Catabolism of amino acids
Amino acid catabolism
does occur in plants, but its
purpose is to produce
metabolites for other
biosynthetic pathways. In
animals, amino acids
undergo oxidative
degradation in three
different metabolic
circumstances:
1. During the normal
synthesis and degradation
of cellular proteins, some
amino acids that are
released from protein
breakdown and are not
needed for new protein
synthesis undergo
oxidative degradation.
2. When a diet is rich in
protein and the ingested
amino acids exceed the
body’s needs for protein
synthesis, the surplus is catabolized; amino acids cannot be stored.
3. During starvation or in uncontrolled diabetes mellitus, when carbohydrates are either
unavailable or not properly utilized, cellular proteins are used as fuel.
Under all these metabolic conditions, amino acids lose their amino groups to form α-keto acids,
the “carbon skeletons” of amino acids. The α-keto acids undergo oxidation to CO2 and H2O or,
often more importantly, provide three- and four-carbon units that can be converted by
gluconeogenesis into glucose, the fuel for brain, skeletal muscle, and other tissues.
Metabolic fate of amino groups
Amino acids derived from dietary protein are the source of most amino groups. Most amino
acids are metabolized in the liver. Some of the ammonia generated in this process is recycled
and used in a variety of biosynthetic pathways; the excess is either excreted directly or
converted to urea or uric acid for excretion, depending on the organism. Excess ammonia
generated in other (extrahepatic) tissues travels to the liver (in the form of amino groups) for
conversion to the excretory form.
Glutamate and glutamine play especially critical roles in nitrogen metabolism, acting as a kind
of general collection point for amino groups. In the cytosol of hepatocytes,
amino groups from most amino acids are transferred to α-ketoglutarate to form
glutamate, which enters mitochondria and gives up its amino group to form
NH4 –. Excess ammonia generated in most other tissues is converted to the
amide nitrogen of glutamine, which passes to the liver, then into liver
mitochondria.
, Glutamine or glutamate or both are present in higher concentrations than other amino acids in
most tissues. In skeletal muscle, excess amino groups are generally transferred to pyruvate to
form alanine, another important molecule in the transport of amino groups to the liver.
1. Dietary Protein Is Enzymatically Degraded to Amino Acids
In humans, the degradation of ingested proteins to their constituent amino acids occurs in the
gastrointestinal tract. Entry of dietary protein into the stomach stimulates the gastric mucosa to
secrete the hormone gastrin, which in turn stimulates the secretion of hydrochloric acid by the
parietal cells and pepsinogen by the chief cells of the gastric glands. The acidic gastric juice
(pH 1.0 to 2.5) is both an antiseptic, killing most bacteria and other foreign cells, and a
denaturing agent, unfolding globular proteins and rendering their internal peptide bonds more
accessible to enzymatic hydrolysis. Pepsinogen, an inactive precursor, or zymogen, is
converted to active pepsin by the enzymatic action of pepsin itself. In the stomach, pepsin
hydrolyzes ingested proteins at peptide bonds on the amino-terminal side of the aromatic amino
acid residues Phe, Trp, and Tyr, cleaving long polypeptide chains into a mixture of smaller
peptides.
As the acidic stomach contents pass into the small intestine, the low pH triggers secretion of
the hormone secretin into the blood. Secretin stimulates the pancreas to secrete bicarbonate
into the small intestine to neutralize the gastric HCl, abruptly increasing the pH to about 7. The
digestion of proteins now continues in the small intestine. Arrival of amino acids in the upper
part of the intestine (duodenum) causes release into the blood of the hormone cholecystokinin,
which stimulates secretion of several pancreatic enzymes with activity optima at pH 7 to 8.
Trypsinogen, chymotrypsinogen, and procarboxypeptidases A and B, the zymogens of
trypsin, chymotrypsin, and carboxypeptidases A and B, are synthesized and secreted by the
exocrine cells of the pancreas. Trypsinogen is converted to its active form, trypsin, by
enteropeptidase, a proteolytic enzyme secreted by intestinal cells. Free trypsin then catalyzes
the conversion of additional trypsinogen to trypsin. Trypsin also activates chymotrypsinogen,
the procarboxypeptidases, and proelastase.
Synthesis of the enzymes as inactive precursors protects the exocrine cells from destructive
proteolytic attack. The pancreas further protects itself against self-digestion by making a
specific inhibitor, a protein called pancreatic trypsin inhibitor, that effectively prevents
premature production of active proteolytic enzymes within the pancreatic cells.
Trypsin and chymotrypsin further hydrolyze the peptides that were produced by pepsin in the
stomach. This stage of protein digestion is accomplished very efficiently, because pepsin,
trypsin, and chymotrypsin have different amino acid specificities. Degradation of the short
peptides in the small intestine is then completed by other intestinal peptidases such as
carboxypeptidases A and B (both of which are zinc-containing enzymes), which remove
successive carboxyl-terminal residues from peptides, and an aminopeptidase that hydrolyzes
successive amino-terminal residues from short peptides.
The resulting mixture of free amino acids is transported into the epithelial cells lining the small
intestine, through which the amino acids enter the blood capillaries in the villi and travel to the
liver. In humans, most globular proteins from animal sources are almost completely hydrolyzed
to amino acids in the gastrointestinal tract, but some fibrous proteins, such as keratin, are only
partly digested. In addition, the protein content of some plant foods is protected against
breakdown by indigestible cellulose husks.
Amino acid catabolism
does occur in plants, but its
purpose is to produce
metabolites for other
biosynthetic pathways. In
animals, amino acids
undergo oxidative
degradation in three
different metabolic
circumstances:
1. During the normal
synthesis and degradation
of cellular proteins, some
amino acids that are
released from protein
breakdown and are not
needed for new protein
synthesis undergo
oxidative degradation.
2. When a diet is rich in
protein and the ingested
amino acids exceed the
body’s needs for protein
synthesis, the surplus is catabolized; amino acids cannot be stored.
3. During starvation or in uncontrolled diabetes mellitus, when carbohydrates are either
unavailable or not properly utilized, cellular proteins are used as fuel.
Under all these metabolic conditions, amino acids lose their amino groups to form α-keto acids,
the “carbon skeletons” of amino acids. The α-keto acids undergo oxidation to CO2 and H2O or,
often more importantly, provide three- and four-carbon units that can be converted by
gluconeogenesis into glucose, the fuel for brain, skeletal muscle, and other tissues.
Metabolic fate of amino groups
Amino acids derived from dietary protein are the source of most amino groups. Most amino
acids are metabolized in the liver. Some of the ammonia generated in this process is recycled
and used in a variety of biosynthetic pathways; the excess is either excreted directly or
converted to urea or uric acid for excretion, depending on the organism. Excess ammonia
generated in other (extrahepatic) tissues travels to the liver (in the form of amino groups) for
conversion to the excretory form.
Glutamate and glutamine play especially critical roles in nitrogen metabolism, acting as a kind
of general collection point for amino groups. In the cytosol of hepatocytes,
amino groups from most amino acids are transferred to α-ketoglutarate to form
glutamate, which enters mitochondria and gives up its amino group to form
NH4 –. Excess ammonia generated in most other tissues is converted to the
amide nitrogen of glutamine, which passes to the liver, then into liver
mitochondria.
, Glutamine or glutamate or both are present in higher concentrations than other amino acids in
most tissues. In skeletal muscle, excess amino groups are generally transferred to pyruvate to
form alanine, another important molecule in the transport of amino groups to the liver.
1. Dietary Protein Is Enzymatically Degraded to Amino Acids
In humans, the degradation of ingested proteins to their constituent amino acids occurs in the
gastrointestinal tract. Entry of dietary protein into the stomach stimulates the gastric mucosa to
secrete the hormone gastrin, which in turn stimulates the secretion of hydrochloric acid by the
parietal cells and pepsinogen by the chief cells of the gastric glands. The acidic gastric juice
(pH 1.0 to 2.5) is both an antiseptic, killing most bacteria and other foreign cells, and a
denaturing agent, unfolding globular proteins and rendering their internal peptide bonds more
accessible to enzymatic hydrolysis. Pepsinogen, an inactive precursor, or zymogen, is
converted to active pepsin by the enzymatic action of pepsin itself. In the stomach, pepsin
hydrolyzes ingested proteins at peptide bonds on the amino-terminal side of the aromatic amino
acid residues Phe, Trp, and Tyr, cleaving long polypeptide chains into a mixture of smaller
peptides.
As the acidic stomach contents pass into the small intestine, the low pH triggers secretion of
the hormone secretin into the blood. Secretin stimulates the pancreas to secrete bicarbonate
into the small intestine to neutralize the gastric HCl, abruptly increasing the pH to about 7. The
digestion of proteins now continues in the small intestine. Arrival of amino acids in the upper
part of the intestine (duodenum) causes release into the blood of the hormone cholecystokinin,
which stimulates secretion of several pancreatic enzymes with activity optima at pH 7 to 8.
Trypsinogen, chymotrypsinogen, and procarboxypeptidases A and B, the zymogens of
trypsin, chymotrypsin, and carboxypeptidases A and B, are synthesized and secreted by the
exocrine cells of the pancreas. Trypsinogen is converted to its active form, trypsin, by
enteropeptidase, a proteolytic enzyme secreted by intestinal cells. Free trypsin then catalyzes
the conversion of additional trypsinogen to trypsin. Trypsin also activates chymotrypsinogen,
the procarboxypeptidases, and proelastase.
Synthesis of the enzymes as inactive precursors protects the exocrine cells from destructive
proteolytic attack. The pancreas further protects itself against self-digestion by making a
specific inhibitor, a protein called pancreatic trypsin inhibitor, that effectively prevents
premature production of active proteolytic enzymes within the pancreatic cells.
Trypsin and chymotrypsin further hydrolyze the peptides that were produced by pepsin in the
stomach. This stage of protein digestion is accomplished very efficiently, because pepsin,
trypsin, and chymotrypsin have different amino acid specificities. Degradation of the short
peptides in the small intestine is then completed by other intestinal peptidases such as
carboxypeptidases A and B (both of which are zinc-containing enzymes), which remove
successive carboxyl-terminal residues from peptides, and an aminopeptidase that hydrolyzes
successive amino-terminal residues from short peptides.
The resulting mixture of free amino acids is transported into the epithelial cells lining the small
intestine, through which the amino acids enter the blood capillaries in the villi and travel to the
liver. In humans, most globular proteins from animal sources are almost completely hydrolyzed
to amino acids in the gastrointestinal tract, but some fibrous proteins, such as keratin, are only
partly digested. In addition, the protein content of some plant foods is protected against
breakdown by indigestible cellulose husks.
