Amino Acid Catabolism:
Unlike fats and carbohydrates, amino acids are not stored by the body, that is, no protein exists whose sole function is
to maintain a supply of amino acids for future use. Therefore, amino acids must be obtained from the diet, synthesized
de novo, or produced from normal protein degradation. Any amino acids in excess of the biosynthetic needs of the cell
are rapidly degraded.
Amino acids undergo catabolism under 3 different metabolic circumstances
1. During normal synthesis and degradation of cellular proteins, any amino acids that are not recycled will be
oxidised to yield ATP. Some amino acids that are not needed for new protein synthesis undergo oxidative
degredation.
2. Dietary protein surplus is catabolised –oxidised to yield ATP as amino acids cannot be stored.
3. During starvation or in uncontrolled diabetes mellitus, when carbohydrates are either unavailable or not
properly used, cellular proteins will be oxidised to yield ATP/cellular proteins used as fuel under these
circumstances.
The first phase of catabolism involves the removal of the α-amino groups (usually by transamination and subsequent
oxidative deamination), forming ammonia and the corresponding α-keto acid—the “carbon skeletons” of amino acids.
A portion of the free ammonia is excreted in the urine, but most is used in the synthesis of urea (Figure 19.1), which is
quantitatively the most important route for disposing of nitrogen from the body.
In the second phase of amino acid catabolism, described in Chapter 20, the carbon skeletons of the
α-keto acids are converted to common intermediates of energy producing, metabolic pathways. These compounds can
be metabolized to CO2 and water or can provide 3 and 4-C units that can be converted by gluconeogenesis into
glucose to fuel the brain, skeletal muscles or other tissues or into fatty acids, or ketone bodies by the central pathways
of metabolism. They can also be converted to new amino acids.
The amino groups and the carbon skeleton
therefore, take different but interrelated pathways.
As only a few organisms can convert N2 to a
biologically useful form, NH3 is carefully
husbanded in biological systems. Amino acids
derived from dietary proteins are the main source
of amino groups. Most amino acids are
metabolised in the liver. Some of the ammonia
generated in this process is recycled and the excess
is excreted wither directly or is converted to urea
for excretion depending on the organism. Excess
ammonia generated in extra-hepatic tissues travels
to the liver in the form of amino groups for
conversion to the excretory form. GLUTAMATE,
GLUTAMINE, ALANINE AND ASPARTATE
have central roles in N metabolism as they are the
ones most easily converted to citric acid cycle
intermediates.
Nitrogen Metabolism:
Amino acid catabolism is part of the larger process of the metabolism of nitrogen-containing molecules. Nitrogen
enters the body in a variety of compounds present in food, the most important being amino acids contained in dietary
protein. Nitrogen leaves the body as urea, ammonia, and other products derived from amino acid metabolism. The role
of body proteins in these transformations involves two important concepts:
, The amino acid pool and protein turnover.
A. Amino acid pool
Free amino acids are present throughout the body, for example, in cells,
blood, and the extracellular fluids. For the purpose of this discussion,
envision all these amino acids as if they belonged to a single entity,
called the amino acid pool. This pool is supplied by three sources:
1) amino acids provided by the degradation of body proteins,
2) amino acids derived from dietary protein, and
3) synthesis of nonessential amino acids from simple intermediates of
metabolism.
Conversely, the amino pool is depleted by three routes:
1) synthesis of body protein,
2) amino acids consumed as precursors of essential nitrogen-containing
small molecules, and
3) conversion of amino acids to glucose, glycogen, fatty acids, ketone
bodies, or CO2 + H2O.
Although the amino acid pool is small (comprised of about 90–100 g of
amino acids) in comparison with the amount of protein in the body
(about 12 kg in a 70-kg man), it is conceptually at the center of whole-
body nitrogen metabolism.
In healthy, well-fed individuals, the input to the amino acid pool is
balanced by the output, that is, the amount of amino acids contained in
the pool is constant. The amino acid pool is said to be in a steady state,
and the individual is said to be in nitrogen balance.
B. Protein turnover
Most proteins in the body are constantly being synthesized and then
degraded, permitting the removal of abnormal or unneeded proteins. For
many proteins, regulation of synthesis determines the concentration of
protein in the cell, with protein degradation assuming a minor role. For
other proteins, the rate of synthesis is constitutive, that is, relatively
constant, and cellular levels of the protein are controlled by selective
degradation.
In healthy adults, the total amount of protein in the body remains
constant, because the rate of protein synthesis is just sufficient to
replace the protein that is degraded. This process, called protein
turnover, leads to the hydrolysis and resynthesis of 300–400 g of body
protein each day. The rate of protein turnover varies widely for individual
proteins. Shortlived proteins (for example, many regulatory proteins and
misfolded proteins e.g. P53) are rapidly degraded, having halflives
measured in minutes or hours. Longlived proteins, with halflives of
days to weeks, constitute the majority of proteins in the cell. Structural
proteins, such as collagen, are metabolically stable, and have halflives
measured in months or years.
There are two major enzyme systems responsible for degrading damaged or unneeded proteins: the ATPdependent
ubiquitinproteasome system of the cytosol, and the ATPindependent degradative enzyme system of the lysosome.
Proteasomes degrade mainly endogenous proteins, that is, proteins that were synthesized within the cell. Lysosomal
enzymes (acid hydrolases, see p. 162) degrade primarily extracellular proteins, such as plasma proteins that are
taken into the cell by endocytosis, and cellsurface membrane proteins that are used in receptormediated
endocytosis.
The individual degredation rates of proteins vary within a single organelle or cell compartment and also from
compartment to compartment due either to differing sensitivity to local proteasomes or differing rates of transfer to the
cytosol or lysosomes. The range of protein degredation within a single organelle is also limited suggesting that the
proteins may be treated as groups or families.
Unlike fats and carbohydrates, amino acids are not stored by the body, that is, no protein exists whose sole function is
to maintain a supply of amino acids for future use. Therefore, amino acids must be obtained from the diet, synthesized
de novo, or produced from normal protein degradation. Any amino acids in excess of the biosynthetic needs of the cell
are rapidly degraded.
Amino acids undergo catabolism under 3 different metabolic circumstances
1. During normal synthesis and degradation of cellular proteins, any amino acids that are not recycled will be
oxidised to yield ATP. Some amino acids that are not needed for new protein synthesis undergo oxidative
degredation.
2. Dietary protein surplus is catabolised –oxidised to yield ATP as amino acids cannot be stored.
3. During starvation or in uncontrolled diabetes mellitus, when carbohydrates are either unavailable or not
properly used, cellular proteins will be oxidised to yield ATP/cellular proteins used as fuel under these
circumstances.
The first phase of catabolism involves the removal of the α-amino groups (usually by transamination and subsequent
oxidative deamination), forming ammonia and the corresponding α-keto acid—the “carbon skeletons” of amino acids.
A portion of the free ammonia is excreted in the urine, but most is used in the synthesis of urea (Figure 19.1), which is
quantitatively the most important route for disposing of nitrogen from the body.
In the second phase of amino acid catabolism, described in Chapter 20, the carbon skeletons of the
α-keto acids are converted to common intermediates of energy producing, metabolic pathways. These compounds can
be metabolized to CO2 and water or can provide 3 and 4-C units that can be converted by gluconeogenesis into
glucose to fuel the brain, skeletal muscles or other tissues or into fatty acids, or ketone bodies by the central pathways
of metabolism. They can also be converted to new amino acids.
The amino groups and the carbon skeleton
therefore, take different but interrelated pathways.
As only a few organisms can convert N2 to a
biologically useful form, NH3 is carefully
husbanded in biological systems. Amino acids
derived from dietary proteins are the main source
of amino groups. Most amino acids are
metabolised in the liver. Some of the ammonia
generated in this process is recycled and the excess
is excreted wither directly or is converted to urea
for excretion depending on the organism. Excess
ammonia generated in extra-hepatic tissues travels
to the liver in the form of amino groups for
conversion to the excretory form. GLUTAMATE,
GLUTAMINE, ALANINE AND ASPARTATE
have central roles in N metabolism as they are the
ones most easily converted to citric acid cycle
intermediates.
Nitrogen Metabolism:
Amino acid catabolism is part of the larger process of the metabolism of nitrogen-containing molecules. Nitrogen
enters the body in a variety of compounds present in food, the most important being amino acids contained in dietary
protein. Nitrogen leaves the body as urea, ammonia, and other products derived from amino acid metabolism. The role
of body proteins in these transformations involves two important concepts:
, The amino acid pool and protein turnover.
A. Amino acid pool
Free amino acids are present throughout the body, for example, in cells,
blood, and the extracellular fluids. For the purpose of this discussion,
envision all these amino acids as if they belonged to a single entity,
called the amino acid pool. This pool is supplied by three sources:
1) amino acids provided by the degradation of body proteins,
2) amino acids derived from dietary protein, and
3) synthesis of nonessential amino acids from simple intermediates of
metabolism.
Conversely, the amino pool is depleted by three routes:
1) synthesis of body protein,
2) amino acids consumed as precursors of essential nitrogen-containing
small molecules, and
3) conversion of amino acids to glucose, glycogen, fatty acids, ketone
bodies, or CO2 + H2O.
Although the amino acid pool is small (comprised of about 90–100 g of
amino acids) in comparison with the amount of protein in the body
(about 12 kg in a 70-kg man), it is conceptually at the center of whole-
body nitrogen metabolism.
In healthy, well-fed individuals, the input to the amino acid pool is
balanced by the output, that is, the amount of amino acids contained in
the pool is constant. The amino acid pool is said to be in a steady state,
and the individual is said to be in nitrogen balance.
B. Protein turnover
Most proteins in the body are constantly being synthesized and then
degraded, permitting the removal of abnormal or unneeded proteins. For
many proteins, regulation of synthesis determines the concentration of
protein in the cell, with protein degradation assuming a minor role. For
other proteins, the rate of synthesis is constitutive, that is, relatively
constant, and cellular levels of the protein are controlled by selective
degradation.
In healthy adults, the total amount of protein in the body remains
constant, because the rate of protein synthesis is just sufficient to
replace the protein that is degraded. This process, called protein
turnover, leads to the hydrolysis and resynthesis of 300–400 g of body
protein each day. The rate of protein turnover varies widely for individual
proteins. Shortlived proteins (for example, many regulatory proteins and
misfolded proteins e.g. P53) are rapidly degraded, having halflives
measured in minutes or hours. Longlived proteins, with halflives of
days to weeks, constitute the majority of proteins in the cell. Structural
proteins, such as collagen, are metabolically stable, and have halflives
measured in months or years.
There are two major enzyme systems responsible for degrading damaged or unneeded proteins: the ATPdependent
ubiquitinproteasome system of the cytosol, and the ATPindependent degradative enzyme system of the lysosome.
Proteasomes degrade mainly endogenous proteins, that is, proteins that were synthesized within the cell. Lysosomal
enzymes (acid hydrolases, see p. 162) degrade primarily extracellular proteins, such as plasma proteins that are
taken into the cell by endocytosis, and cellsurface membrane proteins that are used in receptormediated
endocytosis.
The individual degredation rates of proteins vary within a single organelle or cell compartment and also from
compartment to compartment due either to differing sensitivity to local proteasomes or differing rates of transfer to the
cytosol or lysosomes. The range of protein degredation within a single organelle is also limited suggesting that the
proteins may be treated as groups or families.
