Organic Chemistry

Section 10.11 Biological Methylating Reagents 395

group in each of these methylating agents is attached to a positively charged atom.
This means that the methyl groups are attached to very good leaving groups, so bio-
logical methylation can take place at a reasonable rate.

Biological systems use SAM to convert norepinephrine (noradrenaline) into epi-
nephrine (adrenaline). The reaction is a simple methylation reaction. Norepinephrine
and epinephrine are hormones that are released into the bloodstream in response to
stress. Epinephrine is the more potent hormone of the two.

The conversion of phosphatidylethanolamine, a component of cell membranes, into
phosphatidylcholine requires three methylations by three equivalents of SAM.
(Biological cell membranes will be discussed in Section 26.4; the use of
as a biological methylating agent is discussed in more
detail in Section 25.8.)

N^5 -methyltetrahydrofolate

norepinephrine

noradrenaline

epinephrine

adrenaline

NH 2

N

N

O

N

N

+

HO

OH

HO CHCH 2 NH 2

−O

2 CCHCH 2 CH 2 SCH 2

CH 3

NH 3

HO

OH

HO CHCH 2 NHCH 3 H+

H

OH

H

H H

OH

+

+

NH 2

N

N

O

N

N

−O

2 CCHCH 2 CH 2 SCH 2

NH 3

H

OH

H

H H

OH

+

N^5 -methyltetrahydrofolate

tetrahydrofolate

Nu ++NuCH 3

−

H 2 N

HN

O

N

N

HCH 3

CH 2 NHR

N

H

H 2 N

HN

O

N

N

H

CH 2 NHR

N

H

+

−

+ +

NH 2

N

N

O

N

N

−O
Nu 2 CCHCH 2 CH 2 S CH 2

CH 3

NH 3

H

OH

H

H H

OH

+

+

NH 2

N

N

O

N

N

−O

NuCH 3 2 CCHCH 2 CH 2 SCH 2

NH 3

H

OH

H

H H

OH

+

S-adenosylmethionine

SAM

S-adenosylhomocysteine

SAH

RCO

O

O 3 SAM

O−

O

CH 2 OCR

CH 2 OPOCH 2 CH 2 NH 2

CH RCO

O

O

O− CH 3

O

CH 2

CH 3

OCR

CH 2 OPOCH 2 CH 2 NCH 3

CH

phosphatidylethanolamine phosphatidylcholine

+ + 3 SAH

+