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CASE FILES: BIOCHEMISTRY
transamination, the carbon skeleton is oxidatively metabolized as an energy
source during situations such as sustained exercise and caloric insufficiency.
The amino group is transported in the circulation to the liver as either glutamine
(formed by the enzymatic addition of an amino group to the side-chain group
of glutamate) or alanine (formed by enzymatic transfer of the a-amino group
from glutamate to pyruvate). Once at the liver, the transferred amino groups are
ultimately used in urea synthesis, as described above (see Figure 39-2).
In contrast to skeletal muscle, which is the primary site of endogenous gluta-
mine synthesis, rapidly dividing cells (e.g., lymphocytes, enterocytes) prefer-
entially use glutamine. The reason for this is that rapidly dividing cells
require both energy as well as precursors for biosynthetic reactions. The carbon
skeleton of glutamine enters intermediary metabolism via a-ketoglutarate,
a Krebs cycle intermediate, providing the required energy for cellular
processes. In addition, the amino groups of glutamine are used in purine and
pyrimidine biosynthesis, which in turn are required for the synthesis of both
ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). Indeed, lympho-
cyte proliferation is greatly accelerated when glutamine is used as a metabolic
substrate (as opposed to glucose), leading to suggestions that glutamine defi-
ciency may result in immunosuppression and therefore increased susceptibil-
ity to infection. An additional reason for high rates of glutamine utilization in
enterocytes appears to be for the synthesis of citrulline. The latter is trans-
ported to the kidney, where it is converted to arginine. Arginine is not only
important in protein synthesis but also essential in cellular signaling (via nitric
oxide production) and in maintaining adequate levels of urea cycle intermedi-
ates (Figure 39-3).
Glutamine also plays an important role in maintenance of whole body
acid-base balance. High rates of catabolism of positively charged and sulfur-
containing amino acids result in the net formation of hydrogen ions. To main-
tain an acid-base balance, the kidney uses glutamine as a gluconeogenic
precursor, resulting in glucose, bicarbonate (HCO-) ion, and ammonium
(NH4+) ion formation. The bicarbonate is released into the circulation, where
it associates with a proton (forming CO
2
and H
2
O), thereby increasing blood
pH. In contrast, the ammonium ion is excreted (see Figure 39-3).
As noted above, amino acids are not only used for protein synthesis but are
also essential for the biosynthesis of other biomolecules. These include carni-
tine (a derivative of lysine); creatine (a derivative of glycine and arginine); glu-
tathione (a derivative of glutamate, cysteine, and glycine); serotonin and
melatonin (derivatives of tryptophan); dopamine, norepinephrine, and epi-
nephrine (derivatives of tyrosine); as well as purines and pyrimidines (requir-
ing aspartate and glutamine for biosynthesis). Alterations in dietary intake of
amino acids can influence the rates at which these macromolecules are syn-
thesized. For example, ingestion of a tryptophan-rich meal elevates neuronal
serotonin synthesis, resulting in lethargy. Tryptophan crosses the blood-brain
barrier via a transporter that is also specific for the branched-chain amino
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