Biochem Nucleotide Metabolism

Front 1

what is SCIDs?

Back 1

severe combined immunodeficiency syndrome

Front 2

what vitamin intermediates are important in nucleotide synthesis?

Back 2

folate intermediates

Front 3

for what is amino acid metabolism important?

Back 3

nucleotide synthesis

Front 4

what is PRPP synthetase?

Back 4

phosphoribosyl pyrophosphate synthetase

Front 5

why is de novo synthesis of nucleotides not incredibly important?

Back 5

body is very good at scavenging used nucleotides

Front 6

what is the rate-limiting enzyme in nucleotide synthesis?

Back 6

PRPP amidotransferase

Front 7

what is the allosteric activator for PRPP amidotransferase?

Back 7

PRPP

Front 8

what is the result of the interrelationship between purine metabolism and carbohydrate metabolism?

Back 8

excess purine metabolism results in excess uric acid (gout)

Front 9

how are adenine and guanine synthesis regulated?

Back 9

reciprocally

(need adenine to produce guanine, and need guanine to produce adenine)

Front 10

what are the two regulation mechanisms of PRPP amidotransferase?

Back 10

feedforward activation via PRPP
feedback inhibition by end products (AMP/GMP)

Front 11

where is the purine nucleotide cycle most important? why?

Back 11

skeletal muscle

in fasting and starvation conditions, skeletal muscle degrades nucleotides (in addition to AAs), and the purine nucleotide cycle provides an anapleurotic intermediate for TCA cycle from amino acid aspartate

Front 12

in the purine nucleotide cycle, what happens to the amino acid aspartate?

Back 12

converted to fumarate

Front 13

in the purine nucleotide cycle, what are the intermediates?

Back 13

AMP -> IMP -> Adenylosuccinate -> AMP

(taking up aspartate and releasing fumarate - aspartate minus nitrogen)

Front 14

what is the end product of all purine catabolism?

Back 14

uric acid

Front 15

where is the first part of body to usually display symptoms of gout?

Back 15

big toe

uric acid precipitates in synovial joints

Front 16

what is the definition of gout?

Back 16

hyperuricemia

concentration of uric acid in blood gets high and urate crystals form

Front 17

what is allopurinol?

Back 17

nucleotide analog inhibitor of xanthine oxidase, commony used to treat gout

Front 18

what are the major purine nucleotides?

Back 18

adenosine
guanosine

Front 19

what are the intermediate purine nucleotides?

Back 19

inosine
xanthosine

Front 20

what enzyme has a defect in SCIDs?

Back 20

adenosine deaminase (ADA)

Front 21

what enzymes are inhibited pharmacologically to treat gout?

Back 21

xanthine oxidase

Front 22

in SCIDS, what nucleotides have an effect on DNA synthesis, and therefore proliferation?

Back 22

deoxyadenosine

Front 23

what is the critically important salvage enzyme involved in guanine salvage?

Back 23

hypoxanthine-guanine phosphoribosyl transferase (HGPRT)

Front 24

how does dATP have an effect on proliferation?

Back 24

strongly inhibits ribonucleotide reductase, inhibiting synthesis of deoxyribonucleotides, so that DNA cannot be synthesized and cells can't proliferate

Front 25

what is the direct, critically important function of HGPRT?

Back 25

add sugar to guanine

Front 26

what is the indirect, critically important function of HGPRT?

Back 26

forming IMP from hypoxanthine

Front 27

what causes Lesch-Nyhan syndrome?

Back 27

total loss of HGPRT

Front 28

what are the symptoms of Lesch-Nyhan syndrome?

Back 28

hypotonia
spasticity
self-mutilation (including biting off lips and fingertips)
early death

Front 29

what causes Kelley-Seegmiller syndrome?

Back 29

reduced HGPRT activity

Front 30

what are the causes of gout?

Back 30

PRPP synthetase defect
PRPP amidotransferase defect
HGPRT defect

Front 31

what are the symptoms of Kelley-Seegmiller syndrome?

Back 31

gout

Front 32

how does HGPRT deficiency cause gout?

Back 32

guanine and xanthine are not salvaged by HGPRT, so they are driven into excess uric acid (causes gout)

Front 33

what is the clinical definition of gout?

Back 33

sodium urate precipitate in joints

Front 34

what two tests are used to diagnose gout?

Back 34

serum urate
creatinine clearance

Front 35

intake of what should be reduced in gout patients?

Back 35

purine rich foods (red meat)
EtOH consumption
caffeine
diuretics
nicotinic acid
cisplatin

Front 36

for what is nicotinic acid used?

Back 36

treat hypercholesterolemia

Front 37

for what is cisplatin used?

Back 37

cancer chemotherapeutic

Front 38

what are the symptoms of tumor lysis syndrome?

Back 38

hyperkalemia (high K)
hyperphosphatemia (high P)
hypercalcemia (high Ca)
high purine content in blood

Front 39

what can cause tumor lysis syndrome?

Back 39

chemotherapy of hematologic cancers

Front 40

with what is the pain of gout treated?

Back 40

NSAIDs

Front 41

what is probenecid?

Back 41

drug often used in gout

inhibits reabsorption of urate in proximal tubule
increases effectiveness of other drugs by preventing loss in urine

Front 42

from what are purines and pyrimidines formed?

Back 42

amino acids

Front 43

how is purine biosynthesis different from pyrimidine biosynthesis?

Back 43

the purine nucleobase is built first and then the sugar is added
the pyrimidine nucleobase is built onto the structure of the sugar

Front 44

what is the function of CPS2?

Back 44

catalyze the synthesis of carbamoyl phosphate in the cytosol

Front 45

what are the differences between CPS I and CPS II?

Back 45

CPS1 - acquires N from free ammonia; regulated by N-acetylglutamate

CPS2 - acquires N from glutamine; not regulated

Front 46

carbamoyl phosphate synthetase II is a part of what complex?

Back 46

aspartate transcarbamylase (ATCase)

Front 47

what nucleotide is present in only RNA? DNA?

Back 47

uridine in RNA
thymine in DNA

Front 48

what is the function of nucleoside phosphate kinases?

Back 48

phosphorylate monophosphorylated and diphosphorylated nucleosides to give the diphosphorylated and triphosphorylated products respectively

Front 49

what is the function of CTP synthetase?

Back 49

interconverts UTP and CTP

Front 50

what is the function of thymidylate synthase?

Back 50

generate thymidine monophosphate (must be dTMP because there are no rTMP) for use in DNA synthesis and repair

Front 51

what is the effect of inhibiting thymidylate synthase?

Back 51

stops cells from growing (as in several chemotherapeutics)

Front 52

what is the only enzyme to use a folate analog and create dihydrofolate rather than tetrahydrofolate?

Back 52

thymidylate synthase

Front 53

what enzyme is absolutely essential for DNA synthesis? why?

Back 53

dihydrofolate reductase

it refills the supply of THF (from DHF) and subsequently N5,N10-methyleneTHF which are necessary for DNA synthesis

Front 54

what does methotrexate do?

Back 54

inhibits dihydrofolate reductase (DHFR), which inhibits the proliferation of cells (e.g. tumor cells)

Front 55

why is methotrexate no longer used to treat cancer? what is it used to treat?

Back 55

effect of methotrexate is to add DHFR repeats on genes

when a dose works to inhibit tumor, it reappears later, and dose must be increased to be effective

Front 56

how is thymidylate synthase a target for chemotherapy?

Back 56

5-fluorouracil
5-fluorodeoxyuridine
both converted to fluorodeoxyuridine monophosphate (FdUMP)

FdUMP is a UMP analog that suicide inhibits thymidylate synthase

Front 57

what two drugs inhibit DHFR?

Back 57

methotrexate (was cancer chemo, now psoriasis)
trimethroprim (antimicrobial - was TB treatment)

Front 58

what are the important features of pyrimidine catabolism?

Back 58

get non-toxic intermediates
converted to TCA cycle intermediates

Front 59

what causes Orotic Aciduria?

Back 59

Type I - OMP decarboxylase and orotate phosphoribosyl transferase defects

Type II - OMP decarboxylase defect

Front 60

what are the symptoms of orotic aciduria?

Back 60

retarded growth
severe anemia

Front 61

what is used as the phosphate donor for NMP kinases?

Back 61

ATP

Front 62

what is the function of NMP kinases?

Back 62

convert nucleotide monophosphates to nucleotide diphosphates

Front 63

what reaction is catalyzed by adenylate kinase?

Back 63

2ADP -> AMP + ATP

Front 64

what reaction is catalyzed by NDP kinases?

Back 64

N1TP + N2DP <-> N1DP + N2TP

Front 65

what is used as the phosphate donor for NDP kinases?

Back 65

ATP or GTP (no substrate specificity)

Front 66

what is the function of ribonucleotide reductase (RR)?

Back 66

convert nucleotide diphosphates into deoxynucleotide diphosphates by reducing 2' hydroxyl

(won't work on nucleotide monophosphates)

Front 67

how is glutathione involved in deoxyribonucleotide biosynthesis?

Back 67

involved in part of the regulation of ribonucleotide reductase

through a series of S-S bond formations and cleavages