Life Eze Plus with SAMe

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S-adenosylmethionine

• Important methyl-donating coenzyme
• Can also donate methylene groups, amino groups,
  ribosyl groups and aminopropyl groups
• Reactivity based on electrophilic nature of atoms
  surrounding S
• Tetrahydrofolate is another important methyl
  carrier
• Also important in initiating reractions by
  extracting H (i.e. H) via 5deoxyadenosyl
  radical
• Important but not well understood class of
  enzymes Radical SAM enzymes
• These reactions remind me very much of Vitamin
  B12-dependent reactions (which are usually
  rearrangements)
• Include ribonucleotide reductase
• Bioinformatics (based in part on C-X-X-X-C-X-X-C
  motif of unusual 3 Cys-liganded 4Fe4S center)
  indicates there are liekly hundreds of these
  proteins
• Low levels of folate can result in low levels of
  SAM (or SAMe) since folate is required for
  homocysteine ? methionine
• Not found in dietary sources (due to instability,
  Im pretty sure?), easily synthesized in us (when
  healthy)

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SAM or SAMe
SAH
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• Clinical uses have included
• Antidepressant (mechanism unknown)
• Treatment of neurological disorders ( )
• Antiosteoarthritis ( )
• Fibromyalgia ( )
• Treatment of liver disease
• Liver disease results in increase in blood
  methionine, less SAMe (etiology unknown), low
  levels of glutathione
• MAT enzyme seems to be involved (methionine
  adenosyl transferase, see overview)
• Parenteral and oral SAMe administration results
  in increased glutathione levels (and decreased
  methionine levels (?)

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The main parts of the SAMe cycle
Folate-dependent
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Vitamin B12

• R -CH3 (methylcobalamin) CN (cyanocobalamin,
  stable vitamin form), -Ad (adenosylcobalamin,
  active coenzyme)
• Catalyzes rearrangements
• One example methylmalonyl CoA mutase, which is
  important in breakdown of isoleucine, methionine,
  threonine, and valine as well as odd-chain fatty
  acids and cholesterol

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