336
chapter 17
Protein and Amino Acid Metabolism
glycine. The reaction for glycine is analogous to that for
D-amino acids.
H
3
N — C — C O O "
I
H
G lycin e
D-Amino acid
oxidase
~7
\ ’
FAD
FADH2
H202
02
H
I
+ H
2
N = C — C O O '
a -lm in o a c id
H jO
H
I
0 = C — C O O '
G lyoxylate
D-Amino acid oxidase occurs in peroxisomes contain-
ing other enzymes that produce H
2
O
2
(e.g., L-a-hydroxy
acid oxidase, citrate dehydrogenase, and L-amino acid ox-
idase) and catalase and peroxidase, which destroy H
2
O
2
.
In leukocytes, killing of bacteria involves hydrolases of
lysosomes and production of H
2
O
2
by NADPH oxidase
(Chapter 15). Conversion of D-amino acids to the corre-
sponding a-keto acids removes the asymmetry at the
a-
carbon atom. The keto acids may be aminated to L-amino
acids. By this conversion from D- to L-amino acids, the
body utilizes D-amino acids derived from the diet:
R
1
o-Amino acid
1
oxidase
H— c — N H 3+ ----------------------- >
I
C O O '
o-A m in o a c id (n o t
u sefu l for p rotein
sy n th e sis)
R
C = 0
R eanim ation
(transaminase)
Nonoxidative deamination
is accomplished by several
specific enzymes.
Amino acid dehydratases deaminate hydroxyamino
acids:
S p rin p
1
Specific
HjO
o e rtn e
I
dehydratase #
T h re o n in e >
---------------------
*—
H o m o serin e J
(Pyftdoxal phosphate)
NH3
a -lm in o
— S
- — ►
a-K eto
a c id
a cid
For serine dehydratase the reaction is
H20
H O — C H
2
— C H — C O O ' ----- ^ — >H
2
C = C — C O O '
NH 3 +
N H 3 +
S erin e
O
H
3
C — C — C O O '
P yru vate
H20
- ^ - H 3C—C—COO“
NH3
1
n h 2 +
Dehydrogenation o f -Glutamate
Glutamate dehydrogenase
plays
a major role in
amino acid metabolism. It is a zinc protein, requires
NAD+ or NADP+ as coenzyme, and is present in high
concentrations in mitochondria of liver, heart, muscle, and
kidney. It catalyzes the (reversible) oxidative deamination
of L-glutamate to a-ketoglutarate and NH3. The initial
step probably involves formation of a-iminoglutarate by
dehydrogenation. This step is followed by hydrolysis of
the imino acid to a keto acid and NH3:
H
I
'O O C — C H
2
— C H
2
— C — C O O ' + N A D (P )+
N H 3+
L -G lu tam ate
C O O '
a -K eto a c id (h a s n o
a sy m m etric a -c a r b o n )
R
O O C — C H
2
— C H
2
— C — C O O ' + N A D (P )H + H +
II
n h 2 +
a -lm in o g lu ta ric a cid
+ H
3
N — C — H
H20 > x»H20
C O O '
L-A m ino a cid
(m eta b o lica lly u sefu l)
O O C — C H
2
— C H
2
— C — C O O ' + N H 4 +
II
0
a -K eto g lu ta ra te
