Cell Respiration and Metabolism 123If there are more amino acids than are needed for protein
synthesis, the amine group from glutamic acid may be removed
and excreted as urea in the urine ( fig. 5.16 ). The metabolic path-
way that removes amine groups from amino acids—leaving a
keto acid and ammonia (which is converted to urea)—is known
as oxidative deamination.
A number of amino acids can be converted into glutamic
acid by transamination. Since glutamic acid can donate amine
groups to urea (through deamination), it serves as a channel
through which other amino acids can be used to produce keto
acids (pyruvic acid and Krebs cycle acids). These keto acids
may then be used in the citric acid cycle as a source of energy
( fig. 5.17 ).
Depending upon which amino acid is deaminated, the keto
acid left over may be either pyruvic acid or one of the Krebs
cycle acids. These can be respired for energy, converted to
fat, or converted to glucose. In the last case, the amino acids
are eventually changed to pyruvic acid, which is used to form
glucose. This process—the formation of glucose from amino
acids or other noncarbohydrate molecules—is called gluconeo-
genesis, as mentioned previously in connection with the Cori
cycle.
The main substrates for gluconeogenesis are the three-
carbon-long molecules of alanine (an amino acid), lac-
tic acid, and glycerol. This illustrates the interrelationship
between amino acids, carbohydrates, and fat, as shown in
figure 5.18.
Recent experiments in humans have suggested that, even
in the early stages of fasting, most of the glucose secreted by
the liver is derived through gluconeogenesis. Findings indicate
that hydrolysis of liver glycogen (glycogenolysis) contributes
only 36% of the glucose secreted during the early stages of a
fast. At 42 hours of fasting, all of the glucose secreted by the
liver is produced by gluconeogenesis.Uses of Different Energy Sources
The blood serves as a common trough from which all the cells
in the body are fed. If all cells used the same energy source,
such as glucose, this source would quickly be depleted and
cellular starvation would occur. Normally, however, the blood
contains a variety of energy sources from which to draw: glu-
cose and ketone bodies that come from the liver, fatty acids
from adipose tissue, and lactic acid and amino acids from
muscles. Some organs preferentially use one energy source
more than the others, so that each energy source is “spared” for
organs with strict energy needs.
The brain uses blood glucose as its major energy source.
Under fasting conditions, blood glucose is supplied primar-
ily by the liver through glycogenolysis and gluconeogenesis.
In addition, the blood glucose concentration is maintained
because many organs spare glucose by using fatty acids, ketone
bodies, and lactic acid as energy sources ( table 5.4 ). During
severe starvation, the brain also gains some ability to metabo-
lize ketone bodies for energy.Each transamination reaction is catalyzed by a specific
enzyme (a transaminase) that requires vitamin B 6 (pyridox-
ine) as a coenzyme. The amine group from glutamic acid, for
example, may be transferred to either pyruvic acid or oxalo-
acetic acid. The former reaction is catalyzed by the enzyme
alanine transaminase (ALT); the latter reaction is catalyzed by
aspartate transaminase (AST). These enzyme names reflect
the fact that the addition of an amine group to pyruvic acid pro-
duces the amino acid alanine; the addition of an amine group
to oxaloacetic acid produces the amino acid known as aspartic
acid ( fig. 5.15 ).
Oxidative Deamination
As shown in figure 5.16 , glutamic acid can be formed through
transamination by the combination of an amine group with
a -ketoglutaric acid. Glutamic acid is also produced in the
liver from the ammonia that is generated by intestinal bacte-
ria and carried to the liver in the hepatic portal vein. Because
free ammonia is very toxic, its removal from the blood and
incorporation into glutamic acid is an important function of a
healthy liver.
Figure 5.16 Oxidative deamination. Glutamic acid is
converted to a -ketoglutaric acid as it donates its amine group to
the metabolic pathway that results in the formation of urea.
α-Ketoglutaric acidGlutamic acidHHKeto acidAmino acid NH 3 + CO 2
NO
C N
HHHHUreaAmino transfer
Urea cycle in liverCLINICAL APPLICATION
Liver enzyme tests refer to measurements of the plasma
levels of the transaminase enzymes AST and ALT. High lev-
els of plasma AST and ALT result from acute viral hepatitis
A and B, an overdose of acetaminophen (Tylenol), or other
conditions that cause immediate damage to the liver cells.
However, the liver may be extensively damaged due to hep-
atitis C without a great rise in these transaminase enzymes.
Also, these enzymes are found in many tissues, and may be
elevated for causes other than liver disease. In particular,
plasma AST is elevated in heart or skeletal muscle disease.
AST and ALT do not actually measure liver function, which
is better assessed by coagulation measurements, plasma
albumin and bilirubin concentrations, and other tests.