User:Kia Yang/sandbox: Difference between revisions

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This page is being worked on during the Spring 2022 semester.

~~Methionine is an essential amino acid required by our bodies for healthy cell and tissue growth. Methionine is not naturally derived, and is obtained from our diet in the form of homocysteine.~~ '''Methionine synthase''' (abbrev. MS; EC: 2.1.1.13), a B12-dependent enzyme, is a critical part of the one-carbon metabolism cycle. It ~~catalyzes~~ the ~~methylation~~ of homocysteine to methionine. MS mutations and B-12 deficiencies are associated with serious health conditions such as birth abnormalities and anemia.

'''Methionine synthase''' (abbrev. MS; EC: 2.1.1.13) is a B12-dependent enzyme that catalyzes the methylation of homocysteine to methionine. This enzyme is a critical part of the one-carbon metabolism cycle as methionine is an essential amino acid required by our bodies for healthy cell and tissue growth. It is not naturally derived in our bodies, thus requiring the conversion of homocysteine, obtained from our diet, to methionine. MS mutations and B-12 deficiencies are associated with serious health conditions such as birth abnormalities and anemia.

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[[Image:Overall.jpeg]]

The change from homocysteine to methionine is an SN2 reaction, as seen above, where the methyl group on N-5 from methyltetrahydrofolate (MTHF), is donated. MTHF is a product of ~~Methylenetetrahydrofolate~~ reductase (MTHFR) from the folate cycle [link Shaylie's page here]. This is a complex reaction as tetrahydrofolate, the product, is a poor leaving group and ~~thus requiring~~ a "super nucleophile", vitamin B12 ~~cob~~(I)alamin, to carry out the reaction<ref name="Kung et al">DOI: 10.1038/nature10916</ref>; the methyl carrier.

The change from homocysteine to methionine is an SN2 reaction, as seen above, where the methyl group on N-5 from methyltetrahydrofolate (MTHF), is donated. MTHF is a product of methylenetetrahydrofolate reductase (MTHFR) from the folate cycle [link Shaylie's page here]. This is a complex reaction as tetrahydrofolate (THF), the product, is a poor leaving group and requires a "super nucleophile", vitamin B12 Cob(I)alamin, to carry out the reaction<ref name="Kung et al">DOI: 10.1038/nature10916</ref>; the methyl carrier.

MS undergoes two cycles: catalytic and reductive reactivation cycles.

Catalytic Cycle:

Cob(I)alamin is required in order to carry through with the complex SN2 reaction of breaking the bond between THF and the methyl group.

Co(I) - reactive but unstable, high energy

Reactivation Cycle:

In aerobic conditions, Cob(I)alamin occasionally undergoes oxidation leading to an inactive Cob(II)alamin enzyme. This is regulated by reductive methylation to ctivate Cob(I)alamin with Flavodoxin as an electron donor, and subsequently regenerating Me-Cob(I)alamin with SAM as the methyl donor.

== Relevance ==

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Catalytic Cycle:

Cobalt in the +1 oxidation state is required in order to carry through with the complex SN2 reaction of breaking the bond between THF and the methyl group.

~~Co(I) - reactive but unstable, high energy~~

Reactivation Cycle:

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 This page is being worked on during the Spring 2022 semester.
-Methionine is an essential amino acid required by our bodies for healthy cell and tissue growth. Methionine is not naturally derived, and is obtained from our diet in the form of homocysteine. '''Methionine synthase''' (abbrev. MS; EC: 2.1.1.13), a B12-dependent enzyme, is a critical part of the one-carbon metabolism cycle. It catalyzes the methylation of homocysteine to methionine. MS mutations and B-12 deficiencies are associated with serious health conditions such as birth abnormalities and anemia.
+'''Methionine synthase''' (abbrev. MS; EC: 2.1.1.13) is a B12-dependent enzyme that catalyzes the methylation of homocysteine to methionine. This enzyme is a critical part of the one-carbon metabolism cycle as methionine is an essential amino acid required by our bodies for healthy cell and tissue growth. It is not naturally derived in our bodies, thus requiring the conversion of homocysteine, obtained from our diet, to methionine. MS mutations and B-12 deficiencies are associated with serious health conditions such as birth abnormalities and anemia.
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 [[Image:Overall.jpeg]]
-The change from homocysteine to methionine is an SN2 reaction, as seen above, where the methyl group on N-5 from methyltetrahydrofolate (MTHF), is donated. MTHF is a product of Methylenetetrahydrofolate reductase (MTHFR) from the folate cycle [link Shaylie's page here]. This is a complex reaction as tetrahydrofolate, the product, is a poor leaving group and thus requiring a "super nucleophile", vitamin B12 cob(I)alamin, to carry out the reaction<ref name="Kung et al">DOI: 10.1038/nature10916</ref>; the methyl carrier.
+The change from homocysteine to methionine is an SN2 reaction, as seen above, where the methyl group on N-5 from methyltetrahydrofolate (MTHF), is donated. MTHF is a product of methylenetetrahydrofolate reductase (MTHFR) from the folate cycle [link Shaylie's page here]. This is a complex reaction as tetrahydrofolate (THF), the product, is a poor leaving group and requires a "super nucleophile", vitamin B12 Cob(I)alamin, to carry out the reaction<ref name="Kung et al">DOI: 10.1038/nature10916</ref>; the methyl carrier.
+MS undergoes two cycles: catalytic and reductive reactivation cycles.
+Catalytic Cycle:
+Cob(I)alamin is required in order to carry through with the complex SN2 reaction of breaking the bond between THF and the methyl group.
+Co(I) - reactive but unstable, high energy
+Reactivation Cycle:
+In aerobic conditions, Cob(I)alamin occasionally undergoes oxidation leading to an inactive Cob(II)alamin enzyme. This is regulated by reductive methylation to ctivate Cob(I)alamin with Flavodoxin as an electron donor, and subsequently regenerating Me-Cob(I)alamin with SAM as the methyl donor.
 == Relevance ==
@@ Line 33: / Line 44: @@
 Catalytic Cycle:
 Cobalt in the +1 oxidation state is required in order to carry through with the complex SN2 reaction of breaking the bond between THF and the methyl group.
-Co(I) - reactive but unstable, high energy
 Reactivation Cycle: