18 Purine & Pyrimidine metabolism

Question 1

What is Nucleoside

Answer 1

Base+Sugar

Question 2

What is Nucleotide

Answer 2

Base+Sugar+P

Question 3

Name purines and their specifities

Answer 3

Adenine: NH2 on top of first ring
Guanine: ketone O on top and NH2 on down of first ring
Hypoxanthine: like guanine without amine group

Question 4

Name Pyrimidines and their specifities

Answer 4

Cytosine: amine group on top, ketone on down
Uracil: Ketone on top and down
Thymine: like uracil but with an extra methyl group

Question 5

Nucleotides function

Answer 5

DNA and RNA synthesis (DNA replication and transcription)

Energy transfer

Question 6

What is the Primary Substance to produce nucleotides, what is its origin and how does it produce

Answer 6

Ribose 5-phosphate for nucleotide synthesis is derived from the hexose monophosphate shunt
It is activated by the addition of pyrophosphate from ATP, forming phosphoribosyl pyrophosphate (PRPP) using PRPP synthetase

Question 7

In which ways are Nucleotides synthesized

Answer 7

de novo synthesis, which occurs predominantly in the liver: from smaller precursors and PRPP is added to the pathway at some point
Salvage pathways: Synthesis in the liver and transport to other tissues
Digestion of endogenous nucleic acids (cell death, RNA turnover)
Capacity for de novo synthesis is insufficient in many cells, and the salvage pathway is essential

Question 8

Explain 1st step of De novo Pyrimidine synthesis

Answer 8

From CO2, glutamine and ATP in the cytoplasm by cytoplasmic carbamoyl phosphate synthetase-2 to carbamoyl phosphate
then aspartate is added and end product will be Orotic acid (a pyrimidine precursor)

Question 9

Explain 2nd step of De novo Pyrimidine synthesis

Answer 9

Orotic Acids by UMP synthase with usage of PRPP and release of a CO2 produce UMP(Uridine monophosphate)

Question 10

how do deoxy pyrimidines are synthesized for DNA

Answer 10

UDP(must be a diphosphate) by Ribonucleotide reductase will produce dUDP

Question 11

How does Thymidine synthesize

Answer 11

Thymidylate synthase with the help of THF Methylates dUMP to dTMP

Question 12

what are the different types of Orotic aciduria

Answer 12

Hyperammonemia, No megaloblastic anemia
Urea Cycle: Enzyme deficient is OTC

Megaloblastic anemia, No hyperammonemia
Pyrimidine Synthesis: Enzyme deficient is UMP synthase

Question 13

What is the symptoms and pattern of inheritance in UMP synthase defficiency
what is the treatment

Answer 13

Autosomal recessive disorder
Megaloblastic anemia in infants
Orotic aciduria: Orotic acid crystals and orotic acid urinary obstruction
Uridine administration relieves the symptoms by bypassing the defect
Uridine is salvaged to UMP, which feedback-inhibits carbamoyl phosphate synthase-2, preventing orotic acid formation

Question 14

what is the effect of Hydroxyurea

what is its usage and which stage does it stop

Answer 14

Ribonucleotide reductase inhibitor, S phase

An antineoplastic agent that blocks reduction of NTPs to dNTPs for DNA synthesis

Question 15

what is the effect of 5-Fluorouracil

what is its usage and which stage does it stop

Answer 15

Thymidylate synthase inhibitor, S phase

An antineoplastic agent that blocks methylation of dUMP to dTMP

Question 16

what is the effect of Methotrexate

what is its usage and which stage does it stop

Answer 16

Dihydrofolate reductase inhibitor, S phase

An antineoplastic agent that blocks convertion of DHF to THF: Without DHFR, thymidylate synthesis will eventually stop

Question 17

what is the effect and usage of Cotrimoxazole

Answer 17

Sulfamethoxazole: inhibit conversion of PABA to folic acid in prokaryotic cells
Trimethoprim: Inhibit conversion of DHF to THF in prokaryotic cells
a synergistic antibiotic

Question 18

what is the effect of Pyrimethamine

Answer 18

Inhibit conversion of DHF to THF in protozoal cells

Question 19

What are the features of Ribonucleotide reductase

Answer 19

Required for formation of the deoxyribonucleotides for DNA synthesis
All four nucleotide substrates must be diphosphates

dADP and dATP strongly inhibit ribonucleotide reductase.

Hydroxyurea, an anticancer drug, blocks DNA synthesis indirectly by inhibiting ribonucleotide reductase

Question 20

How are Pyrimidines catabolized

Answer 20

Pyrimidines may be completely catabolized and NH4+ is produced
or recycled by pyrimidine salvage enzymes

Question 21

What is the main difference between Purines and Pyrimidines synthesis

Answer 21

in Pyrimidines: first the precursor is built and then the sugar will be added
in Purines first the sugar is produced and by adding some nitrogen group the nucleotide is produced

Question 22

Explain 1st step of De novo Purine synthesis

Answer 22

Ribose 5-phosphate by PRPP synthase produce PRPP
then by PRPP amidotransferase, 5-phosphoribosylamine will be produced
PRPP amidotransferase is the most important enzyme which catalyzes rate-limiting reaction of the pathway

Question 23

Explain 2nd step of De novo Purine synthesis

Answer 23

5 phosphoribosylamine with the help of Glycine, Aspartate, Glutamine and THF as a carbon donor produce Inosine monophosphate(hypoxanthine as the base)
the by joining of Glutamine amine group GMP is produced
or by joining of Aspartate amine group AMP is produced

Question 24

what control PRPP amidotransferase as the rate limiting enzyme of purine synthesis

Answer 24

It is inhibited by the three purine nucleotide end products AMP, GMP, and IMP

Question 25

what is the effect and usage of allopurinol

Answer 25

Inhibit PRPP amidotransferase, used for gout

It’s a purine analogue and must be converted to their respective nucleotides by HPRT within cells

Question 26

what is the effect and usage of 6-mercaptopurine

Answer 26

Inhibit PRPP amidotransferase, used as an antineoplastic

It’s a purine analogue and must be converted to their respective nucleotides by HPRT within cells

Question 27

what is the effect and usage of Azathioprine

Answer 27

Azathioprine produce 6-mercaptopurine

Inhibit PRPP amidotransferase, used as an antineoplastic

Question 28

Which organisms lack the necessary genes in the purine pathway
what is their solution for their problem

Answer 28

Protozoan and multicellular parasites and many obligate parasites, such as Chlamydia cannot synthesize purines de novo
They have elaborate salvage mechanisms for acquiring purines from the host