section 17.3
Metabolism of Some Individual Amino Acids
353
acids is necessary to monitor the degree of dietary restric-
tion and patient compliance.
Many aminoacidurias and their metabolites give rise
to abnormal odors, maple syrup urine disease is one ex-
ample. Some of the others are
p h e n y lk e to n u ria
(musty
odor),
tyro sin em ia typ e I
(boiled cabbage),
g lu ta ric
a cid u ria
(sweaty feet),
3 -m e th y lc ro to n y lg ly c in u ria
(cat’s
urine), and
trim eth yla m in u ria
(fish). In patients with
trimethylaminuria the compound responsible for the fish
odor is trimethylamine which is a byproduct of protein
catabolism by the large intestinal bacterial flora. Normally,
trimethylamine is inactivated by hepatic flavin monooxy-
genases. Several different mutations in the gene for flavin
monooxygenases have been identified in trimethylamin-
uric patients. An inhibitor of flavin monooxygenases is
indole-3-carbinol found in dark green vegetables (e.g.,
broccoli). The amelioration of symptoms of bad odor in
trimethylaminuria may be achieved by limiting intake of
dark green vegetables and protein, and by administering
low doses of antibiotics to reduce intestinal bacterial flora.
Sulfur-Containing Amino Acids
M eth io n in e
and cysteine are the principal sources of or-
ganic sulfur in humans. Methionine is essential (unless
adequate homocysteine and a source of methyl groups are
available), but cysteine is not, since it can be synthesized
from methionine.
Adenosine— S— (CH2^—CH— COOH
I
CH3
S-Adenosylmethionine
NH2
Adenosine— S— (CH2)— CH— COOH
S-Adenosylhomocysteine
Specific methyltransferase
7
Acceptor (examples)
Acceptor — CH3 (examples)
1
. Guanidinoacetic acid
2. Nicotinamide
3. Norepinephrine
4. Phosphatidylethanolamine
5. N-Acetyl-serotonin
1
. Creatine
2. N-Methylnicotinamide
3. Epinephrine
4. Phosphatidylcholine
(three cycles of methylation)
5. Melatonin
FIGURE 17-15
Selected methyl transfer reactions involving S-adenosylmethionine.
The methyl group is transferred to appropriate accep-
tors by specific methyltransferases with production of
S-adenosylhomocysteine (Figure 17-15), which is hy-
drolyzed to homocysteine and adenosine by adenosylho-
mocysteinase:
NH3 +
NH3+
I
H20
Adenosine
I
Adenosyl— S— (CH2)2— CH— C O O "------ ^ — *2--------->
HS— (CH2)2— CH— COO
S-Adenosythomocysteine
Homocysteine
Homocysteine
can be recycled back to
methionine
either by transfer of a methyl group from betaine catalyzed
by betaine-homocysteine methyltransferase, or from N5-
methyltetrahydrofolate (N
5
-methyI-FH
4
) catalyzed by N
5
-
methyl-FH
4
-methyltransferase, which requires methyl
cobalamin:
M eth io n in e
Methionine is utilized primarily in protein synthe-
sis, providing sulfur for cysteine synthesis, and is the
body’s principal methyl donor. In methylation reactions,
S-adenosylmethionine (SAM) is the methyl group donor.
SAM is a sulfonium compound whose adenosyl moiety is
derived from ATP as follows:
N H 3+
I
ATP. H20
PP, + P,
C H
3
— S — (C H
2
)
2
— C H — C O O
----------^ ------- *£ -------------------- ►
Methionine adenosyltransferase
M eth ion ine
ui
N H 3+
I
H S— (C H
2
)
2
— C H — C O O " + (C H 3)3+ N - C H 2—
coo
Betaine-homocysteine
methyltransferase
Hom ocysteine
Betaine
N H
3
+
I
H
3
C — S— (C h
2
)
2
— C H — C O O " + (C H
3
)
2
N — C H
2
— C O O "
M ethionine
Dim ethylglycine
(2)
N H 3+
I
H S— (C H
2
)
2
— C H — C O O
+
N 5— M ethyl— FH
4
N5-Methyi-FH,-homocysteine
methyltransferase
(methylcobalamin)
N H 3+
I
H
3
C — S— (C H
2
)
2
— C H — C O O " +
f h
4
N H 3+
I
" O O C — C H — (C H
2)2
B eta in e
(an acid) is obtained from oxidation of choline
(an alcohol) in two steps:
FAD
FADHj
(C H
3
)
3
+ N — C H
2
— C H 2O H — ^
^
— ►
(C H 3) 3+ N — C H 2— C H O
Choline oxidase
C h oline
B etain e aldeh yd e
NAD*
—
Betaine aldehyde
dehydrogenase
S-A d enosylm ethio nin e
(active m ethionine)
(C H
3
)
3
N — C H 2— C O O “
B etaine
