Excess nitrogen is excreted primarily as urea (Chapter 17).
Since nitrogen is essential but cannot be stored, the body
attempts to maintain “nitrogen balance.” In positive nitro-
gen balance, more nitrogen is ingested than is eliminated.
This occurs during growth, pregnancy, lactation, and re-
covery from trauma, such as major surgery. If less nitrogen
is ingested than is excreted, the body is in negative nitrogen
balance. In times when dietary nitrogen is not available,
negative nitrogen balance occurs because some nitrogen
is always excreted as urea and ammonia.
Of the 20 amino acids in proteins, the body can readily
synthesize eight if an appropriate nitrogen source is avail-
able. Two others can be synthesized from other amino
acids of the diet: tyrosine from phenylalanine and cys-
teine from methionine. The rest must be provided in the
diet (Chapter 17), since the body can synthesize none or
an insufficient amount. The dietary requirement depends
on several factors. Beside essential amino acids, the diet
should provide the nitrogen required for synthesis of the
nonessential amino acids.
Ammonia Toxicity
Ammonia, a metabolite formed from many nitrogen-
containing compounds, is used for biosynthesis. High am-
monia levels are toxic. The energy requirements of the
brain, which is sensitive to high levels of ammonia, are
met almost exclusively by glucose oxidation, for which a
source of oxaloacetate is essential. This condition is sat-
isfied by the carboxylation of pyruvate, even though the
pyruvate carboxylase is somewhat limiting. For efficient
TCA cycle activity, considerable recycling of oxaloacetate
is necessary, since
de novo
synthesis is limited. With high
levels of ammonia, the equilibrium for glutamate dehy-
drogenase favors formation of glutamate and glutamine,
which diminishes the ammonia level but decreases TCA
cycle activity. The brain is thus deprived of its source of
ATP generation. In addition, glutamate and aspartate have
neurotransmitter functions.
Within the liver, elimination of ammonia occurs via urea
synthesis (Chapter 17). Since urea is uncharged, it does not
disturb the acid-base balance. Many interorgan relation-
ships in protein and nitrogen homeostasis arose because
of the role that the liver plays in excess nitrogen excretion.
Nitrogen Transfer between Compounds
and Tissues
Nitrogen is eliminated from the body as urea and ammonia.
Urea synthesized in the liver is excreted by the kidneys.
Urinary ammonia is produced in the kidney. The nitrogen
in other tissues is transported to the liver and kidney in
section 22.7
Protein Synthesis and Nitrogen Homeostasis
the form of amino acids. The general reactions involved
in these processes are described below.
Methods for Directly Transferring Nitrogen
Nitrogen for biosynthetic processes is derived from the
o'-amino group of amino acids and from the amido group of
glutamine and asparagine by transamination and transami-
dation, respectively (Chapter 17). Because of the wide
variety of transaminases, transamination can provide the
right balance of all nonessential amino acids and nitrogen-
containing compounds derived from them. Transamida-
tion is less ubiquitous. Other reactions utilizing the nitro-
gen of amino acids include the incorporation of glycine
into purines and its partial incorporation into porphyrins.
Reactions in Which Ammonia Is Released
Ammonia is produced by oxidative and nonoxidative
deaminations catalyzed by glutaminase and glutamate de-
hydrogenase (Chapter 17). Ammonia is also released in the
purine nucleotide cycle. This cycle is prominent in skeletal
muscle and kidney. Aspartate formed via transamination
donates its a-amino group in the formation of AMP; the
amino group is released as ammonia by the formation of
IMP.
Reactions That “Fix” Ammonia
In
muscle,
ammonia is used to synthesize other
nitrogen-containing compounds or is eliminated. In ei-
ther case, glutamine and glutamate are formed by glu-
tamine synthetase and glutamate dehydrogenase, respec-
tively. The glutamate dehydrogenase reaction is readily
reversible, but that of glutamine synthetase is not because
it is driven by the hydrolysis of ATP. Glutamine synthesis
is the major mechanism for nonhepatic tissues to eliminate
ammonia. In liver, ammonia is fixed by the formation of
urea (Chapter 17).
Disposition of Dietary Intake of Protein
Ingested protein is digested in a stepwise fashion in the
stomach, small intestinal lumen, and small intestinal mu-
cosal cells (Chapter 12). Peptides formed in the intestinal
lumen are absorbed into the mucosal cells and degraded
to free amino acids. The outflow of amino acids to the
portal vein does not reflect the amino acid composition
of the ingested protein. Thus, alanine levels increase two-
to fourfold, and glutamine, glutamate, and aspartate are
absent. These changes arise from amino acid interconver-
sions within the intestinal cell.
With the exception
of the branched-chain
amino
acids (valine, leucine, and isoleucine), most amino acids
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