Nucleotide Synthesis And Metabolism Flashcards
What are the components of a nucleotide
Phosphate group
Nitrogenous Base
Ribose or pentose
What are the components of a nucleoside
Nitrogenous Base
Ribose / Pentose sugar
What are the different Purines
Adenine, Guanine
What are the different Pyrimidines
Uracil, Thymine, Cytosine
CUT
Which nitrogen base has 2 ring structures
Adenine
Guanine
(Purine)
Which nitrogenous base has 1 ring structure
Cytosine
Thymine
Uracil
True or false, thymine is found in RNA
False, it is found in DNA
Uracil is found in RNA
What suffix is added to nucleoside s when they become nucleotide
-ylate
What is Chargraffs rule
A%= T% G%= C%
I.e purines = pyrimidines
In complementary base pairing, which pair has
I) double bonds
II) triple bonds
A-T
G-C
True or False, DNA structures are parallel
False, they are anti parallel
What are the two Anti- tumor drugs involved in disrupting the DNA structure, used mainly for patients with Leukemia
Daunorubicin
Doxorubicin
How does Daunorubicin and Doxorubicin disrupts the DNA structure
Intercalates between the bases of DNA, preventing proper replication of DNA
What drug is used in treating bladder and lung tumors
Cisplatin
How does Cisplatin disrupt DNA replication
Distorts and Malfunction of DNA
What are histones predominantly made from
Arginine and lysine
What are the components of chromatin
DNA, Histone
What are the two types of pathways for nucleotide Synthesis
De novo
Salvage Pathway
What are the metabolic precursors in de novo Synthesis
Amino Acids
Ribose 5- phosphate
CO2
NH3
What is the pyrimidine ring synthesized as
Orotate
In which pathway do the free bases act as intemediates
Salvage Pathway
What are the shared precursors in the de novo pathway of pyrimidine and purine
PRPP (phospho-robosyl-pyrophosphate)
What are the sources of amino groups
Glutamine
Aspartate
Describe the steps involve in the De novo synthesis of Purines
(Please include enzymes and what inhibits each step)
(Insert picture)
What enzymes are involved in the salvage pathway of purine bases
- Adenine phosphoribosyltransferse
2. Hypoxanthine- Guaninephosphoribosyltransferase (HGPRT)
Which pathway uses less energy
Salvage pathway
True or False, Salvage Pathway of Purine Bases are irreversible
True
Describe the steps involved in the salvage pathway of purines
(Please include enzyme used)
(Insert Picture here)
Describe the steps involved in the degradation of Purines
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What enzyme deficiency is present in SCID
Adenosine Deaminase
What 2 molecules can adenosine be converted to when ADA isn’t present
dATP and ribonucleotide
How does ADA deficiency cause SCID
(Insert picture here)
What two methods can be used to cure SCID
- Bone Marrow Replacement Therapy (human leukocyte antigen HLA)
2, Enzyme Replacment Therapy
Synthetic ADA administered in complex with PEG (polyethylene glycol) ADA-PEG
Hyperurciemia and Gout May accompany which conditions
(Insert Picture Here)
What drug is used to inhibit xanthine oxidase for the treatment of Gout
Allopurinol
What does xanthine oxidase convert allopurinol into
Oxypurinol (alloxanthine)
What two drugs are used in the treatment of acute attacks of gout
Colchicine, Indomethacin
What drug is used for chronic hyperuricemia caused by underexcretion of Uric acid
Probenecid
Lesch- Nyhan Syndrome is due to a near complete deficiency of what enzyme
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
What are the symptoms of Lesch Nyhan Syndrome
Mental Retardation
Compulsive destructive behavior (biting of hands and lips)
Involuntary movements
Heritable cause of hyperuricemia
Death often in first decade (renal failure)
What is used in the treatment of Lesch-Nyhan Syndrome
Allopurinol
In pyrimidine de novo synthesis,
________ acts as an C and N donor
________ acts as a N donor
________ acts as a carbon donor
Aspartate
Glutamine
CO2
What are the symptoms of Hereditary Orotic Aciduria
Severe Anemia
Growth retardation
High Levels of Orotic Acid Excretion
What is the major regulatory step in making Orotate in pyrimidine biosynthesis
Carbomyl Phosphate Synthase II
How does ingesting Uridine treat Hereditary Orotic Aciduria
- Uridine is broken down into UMP by the enzyme uridine phosphorylase in the salvage pathway
- UMP is converted into UDP and UTP
- UTP inhibits the enzyme carbomyl phosphate synthase II through a negative feedback mechanism
- This enzyme is a major regulatory step in the production of orotate thereby decreasing Orotic Acid levels
What is the biochemical basis of Hereditary Orotic Aciduria
Defect in one or both activities of
- Orotate phosphoribosyl transferase
- Oritidine Decarboxylase
- Separate catalytic domain of the enzyme UMP synthase
What is the chemical reaction for the salvage pathway of pyrimidine bases
(Please include enzyme )
(Insert Picture here )
What enzyme is used in the conversion of ribonucleotides to deoxyribonucleotides
Ribonucleotide reductase
Describe the steps involved in the formation of dTMP
It involves the the methylation of D-uridylate
The methyl group is from the compound N- Methylenetetrahydrofolate
With the use of the enzyme thymidylate synthase that catalyses the reaction
Tetrahydrofolate must be federated in order for this reaction to occur
Describe the steps involved in the regeneration of tetrahydrofolate (include enzyme)
Synthesis of dihydrofolate from the formation of dTMP
Dihyrofolate + NADPH(reducing agent) + dihyrdofolate reductase (enzyme)
Describe the steps involved in the degradation of TMP
(Inserts Picture here)
Describe the steps involved in the degradation of CMP
(Insert Picture here)
What compound which is excreted in urine is produced at increased levels during chemo and radiation for cancer patients
B - aminoisobutyric acid
