Multiple Choice Questions on Purine & Pyrimidine Metabolism
Purine metabolism is a crucial biochemical process that involves the biosynthesis, degradation, and recycling of purine nucleotides, which are essential building blocks of DNA and RNA. The de novo biosynthesis of purines requires several enzymes, including glutamine: phosphoribosyl pyrophosphate (PRPP) amidotransferase, which is a committed step and a target for regulation. Other important enzymes involved in purine biosynthesis include adenylosuccinate synthetase and adenylosuccinate lyase. The degradation of purine nucleotides generates uric acid, which is excreted by the kidneys. Dysregulation of purine metabolism can lead to several diseases, including gout and Lesch-Nyhan syndrome. Understanding the complex regulation of purine metabolism is crucial for the development of novel therapeutic strategies.a) Second Messenger
b) Energy currency and high energy equivalents
c) Regulators of intermediary metabolism
d) All of the above
2. Purines and Pyrimidines are the nitrogen bases present on the nucleotides.
Which of the following is a purine base?
a) Adenosine
b) Cytosine
c) Thymine
d) Uracil
3. Nucleotides are:
a) Purine bases
b) Nitrogen bases+ Pentose Sugar
c) Nitrogen bases + Pentose sugar + Phosphate
d) None of the above
4. Which of the following is not the precursor for the de novo purine biosynthesis?
a) Aspartic Acid
b) Glycine
c) Glutamine
d) Arginine
5. Which of the following serves as the cofactor for the de novo synthesis of purine metabolism?
a) Thiamine
b) Biotin
c) Folate
d) Flavin
6. What is an activator of the enzyme “Glutamine: Phosphoribosyl pyrophosphate amido transferase” a committed step of de novo biosynthesis of purines?
a) Adenosine Monophosphate
b) Guanosine Monophosphate
c) Inosine Monophosphate
d) Phosphoribosyl Pyrophosphate
7. Which of the following is the correct statement regarding Sulfonamides?
a) Structural analogs of PABA that competitively inhibit bacterial synthesis of folic acid
b) Structural analogs of PABA that competitively inhibit the human synthesis of folic acid
c) Structural analogs of PABA that competitively inhibit the bacterial and human synthesis of folic acid
d) None of the above
8. Trimethoprim is a potent antibacterial compound that selectively inhibits bacterial.........................
a) Formyl transferase
b) PRPP synthetase
c) Dihydrofolate reductase
d) None of the above
9. Which of the following is the coenzyme for the synthesis of deoxyribonucleotides catalyzed by an enzyme ribonucleotide reductase?
a) Glutathione
b) Thioredoxin
c) NADPH
d) FADH
10. Severe combined immunodeficiency disease is caused by the deficiency in which of the following enzyme?
a) AMP deaminase
b) Adenosine deaminase
c) PRPP synthetase
d) None of the above
Sulfonamides do not inhibit human synthesis of folic acid because humans do not synthesize folic acid de novo; instead, they obtain it from dietary sources. However, sulfonamides can still affect human cells because they can inhibit the growth of some of the normal microbiota that produce folate, which can lead to deficiencies in folic acid.
8-c)Dihydrofolate reductase
Thioredoxin is a small protein that also plays an important role in reducing the disulfide bond in ribonucleotide reductase. Thioredoxin can transfer electrons to the enzyme, reducing the disulfide bond and providing the necessary reducing power for the conversion of ribonucleotides to deoxyribonucleotides.
10-b)Adenosine deaminase
1) Carbamoyl phosphate synthetase II (CPS-II) is the committed step in the formation of carbamoyl phosphate is:
a) Activated by PRPP
b) Inhibited by UMP
c) Activated by ATP
d) All of the above
2) Which of the following cofactor is used during the conversion of uracil to thymine?
a) S-Adenosyl Methionine
b) Tetrahydrofolate
c) Tetrahydrobiopterin
d) Biotin
3) Which of the following cofactor/coenzyme is NOT utilized in the conversion of ribose to deoxyribose?
a) NADPH
b) FADH2
c) UMP
d) Thioredoxin
4) Followings are the example of nucleosides, EXCEPT:
a) Adenosine
b) Cytidine
c) Cytosine
d) Uridine
5) The Nitrogen of a purine molecule are derived from all of the following amino acids, except?
a) Aspartic Acid and Glutamine
b) Asparagine and Glutamine
c) Glutamate and Alanine
d) Glycine and Alanine
6) Which of the following steps of pyrimidine biosynthesis occurs in mitochondria?
a) Synthesis of carbamoyl phosphate catalyzed by CPS II
b) Conversion of carbamoyl phosphate to carbamoyl aspartate catalyzed by aspartate trans carbamoylase
c) Synthesis of dihydroorotate catalyzed by dihydroorotase
d) Formation of orotic acid catalyzed by dihydroorotase dehydrogenase
7) Methotrexate inhibits which of the following enzyme?
a) ribonucleotide reductase
b) thymidylate synthase
c) dihydrofolate reductase
d) PRPP‑amido transferase
PRPP (phosphoribosyl pyrophosphate) is a molecule that is involved in the biosynthesis of purine nucleotides, which are the other type of nucleotides. PRPP activates CPS-II by promoting the formation of an active enzyme complex. This allows CPS-II to efficiently synthesize carbamoyl phosphate and support pyrimidine nucleotide biosynthesis.
ATP is another molecule that plays a crucial role in activating CPS-II. It provides the energy required for the reaction and also acts as a substrate for the enzyme. Without ATP, CPS-II would not be able to synthesize carbamoyl phosphate and support pyrimidine nucleotide biosynthesis.
Finally, UMP (uridine monophosphate) is a pyrimidine nucleotide that inhibits CPS-II. This is an important regulatory mechanism that prevents overproduction of carbamoyl phosphate, which can lead to imbalances in pyrimidine and purine nucleotide metabolism.
b) Cytosine
c) Thymine
d) Uracil
3. Nucleotides are:
a) Purine bases
b) Nitrogen bases+ Pentose Sugar
c) Nitrogen bases + Pentose sugar + Phosphate
d) None of the above
4. Which of the following is not the precursor for the de novo purine biosynthesis?
a) Aspartic Acid
b) Glycine
c) Glutamine
d) Arginine
5. Which of the following serves as the cofactor for the de novo synthesis of purine metabolism?
a) Thiamine
b) Biotin
c) Folate
d) Flavin
6. What is an activator of the enzyme “Glutamine: Phosphoribosyl pyrophosphate amido transferase” a committed step of de novo biosynthesis of purines?
a) Adenosine Monophosphate
b) Guanosine Monophosphate
c) Inosine Monophosphate
d) Phosphoribosyl Pyrophosphate
7. Which of the following is the correct statement regarding Sulfonamides?
a) Structural analogs of PABA that competitively inhibit bacterial synthesis of folic acid
b) Structural analogs of PABA that competitively inhibit the human synthesis of folic acid
c) Structural analogs of PABA that competitively inhibit the bacterial and human synthesis of folic acid
d) None of the above
8. Trimethoprim is a potent antibacterial compound that selectively inhibits bacterial.........................
a) Formyl transferase
b) PRPP synthetase
c) Dihydrofolate reductase
d) None of the above
9. Which of the following is the coenzyme for the synthesis of deoxyribonucleotides catalyzed by an enzyme ribonucleotide reductase?
a) Glutathione
b) Thioredoxin
c) NADPH
d) FADH
10. Severe combined immunodeficiency disease is caused by the deficiency in which of the following enzyme?
a) AMP deaminase
b) Adenosine deaminase
c) PRPP synthetase
d) None of the above
Answers on Purine metabolism:
1-d)All of the above
1-d)All of the above
Nucleotides have multiple functions in the body, including serving as the building blocks of nucleic acids (DNA and RNA), which are essential for genetic information storage and transfer. However, nucleotides also have other important roles, such as:
a) Second messenger: Certain nucleotides, such as cyclic AMP (cAMP) and cyclic GMP (cGMP), can act as second messengers in cell signaling pathways, transmitting signals from outside the cell to the inside, and regulating various cellular processes.
b) Energy currency and high-energy equivalents: Nucleotides are also involved in energy metabolism, as they serve as precursors for the synthesis of ATP, the main energy currency of the cell. In addition, other nucleotides such as NAD+ and FAD can act as electron carriers in cellular respiration, playing a role in the production of ATP.
c) Regulators of intermediary metabolism: Certain nucleotides can act as allosteric regulators of enzymes involved in intermediary metabolism, such as the TCA cycle and glycolysis. For example, ATP can act as an inhibitor of phosphofructokinase, a key enzyme in glycolysis, thereby regulating glucose metabolism.
a) Second messenger: Certain nucleotides, such as cyclic AMP (cAMP) and cyclic GMP (cGMP), can act as second messengers in cell signaling pathways, transmitting signals from outside the cell to the inside, and regulating various cellular processes.
b) Energy currency and high-energy equivalents: Nucleotides are also involved in energy metabolism, as they serve as precursors for the synthesis of ATP, the main energy currency of the cell. In addition, other nucleotides such as NAD+ and FAD can act as electron carriers in cellular respiration, playing a role in the production of ATP.
c) Regulators of intermediary metabolism: Certain nucleotides can act as allosteric regulators of enzymes involved in intermediary metabolism, such as the TCA cycle and glycolysis. For example, ATP can act as an inhibitor of phosphofructokinase, a key enzyme in glycolysis, thereby regulating glucose metabolism.
2-a)Adenosine
Adenosine is a purine base, along with guanine. Purines have a two-ring structure, consisting of a six-membered ring fused to a five-membered ring. The purine base adenine is found in both DNA and RNA, where it pairs with thymine (in DNA) or uracil (in RNA) via hydrogen bonds.
In contrast, pyrimidines have a single-ring structure. Cytosine and thymine are pyrimidine bases found in DNA, while uracil is a pyrimidine base found in RNA. Pyrimidines pair with complementary bases via hydrogen bonds, with cytosine always pairing with guanine, and thymine (or uracil) always pairing with adenine.
In contrast, pyrimidines have a single-ring structure. Cytosine and thymine are pyrimidine bases found in DNA, while uracil is a pyrimidine base found in RNA. Pyrimidines pair with complementary bases via hydrogen bonds, with cytosine always pairing with guanine, and thymine (or uracil) always pairing with adenine.
3-c)Nitrogen bases + Pentose sugar + Phosphate
Nucleotides are the building blocks of nucleic acids (DNA and RNA) and consist of three components: a nitrogenous base (which can be either a purine or a pyrimidine), a pentose sugar (either ribose in RNA or deoxyribose in DNA), and a phosphate group. The nitrogenous base and the pentose sugar are joined together to form a nucleoside, while the addition of the phosphate group to the nucleoside forms a nucleotide.
4-d)Arginine
De novo purine biosynthesis is the pathway by which purine nucleotides are synthesized from simple precursor molecules. The pathway involves multiple enzymatic reactions and uses several precursor molecules, including:
a) Phosphoribosyl pyrophosphate (PRPP), which is synthesized from ribose 5-phosphate and ATP.
b) Glycine, which is converted into 5,10-methylene-THF (tetrahydrofolate) and then into formyl-THF.
c) Glutamine, which is converted into glutamate and then into 5-phosphoribosyl-1-amine.
d) Aspartic acid, which is converted into 5-phosphoribosyl-1-aspartate (PRPP + aspartic acid), an important intermediate in the pathway.
Arginine, however, is not a precursor molecule for de novo purine biosynthesis. Instead, it is an intermediate in the biosynthesis of the amino acids proline and glutamate.
De novo purine biosynthesis is the pathway by which purine nucleotides are synthesized from simple precursor molecules. The pathway involves multiple enzymatic reactions and uses several precursor molecules, including:
a) Phosphoribosyl pyrophosphate (PRPP), which is synthesized from ribose 5-phosphate and ATP.
b) Glycine, which is converted into 5,10-methylene-THF (tetrahydrofolate) and then into formyl-THF.
c) Glutamine, which is converted into glutamate and then into 5-phosphoribosyl-1-amine.
d) Aspartic acid, which is converted into 5-phosphoribosyl-1-aspartate (PRPP + aspartic acid), an important intermediate in the pathway.
Arginine, however, is not a precursor molecule for de novo purine biosynthesis. Instead, it is an intermediate in the biosynthesis of the amino acids proline and glutamate.
5-c)Folate
Folate (also known as vitamin B9) serves as a cofactor for the de novo synthesis of purine metabolism. Folate is involved in the transfer of one-carbon units, which are essential for the synthesis of the purine ring. Specifically, folate is required for the conversion of dUMP to dTMP, which is a precursor for the synthesis of the DNA nucleotide thymine.
Thiamine (vitamin B1) is a cofactor for several enzymatic reactions involved in carbohydrate metabolism, but it is not directly involved in purine biosynthesis.
Biotin (vitamin B7) is a cofactor for carboxylation reactions, including those involved in fatty acid synthesis, but it is not directly involved in purine biosynthesis.
Flavin (vitamin B2) is a cofactor for the redox reactions involving flavoproteins, but it is not directly involved in purine biosynthesis.
Thiamine (vitamin B1) is a cofactor for several enzymatic reactions involved in carbohydrate metabolism, but it is not directly involved in purine biosynthesis.
Biotin (vitamin B7) is a cofactor for carboxylation reactions, including those involved in fatty acid synthesis, but it is not directly involved in purine biosynthesis.
Flavin (vitamin B2) is a cofactor for the redox reactions involving flavoproteins, but it is not directly involved in purine biosynthesis.
6-d)Phosphoribosyl Pyrophosphate
The enzyme glutamine: phosphoribosyl pyrophosphate amido transferase (GPAT) is a committed step in the de novo biosynthesis of purines. This enzyme catalyzes the transfer of an amido group from glutamine to phosphoribosyl pyrophosphate (PRPP), forming 5-phosphoribosyl-1-amine (PRA) and releasing pyrophosphate. PRA is an intermediate in the biosynthesis of both purine and pyrimidine nucleotides.
The activity of GPAT is regulated by feedback inhibition and activation. The enzyme is activated by its substrate PRPP, which is also a precursor for the biosynthesis of both purine and pyrimidine nucleotides. The binding of PRPP to GPAT increases the enzyme's affinity for its other substrate, glutamine, and stimulates the enzymatic activity.
Adenosine monophosphate (AMP), guanosine monophosphate (GMP), and inosine monophosphate (IMP) are products of the de novo biosynthesis of purines and are involved in feedback inhibition of various enzymes in the pathway, but they do not activate GPAT.
The enzyme glutamine: phosphoribosyl pyrophosphate amido transferase (GPAT) is a committed step in the de novo biosynthesis of purines. This enzyme catalyzes the transfer of an amido group from glutamine to phosphoribosyl pyrophosphate (PRPP), forming 5-phosphoribosyl-1-amine (PRA) and releasing pyrophosphate. PRA is an intermediate in the biosynthesis of both purine and pyrimidine nucleotides.
The activity of GPAT is regulated by feedback inhibition and activation. The enzyme is activated by its substrate PRPP, which is also a precursor for the biosynthesis of both purine and pyrimidine nucleotides. The binding of PRPP to GPAT increases the enzyme's affinity for its other substrate, glutamine, and stimulates the enzymatic activity.
Adenosine monophosphate (AMP), guanosine monophosphate (GMP), and inosine monophosphate (IMP) are products of the de novo biosynthesis of purines and are involved in feedback inhibition of various enzymes in the pathway, but they do not activate GPAT.
7-a)Structural analogs of PABA that competitively inhibit bacterial synthesis of folic acid
Sulfonamides are a class of antibiotics that are structural analogs of para-aminobenzoic acid (PABA), a precursor molecule for the biosynthesis of folic acid. Folic acid is an essential vitamin that is required for the synthesis of DNA, RNA, and other important biomolecules. In bacteria, folic acid synthesis occurs via the de novo pathway, which is different from the pathway in humans. Sulfonamides competitively inhibit bacterial synthesis of folic acid by binding to the enzyme dihydropteroate synthase (DHPS), which is involved in the synthesis of dihydrofolic acid, an intermediate in the pathway.Sulfonamides do not inhibit human synthesis of folic acid because humans do not synthesize folic acid de novo; instead, they obtain it from dietary sources. However, sulfonamides can still affect human cells because they can inhibit the growth of some of the normal microbiota that produce folate, which can lead to deficiencies in folic acid.
8-c)Dihydrofolate reductase
Trimethoprim is a synthetic antibacterial drug that selectively inhibits bacterial dihydrofolate reductase (DHFR), an enzyme that catalyzes the conversion of dihydrofolic acid to tetrahydrofolic acid, the active form of folate. Folate is an essential vitamin that is required for the synthesis of DNA, RNA, and other important biomolecules. Inhibition of DHFR leads to a depletion of tetrahydrofolic acid, which disrupts bacterial nucleic acid synthesis and cell growth.
Trimethoprim is often used in combination with sulfonamides, which also inhibit bacterial folate synthesis, to achieve a synergistic effect on bacterial growth inhibition.
Trimethoprim is often used in combination with sulfonamides, which also inhibit bacterial folate synthesis, to achieve a synergistic effect on bacterial growth inhibition.
9-b)Thioredoxin
Ribonucleotide reductase is an enzyme that converts ribonucleotides to deoxyribonucleotides, the building blocks of DNA. Thioredoxin is a small protein that also plays an important role in reducing the disulfide bond in ribonucleotide reductase. Thioredoxin can transfer electrons to the enzyme, reducing the disulfide bond and providing the necessary reducing power for the conversion of ribonucleotides to deoxyribonucleotides.
10-b)Adenosine deaminase
Severe combined immunodeficiency disease (SCID) is caused by the deficiency of adenosine deaminase (ADA), which is an enzyme involved in purine metabolism. ADA plays a critical role in the breakdown of adenosine and deoxyadenosine to inosine and deoxyinosine, respectively, which are then further metabolized to uric acid. In the absence of ADA activity, toxic levels of adenosine and deoxyadenosine accumulate in the body, leading to severe combined immunodeficiency disease.
Pyrimidine metabolism is a vital cellular process that involves the biosynthesis and degradation of pyrimidine nucleotides, which are essential building blocks for DNA, RNA, and other important biomolecules. Pyrimidine metabolism is tightly regulated to maintain the proper balance of nucleotides for cellular functions. The de novo biosynthesis of pyrimidine nucleotides starts with the conversion of glutamine and aspartate into carbamoyl phosphate, which then combines with aspartate to form dihydroorotate. This is then converted to orotate, which is further converted into uridine monophosphate (UMP). The degradation of pyrimidine nucleotides involves the breakdown of UMP into uracil, which is then converted to β-alanine and then to malonyl-CoA. This process provides the cell with important sources of carbon and nitrogen for other metabolic processes. Dysfunction in pyrimidine metabolism can lead to a variety of disorders, including cancer and neurological disorders.
Questions on Pyrimidine Metabolism
1) Carbamoyl phosphate synthetase II (CPS-II) is the committed step in the formation of carbamoyl phosphate is:
a) Activated by PRPP
b) Inhibited by UMP
c) Activated by ATP
d) All of the above
2) Which of the following cofactor is used during the conversion of uracil to thymine?
a) S-Adenosyl Methionine
b) Tetrahydrofolate
c) Tetrahydrobiopterin
d) Biotin
3) Which of the following cofactor/coenzyme is NOT utilized in the conversion of ribose to deoxyribose?
a) NADPH
b) FADH2
c) UMP
d) Thioredoxin
4) Followings are the example of nucleosides, EXCEPT:
a) Adenosine
b) Cytidine
c) Cytosine
d) Uridine
5) The Nitrogen of a purine molecule are derived from all of the following amino acids, except?
a) Aspartic Acid and Glutamine
b) Asparagine and Glutamine
c) Glutamate and Alanine
d) Glycine and Alanine
6) Which of the following steps of pyrimidine biosynthesis occurs in mitochondria?
a) Synthesis of carbamoyl phosphate catalyzed by CPS II
b) Conversion of carbamoyl phosphate to carbamoyl aspartate catalyzed by aspartate trans carbamoylase
c) Synthesis of dihydroorotate catalyzed by dihydroorotase
d) Formation of orotic acid catalyzed by dihydroorotase dehydrogenase
7) Methotrexate inhibits which of the following enzyme?
a) ribonucleotide reductase
b) thymidylate synthase
c) dihydrofolate reductase
d) PRPP‑amido transferase
8) Orotic aciduria is an inherited genetic disorder caused by a deficiency in which of the following enzyme?
a) CPS II
b) Aspartate trans carbamoylase
c) Dihydroorotase dehydrogenase
d) UMP synthase
a) CPS II
b) Aspartate trans carbamoylase
c) Dihydroorotase dehydrogenase
d) UMP synthase
9) Fluorouracil is an anti-tumor agent that binds and irreversibly inhibits which of the following enzyme?
a) ribonucleotide reductase
b) thymidylate synthase
c) dihydrofolate reductase
d) PRPP‑amido transferase
10) Which of the following is the degradation product of pyrimidines?
a) beta-alanine
b) Uric acid
c) Allantoin
d) Glycine
a) ribonucleotide reductase
b) thymidylate synthase
c) dihydrofolate reductase
d) PRPP‑amido transferase
10) Which of the following is the degradation product of pyrimidines?
a) beta-alanine
b) Uric acid
c) Allantoin
d) Glycine
Answers: (Pyrimidine metabolism)
1- d)All of the above
Carbamoyl phosphate synthetase II (CPS-II) is an enzyme involved in the biosynthesis of pyrimidines, which are one of the two types of nucleotides. Pyrimidine nucleotides are essential for DNA and RNA synthesis and play important roles in cell division, growth, and proliferation. CPS-II catalyzes the formation of carbamoyl phosphate, a precursor for the biosynthesis of pyrimidine nucleotides.1- d)All of the above
PRPP (phosphoribosyl pyrophosphate) is a molecule that is involved in the biosynthesis of purine nucleotides, which are the other type of nucleotides. PRPP activates CPS-II by promoting the formation of an active enzyme complex. This allows CPS-II to efficiently synthesize carbamoyl phosphate and support pyrimidine nucleotide biosynthesis.
ATP is another molecule that plays a crucial role in activating CPS-II. It provides the energy required for the reaction and also acts as a substrate for the enzyme. Without ATP, CPS-II would not be able to synthesize carbamoyl phosphate and support pyrimidine nucleotide biosynthesis.
Finally, UMP (uridine monophosphate) is a pyrimidine nucleotide that inhibits CPS-II. This is an important regulatory mechanism that prevents overproduction of carbamoyl phosphate, which can lead to imbalances in pyrimidine and purine nucleotide metabolism.
2- b)Tetrahydrofolate
3- c)UMP
4- c)Cytosine
5- a)Aspartic Acid and Glutamine
6- d)Formation of orotic acid catalyzed by dihydroorotase dehydrogenase
7- b)thymidylate synthase
8- d)UMP synthase
9- b) thymidylate synthase
10-a) beta-alanine
4- c)Cytosine
5- a)Aspartic Acid and Glutamine
6- d)Formation of orotic acid catalyzed by dihydroorotase dehydrogenase
7- b)thymidylate synthase
8- d)UMP synthase
9- b) thymidylate synthase
10-a) beta-alanine
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