section 17.1
Essential and Nonessential Amino Acids
337
Glutamate dehydrogenase is an allosteric protein mod-
ulated positively by ADP, GDP, and some amino acids and
negatively by ATP, GTP, and NADH. Its activity is affected
by thyroxine and some steroid hormones
in vitro.
Gluta-
mate dehydrogenase is the only amino acid dehydroge-
nase present in most cells. It participates with appropriate
transaminases (aminotransferases) in the deamination of
other amino acids.
N A D (P)H + NH„ +
■ N A D (P )+ + H 20
pyridoxal phosphate
enzyme
These reactions are at near-equilibrium, so their over-
all effect depends upon concentrations of the substrates
and products. Aminotransferases occur in cytosol and mi-
tochondria, but their activity is much higher in cytosol.
Since glutamate dehydrogenase is restricted to mitochon-
dria, transport of glutamate (generated by various transam-
inases) into mitochondria by a specific carrier becomes of
central importance in amino acid metabolism. The NH3
produced in deamination reactions must be detoxified by
conversion to glutamine and asparagine or to urea, which
is excreted in urine. The NADH generated is ultimately
oxidized by the electron transport chain.
Transamination
Transamination
reactions combine reversible amina-
tion and deamination, and they mediate redistribution of
amino groups among amino acids. Transaminases (amino-
transferases) are widely distributed in human tissues and
are particularly active in heart muscle, liver, skeletal mus-
cle, and kidney. The general reaction of transamination is
C O O “
cocr
C O O “
coo~
1
HC— NH3+
1
I
+ C = 0
|
Transaminase
^
-
---------------------- ►
n
----n
J_
I
HC— IMH
3
|
(pyridoxal phosphate)
>
R,
r
2
R,
r
2
A m ino acid
K eto acid
K eto acid
A m ino a cid
(1)
(
2
)
(
1
)
(
2
)
The a-ketoglutarate/L-glutamate couple serves as an
amino group acceptor/donor pair in transaminase reac-
tions. The specificity of a particular transaminase is for
the amino group other than the glutamate. Two transami-
nases whose activities in serum are indices of liver damage
catalyze the following reactions:
L-Glutamate
a-Ketoglutarate
Glutamate-pyruvate
transaminase (GPT) or
alanine aminotransferase (ALT)
+
«
~
=
*
+
Pyruvate
L -A lan in e
L-Giutamate
a-Ketoglutarate
Glutamate-pyruvate
transaminase (GPT) or
alanine aminotransferase (ALT)
+
<
—
+
Oxaloacetate
L-Aspartate
All of the amino acids except lysine, threonine, proline,
and hydroxyproline participate in transamination reac-
tions. Transaminases exist for histidine, serine, pheny-
lalanine, and methionine, but the major pathways of
their metabolism do not involve transamination. Transam-
ination of an amino group not at the «-position can
also occur. Thus, transfer of 5-amino group of ornithine
to G'-ketoglutarate converts ornithine to glutamate-y-
semialdehyde.
All transaminase reactions have the same mechanism
and use pyridoxal phosphate (a derivative of vitamin B6;
Chapter 38). Pyridoxal phosphate is linked to the enzyme
by formation of a Schiff base between its aldehyde group
and the
s
-amino group of a specific lysyl residue at the
active site and held noncovalently through its positively
charged nitrogen atom and the negatively charged phos-
phate group (Figure 17-3). During catalysis, the amino
acid substrate displaces the lysyl e-amino group of the en-
zyme in the Schiff base. An electron pair is removed from
the a-carbon of the substrate and transferred to the posi-
tively charged pyridine ring but is subsequently returned
F IG U R E 1 7 -3
Binding of pyridoxal phosphate to its apoenzyme. The carbonyl carbon
reacts with the £-amino group of the lysyl residue near the active site to
yield a Schiff base. Ionic interactions involve its positively charged
pyridinium ion and negatively charged phosphate group.
