Biochem - Molecular (Pyrimidine & Purine Synthesis/Deficiencies & Genetic code features) Flashcards
Pg. 67-68 in First Aid 2014 Sections include: -De novo pyrimidine and purine synthesis -Purine salvage deficiencies -Genetic code features
In general, what are the 2 major steps in de novo purine synthesis?
(1) Start with sugar + phosphate (PRPP) (2) Add base
In general, what are the 3 major steps in de novo pyrimidine synthesis?
(1) Make temporary base (orotic acid) (2) Add sugar + phosphate (PRPP) (3) Modify base
Draw out the key reactions/steps in the de novo pyrimidine synthesis pathway, including and labeling where the following inhibitors act: (1) 5-FU (2) Hydroxyurea (3) Leflunomide (4) Impaired in orotic aciduria (5) MTX, TMP, pyrimethamine.
See p. 67 in First Aid 2014 for left half of visual
Draw out the key reactions/steps in the de novo purine synthesis pathway, including and labeling where the following inhibitors act: (1) 6-MP (2) Mycophenolate, ribavirin.
See p. 67 in First Aid 2014 for right half of visual
What amino acid does pyrimidine base production require?
Pyrimidine base production (requires aspartate)
What 4 amino acids or other products does de novo purine base production require?
de novo requires aspartate, glycine, glutamine, and THF
In pyrimidine synthesis, which kind of nucleotides are synthesized first, to what kind are they synthesized, and how?
Ribonucleotides are synthesized first and are converted to deoxyribonucleotides by ribonucleotide reductase
In what 2 metabolic pathways is carbamoyl phosphate involved?
Carbamoyl phosphate is involved in 2 metabolic pathways: de novo pyrimidine synthesis and the urea cycle
Name 6 antineoplastic/antibiotic drugs that function by interfering with nucleotide synthesis at different reactions.
(1) Leflunomide (2) Mycophenolate, Ribavirin (3) Hydroxyurea (4) 6-mercaptopurine (6-MP), Azathioprine (5) 5-fluorouracil (5-FU) (6) Methotrexate (MTX), Trimethoprim (TMP), and Pyrimethamine
What does Leflunomide inhibit?
Leflunomide inhibits dihydroorotate dehydrogenase
What does Mycophenolate inhibit? What is another drug with the same mechanism?
Mycophenolate and Ribavirin inhibit IMP (inosine monophosphate) dehydrogenase
What does Hydroxyurea inhibit?
Hydroxyurea inhibits ribonucleotide reductase
What does 6-MP inhibit? What is another drug with the same mechanism?
6-mercaptopurine (6-MP) and its prodrug Azathioprine inhibit de novo purine synthesis
What does 5-FU inhibit? What effect does this have?
5-fluorouracil (5-FU) inhibits thymidylate synthase (decrease deoxythymidine monophosphate [dTMP])
What does MTX inhibit, and in what kinds of organisms? What other 2 drugs have this same mechanism, and what kind of organisms do they affect?
Methotrexate (MTX), Trimethoprim (TMP), and Pyrimethamine inhibit dihydrofolate reductase (reduce dTMP) in humans, bacteria, and protozoa, respectively
Draw the interconnected purine salvage pathways, including and labeling where each of the following act: (1) HGPRT + PRPP (2) APRT + PRPP (3) Adenosine deaminase (ADA) (4) Xanthine oxidase.
See p. 68 in First Aid 2014 for visual at top of page
What are the molecular and functional effects of adenosine deaminase deficiency?
Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase => prevents DNA synthesis and thus decreased lymphocyte count
What is one of the major causes of autosomal recessive SCID?
Adenosine deaminase deficiency
What defect causes Lesch-Nyhan syndrome? Give the normal reactions that are affected. What molecular effect does this have?
Defective purine salvage due to absent HGPRT, which converts hypoxanthine to IMP and guanine to GMP; Results in excess uric acid production and de novo synthesis
What is the mode of inheritance of Lesch-Nyhan syndrome?
X-linked recessive
What are 6 clinical findings/symptoms of Lesch-Nyhan syndrome?
Findings: (1) intellectual disability, (2) self-mutilation, (3) aggression, (4) hyperuricemia, (5) gout, (6) dystonia.; Think: “HGPRT: Hyperuricemia, Gout, Pissed off (aggression, self-mutilation), Retardation (intellectual disability), dysTonia”
What defines the Unambiguous property of the genetic code?
Each codon species only 1 amino acid
What defines the Degenerate/Redundant property of the genetic code? What are the exceptions to this property?
Most amino acids are coded by multiple codons; Exceptions: Methionine and Tryptophan encoded by only 1 codon (AUG and UGG, respectively)
What defines the Commaless, Nonoverlapping property of the genetic code? What are the exceptions to this property?
Read from a fixed starting point as a continuous sequence of bases; Exceptions: some viruses
What defines the Universal property of the genetic code? What is the exception to this property?
Genetic code is conserved throughout evolution; Exception in humans: mitochondria
