Biochemistry Wk 10-LOOK AT PPT

Question 1

BIOMEDICAL IMPORTANCE Nucleotide and nucleotide derivatives have important functions in the body.

Answer 1

• Buildingblocksofnucleicacids
• Sourceofenergy
• Signalmolecules
• Activatorsforthetransferofgroups • Regulators
• Carriermolecules

Question 2

Purine and pyrimidine

Answer 2

Purinesandpyrimidinesarenitrogen-containing heterocycles
• Theyarefundamentalcomponentsof nucleotides in DNA and RNA and are essential for the storage of information in the cell.

Question 3

Nucleosides

Answer 3

Nucleoside: base and sugar (ribose or deoxyribose), linked by an N-glycosidic bond
• If the sugar is ribose, a ribonucleoside is produced, and if the sugar is 2-deoxyribose, a deoxyribonucleoside is produced.
• The ribonucleosides of A, G, C, and U are named adenosine, guanosine, cytidine, and uridine, respectively.
• The deoxyribonucleosides of A, G, C, and T have the added prefix deoxy-

Question 4

Nucleotides

Answer 4

• The addition of one or more phosphate groups to a nucleoside produces a nucleotide.
• If one phosphate group is attached to the 5′- carbon of the pentose, the structure is a nucleoside monophosphate
• If a second or third phosphate is added to the nucleoside, a nucleoside diphosphate/triphosphate

Question 5

PURINE NUCLEOTIDE SYNTHESIS

Answer 5

The atoms of the purine ring are contributed by a number of compounds, including amino acids (aspartate, glycine, and glutamine), carbon dioxide (CO2), and N10-formyltetrahydrofolate (N10-formyl-THF)

Question 6

Biosynthesis of nucleotides

Answer 6

Major site- liver

Two pathways:
The de novo pathways begins with their metabolic precursors (a.a, ribose 5P, CO2,NH3)

Salvage pathway- recycling of the free bases and nucleosides released from nuclei acid breakdown

Question 7

De novo synthesis

Answer 7

Begins with 5- phophoribosyl1 pyrophospahte (PRPP)

Synthesis of PRPP from ATP and ribose 5-phosphate is catalyzed by PRPP synthetase. This X- linked enzyme is activated by inorganic phosphate and inhibited by purine nucleotides

Question 8

5-Phosphoribosylamine synthesis

LOOK AT GOODNOTES

Answer 8

The amide group of glutamine replaces the pyrophosphate group attached to carbon 1 of PRPP. This is the committed step in purine nucleotide biosynthesis. The enzyme that catalyzes the reaction, glutamine:phosphoribosylpyrophosphate amidotransferase (GPAT)

Question 9

Adenosine and guanosine monophosphate synthesis

Answer 9

LOOK AT GOODNOTES

Question 10

Nucleoside di and triphophate synthesis

Answer 10

Nucleoside diphosphates are synthesized from the corresponding nucleoside monophosphates by base-specific nucleoside monophosphate kinases

LOOK AT GOODNOTES

Question 11

Ribonucleotide reductase

Answer 11

• Ribonucleotide reductase is a dimer composed of two nonidentical subunits, R1 and the smaller R2, and is specific for the reduction of purine nucleoside diphosphates and pyrimidine nucleoside diphosphates to their deoxy forms.
• The immediate donors of the hydrogen atoms needed for the reduction of the 2′-hydroxyl group are two sulfhydryl (–SH) groups on the enzyme itself (R1 subunit)

Question 12

Regulation of purine biosynthesis

Answer 12

Biosynthesis of the nucleotide skeleton is an energy-intensive process that must be tightly regulated.
The key enzyme, glutamine-PRPP amidotransferase, is activated by PRPP and inhibited by ADP, ATP, GDP, and GTP.
Not shown here: High levels of ATP promote the formation of GMP, whereas high levels of GTP promote the formation of ATP. Adenylosuccinate synthetase is inhibited by AMP, and IMP dehydrogenase is inhibited by GMP (negative feedback inhibition)

Question 13

De NOVO PURINE SYNTHESIS

Answer 13

Purine: 6 mercaptopurine and its prodrug azathioprine: inhibit de novo purine synthesis

Mycophenolate and ribavirin: inhibit Inosine monophosphate

Purine and pyrimidine:
Hydroxyurea: inhibits ribonucleotide reductase
Methotrexate, trimethoprim and pyrimethamine: inhibit dihydrofolate reductase (decreases deoxythymidine monophosphate)

Question 14

Inhibitors

Answer 14

They are extremely toxic to tissues especially to developing structures such as the foetus, or cell types that normally replicate rapidly such as those of the bone marrow, skin, GI tract, immune system or hair follicles.

Individuals taking such anti cancer drugs can have adverse effects including anaemia, scaly skin, GI tract disturbance,immunodeficiency and hair loss

Question 15

Quiescent cells

Answer 15

Can enter the G1 phase from the G0 phase when stimulated

Examples:
- cells in exo/endocrine glands
Hepatocytes
Lymphocytes
Periosteal cells
Cells of the PCT

Question 16

Purine salvage pathway

Answer 16

Purines that result from the normal turnover of cellular nucleic acids, or the small amount that is obtained from the diet and not degraded, can be converted to nucleoside triphosphates and used by the body.
This is referred to as the salvage pathway for purines

Question 17

Purine salvage deficiencies

Answer 17

Look at GOODNOTES

Question 18

Case- A 1-year-old boy was brought to the pediatrician due to a developmental delay, biting of his lips and fingers, and the presence of orange crystals in his diapers. Enzymatic analysis shows loss of 99% of the activity of a particular enzyme. The defective enzyme in this disorder would normally utilize which of the following as a substrate?

Answer 18

Lesch- Nyhan syndrome

Hyperuricemia
Gout
Pissed off ( aggression, self mutilation)
Retardation
DysTonia

Question 19

LOOK AT GOODNOTES FOR SYMPTOMS, TREATMENT

Question 20

Prognosis:

Answer 20

● The prognosis for LNS is poor
● Because there are no treatments for the neurological effects of the syndrome as self- mutilation and may result in severe retardation and death.
● The build-up of excessive uric acid in the body causes painful episodes of joints.