Biosynthesis Of Nucleotides

Front 1

What is the first MAJOR step in making Purins?

Back 1

Make IMP

Front 2

What is the committed step in making Purine synthesis?

Back 2

PRPP + Gln ---------> 5-phosphoribosylamine during IMP formation

-amidophosphoribosyl transferase

Front 3

What enzyme makes 5-phosphoribosylamine?

Back 3

amidophosphoribosyl transferase

Front 4

What are the essential building blocks to make IMP

Back 4

1) gly (2)
2) gly
3) asp
4) N10-formyl THF (2)

Front 5

What is the function of glutamine in purine biosynthesis?

Back 5

transfers amino group onto sugar at 1C

Front 6

what is the function of N10-formyl THF?

Back 6

1 carbon donor

Front 7

Where does PRPP come from?

Back 7

Pentose Phosphate Pathway

Front 8

What is the 2nd MAJOR step in making purines?

Back 8

Make AMP and GMP

Front 9

nucleic acids can form H-bonds in what structures?

Back 9

1) RNA/DNA (complementary NAs)
2) ATP/GTP (energy carriers)
3) NADP+/NAD+ (electron carriers)

Front 10

Purines are synthesizes as what structures?

Back 10

Nucleotides (base + sugar + p)

Front 11

What sugar are purines built on?

Back 11

ribose-5-phosphate

Front 12

What building blocks are needed to convert IMP to AMP?

Back 12

1) GTP
2) Asp (n-donor)

Front 13

How many TOTAL aspartates are used to make AMP from PRPP?

Back 13

2

Front 14

What building blocks are needed to convert IMP to GMP?

Back 14

1) NAD+
2) ATP
3) Gln (n-donor)

Front 15

How many TOTAL glutamines are used to make GMP from PRPP?

Back 15

3

Front 16

How many TOTAL glutamines are used to make AMP from PRPP?

Back 16

2

Front 17

What is the purpose of recycling purines?

Back 17

1) save energy and time
2) regulate the amount of AMP and GMP we have

Front 18

What are the 2 ways we can recycle purines?

Back 18

1) convert AMP and GMP back to IMP
2) convert nucleotides back to R5P and bases

Front 19

What are purines degraded to for excretion?

Back 19

Uric acid

Front 20

What are the steps from Guanine to Uric Acid?

Back 20

Guanine ---> Xanthine ---> Uric Acid

Front 21

What are the steps from Adenine to Uric Acid?

Back 21

1) Adenine->AMP->IMP
2) IMP->hypoxanthine->xanthine-> uric acid

Front 22

What enzyme catalyzes both of the reactions below:

hypoxanthine ---> xanthine ----> uric acid

Back 22

xanthine oxidase

Front 23

Is uric acid soluble?

Back 23

not at high conc.

Front 24

What is the role of:

hypoxanthine-guanine phosphoribosyl transferase?

Back 24

converts Guanine and Hypoxanthine back GMP and IMP

Front 25

What is gout?

Back 25

Inflammatory arthritis caused by elevated uric acid conc. in the blood and buildup up uric acid crystals in joints and kidney.

Front 26

What causes gout?

Back 26

the underexcretion and overproduction of uric acid/urate.

Front 27

Describe the gout spiral

Back 27

1) uric acid crystals form in joints (UA is a foreign body)
2) Inflammatory response -> WBCs attack joint tissue
3) proteins lower pH, causing further crystal formation and more inflammation.

Front 28

What are the 3 steps to managing gout?

Back 28

1) reduce uric acid/urate levels
2) break down existing irate
3) reduce inflammation

Front 29

Function of allopurinol and oxipurinol:

Back 29

blocks urate formation by inhibiting Xanthine Oxidase

create soluble Allantoin, which is excreted

Front 30

Function of uricase?

Back 30

break down irate

Front 31

function of probenecid?

Back 31

increase irate excretion

Front 32

function of NSAIDs, steroids, and colchicine?

Back 32

reduce inflammation

Front 33

Describe Lesch-Nyhan Syndrome?

Back 33

An x-linked, recessive, defect in purine recycling pathway.

CAUSE:
deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) which inhibits the purine salvage pathway.

LEADS TO:
1) inc. urate production (no salvage pathway)
2) unused PRPP

SYMPTOMS:
1) severe gout,
2) self mutitlation and mental retardation
3) Spasticity (muscle stiffness)
4) hyperuricemia and hyperuricosuria

Front 34

What drugs can we use to treat Lesch-Nyhan Syndrome?

Back 34

1) allopurinol to alleviate hyperuricemia
2) antiinflammatories

Front 35

What is the salvage pathway rxn?

Back 35

PRPP + Pur -------> purine monophosphate

Front 36

What enzymes are used in the purine salvage pathway?

Back 36

1) APRT (adenine phosphoribosyl transferase)
2) HGPRT (hypoxanthine-guanine phosphoribosyl transferase)

Front 37

What is the function of APRT?

Back 37

transfers a phosphoribosyl from PRPP to adenine

Front 38

What is the function of HGPRT?

Back 38

transfers a phosphoribosyl from PRPP to guanine or hypoxanthine.

Front 39

What is the reasoning behind blocking purine synthesis for infection/chemotherapy control?

Back 39

-both involve cells that need purines for RNA/DNA synthesis during mitosis.
-suppressing purine synthesis inhibits mitosis

Front 40

What drugs are used to inhibit purine synthesis?

Back 40

1) Azaserine
2) Azathioprine
3) Mycophenolate
4) Methotrexate

Front 41

Function of Azaserine

Back 41

Gln analogue (Gln amidotransferase inhibitor)

- no Gln metabolism -> purine synthesis blocked

Front 42

Function of Azathioprine

Back 42

Gln analogue (Gln amidotransferase inhibitor)

- no Gln metabolism -> purine synthesis blocked

Front 43

Function of Mycophenolate

Back 43

IMP dehydrogenase inhibitor
-no purine synthesis

Front 44

Function of Methotrexate

Back 44

Blocks folic acid production (B9) -> 1C donor
-INDIRECTLY blocks purine synthesis

Front 45

In what form are Pyrimidines synthesized?

Back 45

free bases

-later transfered to R5P

Front 46

Where are purines synthesized?

Back 46

cytosol

Front 47

Where are pyrimidines synthesized?

Back 47

cytosol and mitochondria

Front 48

What is the first MAJOR step in pyrimidine synthesis?

Back 48

Make UMP

Front 49

What is the committed step in pyrimidine synthesis?

Back 49

Gln + 2ATP + HCO3- + H2O ---> Carbamoyl-P +Ortho-P
-like in urea cycle

Front 50

What enzyme do we use to make carbamoyl phosphate from glutamine?

Back 50

Carbamoyl phosphate synthetase

Front 51

What are the essential building blocks in UMP synthesis?

Back 51

1) Asp
2) Gln
3) Bicarbonate
4) Ubiquinone

Front 52

Where do we get R5P?

Back 52

PPP

Front 53

Which pyrimidine biosynthesis reaction occurs in mitochondria?

Back 53

Dihydroororate ----> ororate

Front 54

Which step in pyrimidine biosynthesis uses ubiquinone?

Back 54

Dihydroororate ----> ororate

Front 55

What drugs inhibit the conversion of Dihydroororate to prorate in immune cells?

Back 55

Leflunomide

Front 56

Function of Leflunomide?

Back 56

suppresses inflammation of rheumatoid and psoriatic arthritis by inhibit the conversion of Dihydroororate to prorate in immune cells.

Front 57

What is the 2nd MAJOR step in pyridine synthesis?

Back 57

making CTP and TTP

Front 58

What are the essential building blocks in making CTP from UMP?

Back 58

1) Gln

Front 59

What are the essential building blocks in making TTP from UMP?

Back 59

1) dUMP (from UMP)
2) N5,N10-methylene THF (1C methyl groups)

Front 60

Why is the UMP->TTP pathway more complicated than UMP->CMP?

Back 60

because Thyamine is only used for DNA so belong in separate pools.

Front 61

what molecules are needed to converts dUMP to TMP?

Back 61

1) N5,N10-methylene THF (methyl donor)
2) thymidylate synthase

Front 62

what reactions regenerate N5,N10-methylene THF?

Back 62

dihydrofolate--->THF--->N5,N10-methylene THF

Front 63

what enzyme regenerate N5,N10-methylene THF?

Back 63

dihidrofolate reductase

Front 64

what enzyme converts N5,N10-methylene THF to dihydrofolate?

Back 64

thymidylate synthase

Front 65

what building blocks are required to regenerate N5,N10-methylene THF?

Back 65

1) NADPH
2) serine (for -OH) b/w THF--> N5,N10-methylene THF

Front 66

cancer drugs target which molecule in PYRIMIDINE SYNTHESIS?

Back 66

dihydrofolate reductase

Front 67

what are the cancer drugs that inhibit PYRIMIDINE SYNTHESIS?

Back 67

1) methotrexate
2) aminopterin

-act on dihydrofolate reductase

Front 68

what inhibits thymidylate synthase?

Back 68

F-dUMP

Front 69

which metabolic pathway creates NADPH?

Back 69

PPP

Front 70

why is the PPP important in the formation of nucleotides?

Back 70

source of NADPH

Front 71

what reaction makes dNDPs from NDPs (except for TTP)?

Back 71

NDP + NADPH ---> dNDP + NADP+

Front 72

what enzyme catalyzes dNDP formation (except TTP)?

Back 72

ribonucleotide reductase

Front 73

what protein converts UDP to dUDP?

Back 73

thioredoxin

Front 74

what enzyme converts UDP to dUDP?

Back 74

ribonucleotide reductase

Front 75

what enzyme regenerates reduced thioredoxin?

Back 75

thioredoxin reductase

Front 76

what cofactor acts on thioredoxin reductase

Back 76

NADPH

Front 77

function of ribonucleotide reductase?

Back 77

converse NDP to dNDP

Front 78

can cytosine directly enter the pyramiding recycling pathway?

Back 78

no, must be converted to uracil first.

Front 79

what is produced in converting Uracil to Urea?

Back 79

B-ureidoproprionate, B-alanine, NH4+, and CO2

Front 80

what is produced in converting Thymine to Urea?

Back 80

B-ureidoproprionate, NH4+, and CO2

Front 81

what cofactor is used in pyrimidine recycling?

Back 81

NADPH