Nucleotide Metabolism

Question 1

Nucleotides are structural components of ___ and ___

Answer 1

DNA and RNA

Question 2

Nucleotides are carriers of activated intermediates

Answer 2

UDP-glucose in glycogen formation

Question 3

Nucleotides are structural components of several coenzymes…for ex:

Answer 3

CoA
NAD+
FAD
NADP+

Question 4

Secondary messengers in signal transduction, such as

Answer 4

cAMP and cGMP

Question 5

Energy currency of the cell, in the form as:

Answer 5

ATP

Question 6

Nucleotides act as regulators of many pathways, like:

Answer 6

ATP or AMP activating or inhibiting a pathway

Question 7

Summary of Nucleotide functions

Answer 7

Structural component (DNA RNA CoA FAD NADP+ and NADP+)
Carriers of activated intermediates (UDP-glucose)
Secondary messengers in signal transduction (cAMP and cGMP)
Energy currency of the cell (ATP)
Regulators of many pathways (ATP/AMP being an inhibitors/activator)

Question 8

Features of the structure of Nucleotides

Answer 8

Nitrogenous base and sugar

Question 9

Purines

Answer 9

Adenine

Guanine

Question 10

Pyrimidine

Answer 10

Cytosine

Thymine(DNA)/Uracil(RNA)

Question 11

Nucleotides as a sugar

Answer 11

Ribose in RNA and Deoxyribose as DNA

Question 12

Nucleoside

Answer 12

Nitrogenous Base + Sugar

Question 13

Nucleotide

Answer 13

Nucleoside + 1-3 phosphate groups

Question 14

What part of nucleotides drive many biochemical reactions?

Answer 14

The anhydride bonds linking the 2nd and 3rd phosphate groups

Question 15

Purine Nucleotide Synthesis

Answer 15

• Ribose-5-P is from HMP Shunt
• PRPP synthetase catalyzes the formation of the activated Pentose (Phosphoribosyl-pyrophosphate)
• Nitrogenous base is attached at the 1’ carbon, where the pyrophosphate was attached
• DNA/RNA is created

Question 16

What does the default purine nucleotide synthesis do?

Answer 16

Produce ribonucleotides

If deoxyribonucleotides are needed, furthers steps are taken

Question 17

Rate limiting step of Purine Synthesis

Answer 17

-Via PRPP Amidotransferase (regulated, committed step)

Inhibited by: purine nucleotides (end products)

Activated by: PRPP (substrate)

Question 18

_________________ is required to make THF, which does what?

Answer 18

Dihydrofolate reductase

Creates Tetrahydrofolate, the form in which FOLATE is used as a CARBON DONOR

Question 19

_______________ is a purine anaglog, which does what?

Answer 19

6-mercaptopurine.

Inhibits PRPP Amidotransferase (similar to high levels of natural purine inhibition)

Question 20

What is Methotroxate?

Answer 20

A folic acid analog, an anti-tumor drug.

Inhibits DIHYDROFOLATE REDUCTASE

• inhibiting nucleotide biosynthesis
• inhibiting rapidly dividing cells selectively

(Works specifically in mammalian cells)

Question 21

Sulfonamides and Purine Synthesis

Answer 21

Structural analogs of PABA (para-aminobenzoic acid)

Competitive inhibit of bacterial production of folic acid

Bacterial purine synthesis inhibited

Humans do not rely on folic acid synthesis and are unaffected

Question 22

Sulfa drugs function as:

Answer 22

Antibiotics

Question 23

What is the rate limiting step of Pyrimidine Nucleotide Synthesis?

Answer 23

CPSII, carbamoyl phosphate synthetase II

Activated by: PRPP

Inhibited by: UTP (end product)

Question 24

CPS-1 is the rate limiting step of:

Answer 24

Urea cycle

Question 25

Pyrimidine synthesis key points

Answer 25

2 AAs become part of nitrogenous base structure of pyrimidines (GLUTAMINE and ASPARTATE) PRPP provides the Pentose for the Pyrimidine

Question 26

Ribonucleotides can be converted into deoxyribonucleotides by:

Answer 26

Ribonucleotide reductase

Question 27

___________ is an anti-tumor drug that inhibits ribonucleotide reductase

Answer 27

Hydroxyurea

Question 28

Hydroxyurea functions

Answer 28

used to treat sickle cell anemia, but not related to its use as an anti-tumor drug Increases the synthesis of fetal hemoglobin that can alleviate the effects of sickle cell hemoglobin

Question 29

dTMP is used in:

Answer 29

Deoxyribonucleotides

Question 30

_____________ is used in conversion from dUMP to dTMP, used in production of nucleic acids

Answer 30

Thymidylate synthase

Question 31

What inhibits thymidylate synthase? And therefore inhibits production of nucleic acids

Answer 31

5-FU, or 5-fluorouracil

Question 32

What 2 drugs affect the production of DNA, but not RNA?

Answer 32

Hydroxyurea and 5-FU

Question 33

A class of antibiotic that is selective for the prokaryotic version of dihydrofolate reductase

Answer 33

Trimethoprim

Question 34

Humans require ______ in the diet, while prokaryotes produce their own.

Answer 34

Folate

Question 35

An additional class of antibiotics that target enzymes in bacteria that make their own folic acid

Answer 35

Sulfonamides Humans don't have these enzymes Selectively toxic to prokaryotes Inhibit nucleotide metabolism

Question 36

Nucleotide metabolism

Answer 36

Pyrimidines are not salvaged to a significant degree No high yield disease or enzymes are associated with their breakdown or salvage, so that pathway will not be discussed

Question 37

Why are purine bases more complex to synthesize than pyrimidines?

Answer 37

Purines are dicyclic, more steps involved, and salvage pathway is more critical.

Question 38

Salvage pathway of Purines

Answer 38

Nitrogenous base is recovered after removing phosphate and sugar moieties which yield HYPOXANTHINE or GUANINE, that can be shuttled back into purine nucleotide synthesis

Question 39

Adenosine deaminase deficiency

Answer 39

One of the causes of Severe Combined Immunodeficiency Disease (SCID) T-cells and B-cells are particularly affected Causes patients to be susceptible to almost any microorganism Requires pt to be a bubble boy, lol

Question 40

Treatment for SCID

Answer 40

Bone marrow transplant, or enzyme replacement Target for gene therapy trial

Question 41

During nucleotide metabolism, the base can be shuttled back into purine synthesis or:

Answer 41

Degraded to uric acid Uses the intermediate xanthine, and xanthine oxidase Excreted in urine GOUT

Question 42

Gout is the result of:

Answer 42

Hyperuricemia Accumulation of uric acid crystals in the joints Leading to inflammation and gouty arthritis

Question 43

Gout is caused by:

Answer 43

Under excretion/overproduction of uric acid (most common) Poor kidney function, acid-base imbalance, certain drugs

Question 44

In the overproducers of uric acid patients, or gout patients, what drug is used?

Answer 44

Allopurinol inhibits xanthine oxidase, which produces uric acid

Question 45

Lesch-Nyhan syndrome

Answer 45

Xlinked Deficiency in the purine salvage pathway Caused by defect in HGPRT Deficit of purines

Question 46

HGPRT deficiency

Answer 46

Blockage of the pathway forces the purine degradation products into the production of uric acid

Question 47

Lesch-Nyhan Syndrome symptoms

Answer 47

Severe mental retardation Self-destructive behavior, self-mutilation

Question 48

Gout can affect the eye by deposits of _____ in various locations

Answer 48

Tophi

Question 49

Tophi, side affect of gout, can be deposited in:

Answer 49

``` Conjunctiva Cornea Iris Sclera Lens ``` Formation of transparent vesicles Bleeding in subconjunctival space and vascular changes

Question 50

Functional roles of nucleotides and central role in storage of genetic information

Answer 50

DNA, RNA, ATP, AMP, cAMP, cGMP, CoA, FAD, NAD+, NADP+

Question 51

Distinguish between riconucleic acids and deoxyribonucleic acids

Answer 51

Ribose has an alcohol group on C2, deoxyribose has H on C2

Question 52

Ribose-5-P is obtained from:

Answer 52

HMP shunt

Question 53

List the positive and negative regulators

Answer 53

Activator: Pi inhibitor: purine ribonucleotides

Question 54

Pyrophosphate and nitrogenous base are bound to:

Answer 54

1' carbon of ribose

Question 55

Rate limiting/committed step of Purine Synthesis

Answer 55

PRPP Amidotransferase Inhibited by: purine nucleotides Activated by: PRPP

Question 56

Rate limiting step for Pyrimidine Synthesis

Answer 56

CPS II Activated by: PRPP Inhibited by: UTP

Question 57

Pyrimidine bases are produced then attached to:

Answer 57

PRPP

Question 58

Function of ribonucleotide reductase

Answer 58

Convert ribonucleotides into deoxyribonucleotides

Question 59

What inhibits ribonucleotide reductase

Answer 59

Hydroxyurea Anti-tumor drug Used to treat sickle cell anemia Promotes HbF synthesis