• Life Eze Plus with SAMe• GET YOUR LIFE BACK! If you suffer from low mood, mild anxiety, stress or

nervous tension then you may need LifeEZE Plus. • LifeEZE Plus has a calming effect on the mind, enabling you to think more

clearly and keeping you in a positive frame of mind. • AT LAST! One of Europe’s biggest selling supplements for lifting mood,

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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 5’deoxyadenosyl 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, I’m pretty sure?), easily

synthesized in us (when healthy)

N

HC

NN

CH

N

NH2

HC

HC CH

CH

OH2C S+

CH3

CH2 CH2 CH

-O2C

NH3+

OH HO

SAM or SAMe

N

HC

NN

CH

N

NH2

HC

HC CH

CH

OH2C S CH2 CH2 CH

-O2C

NH3+

OH HO

SAH

• 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 (?)

The main parts of the “SAMe cycle”

Folate-dependent

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

=CoIII

H2C Ad

CoIII

H2C Ad

R CH2 R

+

CoII

H2C Ad

R CH R

+

CoII

H3C Ad

CoIII

HC RRH3C Ad