L14: Cell Metabolism-nucleotide Metabolism

Question 1

Nucleotide structure

Answer 1

1. Ribose / Deoxyribose (Pentose)
2. Phosphate
3. Base (purine / pyrimidine)

Purine: Adenine, Guanine
Pyrimidine: Cytosine, Uracil, Thymine

Question 2

Nucleotide vs Nucleoside

Answer 2

Nucleoside: Sugar + Base (linked by glycosidic linkage)
Nucleotide: Sugar + Base + Phosphate

Question 3

Combinations of nucleotide

Answer 3

Nucleotide
—> Ribonucleotide —> Purine/Pyrimidine base —> High/Low energy form (mono, di, triphosphate)
—> Deoxyribonucleotide —> Purine/Pyrimidine base —> High/Low energy form (mono, di, triphosphate)
Total: 2 x (2+3) x 3 = 30 combinations

Question 4

Examples of nucleotide

Answer 4

• ATP, ADP, AMP
• FAD (riboflavin adenine dinucleotide), NAD (nicotinamide adenine dinucleotide)
• Coenzyme A
• DNA (multiple nucleotide joined together)

Question 5

***Functions of nucleotide

Answer 5

1. Energy provider (ATP)
2. Co-enzymes (NAD, FAD)
3. Hormone-like molecule (Adenosine: nucleoside)
4. Molecular times in intracellular signalling (GDP/GTP in GPCR)
5. Synthesis of RNA (information transfer: Ribonucleoside triphosphate —RNA polymerase—> RNA)
6. Synthesis of DNA (hereditary information preservation: Deoxyribonucleoside triphosphate —DNA polymerase—> DNA)

Question 6

How to synthesize NDP/NTP, dNDP/dNTP from NMP

Answer 6

增加P: Use ATP to provide phosphate to NMP (low energy)
NMP —> NDP/NTP —> dNDP/dNTP (high energy, used to build RNA/DNA)

去氧: NDP —(NADPH—>NADH)—> dNDP (NADPH reduces NDP using Ribonucleotide reductase)

Question 7

De novo synthesis of nucleotide bases

Answer 7

Purine base:

1. Aspartate
2. Glycine
3. Formate
4. Amide N of glutamine

Pyrimidine base:

1. Aspartate
2. Carbamoyl phosphate

Question 8

Uric acid hazard

Answer 8

Purine nucleotide
—(remove phosphate)—> Purine nucleoside
—(remove ribose)—> Xanthine
—(Xanthine oxidase)—> Uric acid (normally can be excreted in urine)

Allopurinol / Febuxostat: Xanthine oxidase inhibitor

Question 9

Salvaging pathway and defects

Answer 9

Purine nucleotide
—> Purine nucleoside
—> Hypoxanthine/Guanine —> back to nucleotide intermediate —> recycled (Salvaging pathway)

Defects in enzyme in salvaging pathway
—> not enough purine bases recycled + channeled to form uric acid instead
—> impaired brain development
—> Lesch Nyhan syndrome

Question 10

Synthesis of dTMP for DNA synthesis

Answer 10

UDP —> dUDP —> dUTP —> dUMP —> dTMP —> DNA synthesis
(Since uracil cannot be used for DNA, must be substituted by thymine)

dUMP —(Tetrahydrofolate—>dihydrofolate)—> dTMP

***Methotrexate, Fluorouracil, Trimethroprim inhibit Dihydrofolate Reductase:
Dihydrofolate —X—> Tetrahydrofolate —> cannot synthesize dTMP —> stop cancer