section 17.1
Essential and Nonessential Amino Acids
339
n h
2
1
I
NH
N H ,
1
c = o
1
N H
A
a
A ,
r >
H ,N ^
C
Isonicotinic acid hydrazide
{antituberculosis drug)
Hydralazine
(hypertensive agent)
Cycloserine
(antibiotic)
FIGURE 17-6
Structures of compounds that inhibit pyridoxal phosphate-containing
enzymes.
of amino acids from tissue protein. After a meal, dietary
amino acids enter the plasma and replenish the tissues that
supply amino acid during fasting.
Liver
plays a major role, since it can oxidize all amino
acids except leucine, isoleucine, and valine (see Chap-
ter 22). It also produces the nonessential amino acids from
the appropriate carbon precursors. Ammonia formed in the
gastrointestinal tract or from various deaminations in the
liver is converted to urea and excreted in urine (discussed
later).
Skeletal muscle
tissue constitutes a large portion of the
body weight and accounts for a significant portion of non-
hepatic amino acid metabolism. It takes up the amino acids
required to meet its needs for protein synthesis, and me-
tabolizes alanine, aspartate, glutamate, and the branched-
chain amino acids. Amino acids are released from muscle
during the postabsorptive state (i.e., in fasting or starva-
tion). Alanine and glutamine constitute more than 50% of
the a-amino acid nitrogen released. During starvation, the
total amino acid pool increases from catabolism of con-
tractile proteins. However, the amino acid composition of
these proteins does not account for the large amount of ala-
nine and glutamine released. Amino acids that give rise to
pyruvate can be transaminated to alanine. For example,
aspartate can be converted to alanine as follows:
transaminase
PEPCK
Aspartate--------- ►
Oxaloacetate-----
pyruvate kinase
Phosphoenolpyruvate-----------
>
transaminase
Pyruvate---------
>
Alanine
Similarly, amino acids that produce tricarboxylic acid
(TCA) cycle intermediates (Chapter 15) produce alanine
by conversion to oxaloacetate. During starvation or in-
take of a carbohydrate-poor diet, conversion of pyruvate
to alanine is preferred because pyruvate dehydrogenase is
inactivated by oxidation of fatty acids and ketone bodies
(Chapters 13 and 18).
Glutamine is synthesized from glutamate and ammonia
by glutamine synthase:
C O C T
(C H
2 ) 2
CHNH3+
I
COO-
+ ATP‘l + NH4+ ---- ►
L -G lutam ate
CONH2
I
(CH2)2
|
+ ADP3~ +Pi2- +H +
CHNH3 +
I
COO"
L -G lutam ine
Glutamate is derived by transamination of a-keto-
glutarate produced in the TCA cycle from citrate via ox-
aloacetate and acetyl-CoA (Chapter 13). All of the amino
acids can produce acetyl-CoA. All except leucine and ly-
sine (which are oxidized solely to acetyl-CoA) can be used
in net synthesis of a-ketoglutarate to enhance glutamate
synthesis. Ammonia is generated in glutamate dehydro-
genase and AMP deaminase reactions (Chapter 21).
The mucosa of the
small intestine
metabolizes dietary
glutamine, glutamate, asparagine, and aspartate by oxida-
tion to CO
2
and H
2
O, or by conversion to lactate, alanine,
citrulline, and NH
3
. These intermediates and the unme-
tabolized dietary amino acids are transferred to the portal
blood and then to the liver for further metabolism.
In the fasting state, the intestinal mucosa depends on
other tissues for metabolites to provide energy and precur-
sors for protein and nucleotide synthesis to maintain the
rapid cell division characteristic of that tissue. Glutamine,
released from liver and muscle, is utilized for purine
nucleotide synthesis (Chapter 27), is oxidized to provide
energy, and can be converted to aspartate for pyrimidine
nucleotide synthesis (Chapter 27). Thus, glutamine is im-
portant in cells undergoing rapid division. Intestine can
also oxidize glucose, fatty acids, and ketone bodies to
provide energy.
Kidney
releases serine and small (but significant) quan-
tities of alanine into the blood, and takes up glutamine,
proline, and glycine. Amino acids filtered in the glomeruli
are reabsorbed by renal tubule cells. Glutamine plays an
important role in acid-base regulation by providing am-
monia, which forms the NHj ion eliminated in urine
(Chapter 39). It can provide two ammonia molecules, by
glutaminase and glutamate dehydrogenase, respectively,
in renal tubular mitochondria. Its carbon skeleton can
be oxidized or converted to glucose since renal tissue is
capable of gluconeogenesis (Chapter 15).
