Lecture 20 Nucleotide Structure, Function, and Metabolism

Question 1

DNA binding proteins involved in forming chromosomes are:

Answer 1

Histones and non-histone chromosomal proteins

Question 2

Protein + nuclear DNA = ?

Answer 2

Chromatin

Question 3

Nucleic Acids

Answer 3

Polynucleotides (DNA and RNA)

Question 4

Nucleotides

Answer 4

Base, sugar, and phosphate

Question 5

Nucleosides

Answer 5

Base and Sugar

Question 6

Nucleotides are the phosphate esters of:

Answer 6

Nucleosides

Question 7

Purines

Answer 7

2 rings

Adenine and Guanine

Question 8

Pyrimidines

Answer 8

1 ring

Thymine, Cytosine, and Uracil

Question 9

Nomenclature of Purines and Pyrimidines

Base - Nucleoside - Nucleotide

Answer 9

Adenine (Ade) - Adenosine (A) - AMP
Guanine (Gua) - Guanosine (G) - GMP
Cytosine (Cyt) - Cytidine (C) - CMP
Uracil (Ura) - Uridine (U) - UMP
Thymine (Thy) - Thymidine (T) - TMP

Question 10

In DNA, there are ___ base pairs per turn.

Answer 10

10

Question 11

DNA exist in two forms. What are they and which one is more prominent?

Answer 11

A and B

Most B form (hydrated)

Question 12

Ribonucleases (RNA)

Deoxyribonucleases (DNA)

Answer 12

Convert RNA and DNA to short oligomers

Question 13

Phosphodiesterase

Answer 13

Convert oligomers to nucleotide monophosphates (NMPs) or deoxynucleoside monophosphates (dNMPs)

Question 14

Nucleotidase

Answer 14

Convert NMPs and dNMPs into nucleosides and deoxynucleosides

Question 15

Nucleosidase

Answer 15

Remove ribose group and covert them into pyrimidines and purines

Question 16

Adenosine Deaminase (ADA)

Answer 16

Plays an important role in adenosine homeostasis and modulates signaling by extracellular adenosine and also contributes indirectly to signaling

Question 17

Overproduction of ADA

Answer 17

Causes hemolytic anemia (rare). Increased degradation of adenosine depletes adenine nucleotide pool and triggers premature destruction of RBCs

Question 18

Underproduction of ADA

Answer 18

Associated with the second most common form of severe combined immunodeficiency

Question 19

Xanthine Oxidase

Answer 19

Catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid

Question 20

Describe the Xanthine Oxidase Molecule

Answer 20

2 flavin adenine dinucleotides (FADs), 2 Mo atoms, and 8 Fe atoms per molecule of enzyme

Question 21

Xanthine Oxidase is a drug target for the treatment of:

Answer 21

Gout

Question 22

Severe Combined Immunodeficiency (SCID)

Answer 22

Defective B and T cells
Most common form is x-linked, hence patients are male
“Bubble Boy”

Question 23

ADA deficiency

Answer 23

Most pronounced in lymphocytes
Results in high amounts of adenosine which is then converted into dATP, high levels of which block synthesis of all other dNDPs and dNTPs

Question 24

Gout

Answer 24

Characterized by intensely painful and inflamed joints
High levels of uric acid levels in blood resulting from over production of uric acid or under-excretion of uric acid (secondary hyperuricemia)

Question 25

Hyperuricemia

Answer 25

Uric acid concentration exceeds pasma solubility

Question 26

Treatment for gout

Answer 26

Colchicine (decreases movement of granulocytes to the affected area) and allopurinol that inhibits xanthine oxidase to form the more soluble hypoxanthine

Question 27

Dietary pyrimidines are converted readily to:

Answer 27

metabolized ketogenic or glucogenic, water soluble compounds such as malonyl CoA, methyl malonyl CoA, and succinyl CoA

Question 28

The source of ring atoms is purine synthesis:

Answer 28

CO2, Gln, Gly, Asp, N10-formyl THF

Question 29

The source of ring atoms in pyrimidine synthesis:

Answer 29

HCO3, Gln, Asp, N5, N10-methylene THF

Question 30

The committed step in purine synthesis is the formation of the:

Answer 30

Phosphoribosyl amine

Question 31

What is the intermediate formed in all purine synthesis?

Answer 31

Inosine Monophosphate (IMP)

Question 32

Name the two salvage enzymes of Purine Biosynthesis

Answer 32

Hypoxanthine guanine phosphoribosyl transferase | Adenine phosphoribosyl transferase

Question 33

PRPP (Phosphoribosyl pyrophosphate)

Answer 33

Central constituent of nucleotide metabolism | Synthesized from ribose phosphate and ATP

Question 34

In purine synthesis, the ribose is initially contributed by:

Answer 34

Phosphoribosylpyrophosphate

Question 35

True or False: | In purine synthesis, the purine ring is synthesized before being attached to the ribose.

Answer 35

False. | The purine ring is synthesized attached to ribose phosphate

Question 36

Methotrexate

Answer 36

Antineoplastic agent Inhibitor of DNA synthesis Binds dihydrofolate reductase 100 fold more tightly; great competitive inhibitor

Question 37

What parts of purine synthesis are feedback inhibited?

Answer 37

Synthesis of PRPP and PR-amine | Synthesis of AMP and GMP from IMP

Question 38

AMP synthesis is stimulated by:

Answer 38

GTP

Question 39

GMP synthesis is stimulated by:

Answer 39

ATP

Question 40

The nucleoside phosphates can be interconverted by exchange of phosphates with each other catalyzed by:

Answer 40

Nucleoside monophosphate kinases and diphosphate kinases

Question 41

True or False: | In pyrimidine synthesis, the pyrimidine base is built before it is attached to the ribose sugar.

Answer 41

True