Nucleotide_Metabolism

Consult textbook on page 893 methylmaloyl coa

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Unformatted text preview: will be shown in the next slide, the only way to convert N5 ­ methyltetrahydrofolate back to tetrahydrofolate is to transfer the N5 methyl group to coenzyme B12, a reac0on catalyzed by methionine synthase. Why does deficiency of vitamin B12 and folate both lead to anemia? Methyl group in N5 ­methyltetrahydrofolate is involved in synthesis of methionine and S ­ adenosylmethionine (SAM), a common methyl group donor. The only way to convert N5 ­ methyltetrahydrofolate back to tetrahydrofolate is through methionine synthase. Deficiency of vitamin B12 or folate can result in anemia, although of different types. Discussion session is a paper on megablobas0c anemia. Ribonucleo0de reductase catalyzes reduc0on of ribonucleo0des to deoxyribonucleo0des for DNA synthesis. Cataly0c mechanism involves a radical. One of the first and perhaps the best known examples of radical forma0on in biological systems. Radical genera0on is ini0ated by a tyrosyl radical close to the ac0ve site. How does a radical stabilize carboca0on? Answer: Hyperconjuga0on http://chemwiki.ucdavis.edu/ Follow the electrons in ribonucleo0de reductase reac0on: Source of electrons for reduc0on is NADPH through thioredoxin. What is the source of NADPH? Which pathway supplies NADPH? dCTP and dUTP serve as precursors of thymidylate (dTMP) to be used in DNA synthesis. Thymidylate synthase catalyzes methyla0on of dUMP to synthesize dTMP. The methyl group is donated from N5,N10 ­methylene ­tetrahydrofolate. Why would synthesis of dTMP become affected in megaloblas0c anemia? (subject of discussion session) What 0ssues in the body undergo heavy DNA synthesis? Folate is vitamin B9. Different oxidized and reduced forms of folate serve as methyl or formyl donor groups in nucleo0de synthesis. (Make sure you see the difference between formyl vs. methyl.) As will be shown in the next slide, the only way to convert N5 ­ methyltetrahydrofolate back to tetrahydrofolate is to transfer the N5 methyl group to coenzyme B12, a reac0on catalyzed by methionine synthase. Why does deficiency of vitamin B12 and folate both lead to anemia? The thymidylate pathway is a major target of an0 ­microbial and an0 ­cancer treatments. Methotrexate binds dihydrofolate reductase (DHFR) with about 1,000 ­fold higher affinity than dihydrofolate. DHFR structure is stabilized by binding to MTX, a phenomenon used to determine protein import into mitochondria back in one of the discussion sessions earlier in the semester. Why are cancer cells more suscep0ble to inhibi0on of nucleo0de biosynthe0c pathways? What other types of normal cells are affected?...
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