracil→uridine→UMP

Front 16

pyrimidine bases - nucleoside - nucleotide of thymine

Back 16

embryogenesis, hemaptopoiesis-(RBC, lymphocytes), rapidly regenerating tissues, tumor cell growth

Front 17

pyrimidine bases - nucleoside - nucleotide of cytosine

Back 17

cytosine → cytidine → CMP

Front 18

pyrimidine bases - nucleoside - nucleotide of orotic acid

Back 18

orotic acid → orotidine → OMP

Front 19

how does body get ribonucleotides?

Back 19

de novo synthesis, purines, nucleoside

Front 20

enzymes in nucleotide metabolism

Back 20

ribonucleotide reductase, kinase, polymerase, nuclease, nucleotidase, phosphorylase

Front 21

ex of ribonucleotide reductase

Back 21

NDPs→ dNDP

Front 22

ex of kinase

Back 22

NMP+ ATP→ NDP+ ATP→ NTP

Front 23

ex of polymerase

Back 23

NTP→RNA, dNTP→DNA

Front 24

ex of nuclease

Back 24

RNA→ribonucleotide, DNA→deoxyribonucleotides

Front 25

ex of nucleotidase

Back 25

NTP+H20→ NDP+H20→ NMP+Pi

Front 26

ex of phosphorylase

Back 26

nucleosides→purine base + ribose 1 P

Front 27

structure of purine ring--number C, N

Back 27

N 1,3,7,9 C 2,4,5,6,7

Front 28

where do C2,8 get C from in purines?

Back 28

tetrahydrofolate-C2,8

Front 29

where does C6 get C from in purines?

Back 29

CO2

Front 30

where do C4, C5, N7 get atoms from in purines?

Back 30

glycine

Front 31

where do N3,9 get N from in purines?

Back 31

glutamine

Front 32

where does N1 come from in purines?

Back 32

aspartic acid

Front 33

what is the first regulated step of de novo synthesis of purine nucleotides?

Back 33

formation of PRPP from ribose 5 phosphate (scaffold) upon which purine ring is built

Front 34

what is the enzyme of the first regualted step of de novo synthesis of purine nucleotides?

Back 34

PRPP synthetase

Front 35

what inhibits the first regulated step of de novo synthesis of purine nucleotides?

Back 35

ADP, GDP, other nucleotdies

Front 36

what is fate of PRPP?

Back 36

purine nucleotides, pyrimidine nucleotides, NAD, NADP

Front 37

what is the committed step of de novo synthesis of purine nucleotides?

Back 37

formation of 5 Phosphoribosylamine (PRA)-first nucleotide from PRPP with glutamine

Front 38

what is the enzyme of the committed step of de novo synthesis of purine nucleotides?

Back 38

PRA synthase or PRPP amidotransferase

Front 39

what inhibits the committed step of de novo synthesis of purine nucleotides?

Back 39

AMP, GMP, IMP

Front 40

what activates the committed step of de novo synthesis of purine nucleotides?

Back 40

PRPP synthetase

Front 41

what happens when AMP plus IMP or GMP is added into committed step?

Back 41

total blockage of PRA synthase activity

Front 42

fate of PRA?

Back 42

IMP

Front 43

significance of IMP?

Back 43

branch point for forming both AMP and GMP

Front 44

how is GMP formed from IMP?

Back 44

IMP→ XMP + glutamine + ATP → glutamine

Front 45

enzymes involved in GMP formation from IMP?

Back 45

IMP dehydrogenase, GMP synthase

Front 46

how is AMP formed from IMP?

Back 46

IMP+ asparate + GTP→ adenylosuccinate→ AMP + fumarate

Front 47

enzymes involved in AMP formation from IMP?

Back 47

adenylosuccinate synthetase, adenylosuccinase

Front 48

what inhibitsIMP from forming into XMP→GMP→GDP→GTP

Back 48

GMP, later ATP

Front 49

what inhibits IMP from forming into adenylosuccinate → AMP→ADP→ATP?

Back 49

AMP, GTP

Front 50

how is hyperuricemia caused?

Back 50

superactive PRPP synthetase, excess PRPP broken down to uric acid

Front 51

how is adenine salvaged to produce purines? What enzyme involved?

Back 51

APRT(transferase) adds PRPP, forms AMP

Front 52

how is hypoxanthine salvaged to produce purines? What enzyme involved?

Back 52

HGPRT adds PRPP, forms AMP

Front 53

how is guanine salvaged to produce purines? What enzyme involved?

Back 53

HGPRT adds PRPP, forms AMP

Front 54

fcn of HGPRT and APRT?

Back 54

operate similar mechanism to recapture hypoxanthine, guanine, and adenine

Front 55

what disease lacks HGPRT?

Back 55

lesch-nyhan x-linked syndrome

Front 56

significance of PRPP?

Back 56

precursor for de novo synthesis, reactant for salvage

Front 57

degradation of adenine nucleotides lead to

Back 57

hypoxanthine→xanthine→uric acid via xanthine oxidase

Front 58

degradation of guanine nucleotides lead to

Back 58

xanthine→ uric acid via xanthine oxidase

Front 59

pathway of GMP degradtion?

Back 59

GMP→guanosine→(phosphorylase) guanine→xanthine→uric acid

Front 60

pathway of AMP degradtion?

Back 60

AMP→IMP→inosine→hypoxanthine→xanthine→uric acid

Front 61

what is allopurinol?

Back 61

drug used to treat hyperuricemia

Front 62

fcn of allopurinol?

Back 62

inhibits xanthine oxidase, controls production of uric acid. Increases IMP, GMP, decrease PRPP, resotres regulation of de novo purine synthesis

Front 63

causes of hyperuricemia?

Back 63

overactive de novo synthesis, lack of reutilization

Front 64

what causes accelerated de novo purine sytnhesis?

Back 64

increased intracellular nonpurine precursors, ex PRPP, ribose 5 P

Front 65

cuase of decreased reutilization? Leads to?

Back 65

lack of HGPRT. Leads to increased PRPP, dec salvaged purine nucleotides(IMP,AMP,GMP). Accelerates do novo synthesis, more uric acid

Front 66

what does deficiency in purine nucleotide phosphorylase and adenosinedeaminase result in?

Back 66

increased guanosine, adenosine leads to immunodefiecny disease. Toxic to B cells, T cells

Front 67

what are the sources of C and N in pyrmidine nucleotide structure?

Back 67

glutamine, aspartic acid, CO2

Front 68

what part of the pyrimidine structure does glutamine provide?

Back 68

N3

Front 69

what part of the pyrimidine structure does CO2 provide?

Back 69

C2

Front 70

what part of the pyrimidine structure does aspartic acid provide?

Back 70

C4,5,6, N1

Front 71

what is the regulated step in formation of pyrimidine structures(OMP then UMP? Enzyme?

Back 71

glutamine + CO2+ ATP→ carbomoyl phosphate via CPS II

Front 72

what inhibits the regualted step in pyrimidine formation?

Back 72

UTP, CTP

Front 73

what goes into the formation of pyrimidine? What does it start with and end up with?

Back 73

carbamoyl phospahte→NAD+, PRPP added, CO2 leaves→UDP→UTP→CTP

Front 74

what enzyme is involved in formation of CTP? Reactant? Product?

Back 74

UTP+ glutamine+ ATP→ CTP via CTP synthase

Front 75

what activates CTP formation?

Back 75

GTP

Front 76

what are pyrimidine nucleotides degraded into?

Back 76

CO2 + H20

Front 77

what enzymes are targeted in cancer chemotherapy in nucleotide metabolism?

Back 77

ribonucleotide reductase, thymidylate synthase, dihydrofolate reductase

Front 78

fcn of ribonucleotide reductase?

Back 78

reduces ribose to deoxyribose.

Front 79

substrate of ribonucleotide reducatase? Significance?

Back 79

thioredoxin. Uses NADPH from pentose phosphate pathway

Front 80

what inactivates ribonucleotide reductase?

Back 80

radical scavengers, ex. Hydroxyurea.

Front 81

what acts as a master regulator of RR?

Back 81

dATP

Front 82

fcn of thymidylate synthase?

Back 82

transfers 1 C from methylene FH4 to dUMP to form dTMP. Oxidizes tetrahydrofolate

Front 83

what is 5 fluorouracil?

Back 83

inactivates thymidylate synthase, blocks cell division

Front 84

what is methotrexate?

Back 84

inactivates dihydrofolate reductase, blocks re-reduction of hydrofolate

Front 85

what is rescue therapy?

Back 85

aggressive form of cancer therapy, blocks ALL cell division in body

Front 86

what enzyme is used in rescue therapy?

Back 86

N5 formyl tetrahydrofolate, reactivates enzymes