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December 9-10, 2009
AMINO ACID METABOLISM I,II,III
Lecturer: Eileen M. Lafer
Reading: Stryer Edition 6: Chapters 23 and 24
OBJECTIVES:
1.
Understand the fates and sources of the amino acids in general terms.
2.
Understand the general features of lysosomal protein degradation,
including what types of proteins are degraded in lysosomes.
3.
Understand how "controlled proteolysis" is effected in cells. This
includes an understanding of the mechanism of selection and attachment of
ubiquitin to target proteins, as well as where and how ubiquitinated proteins are
degraded.
4.
Understand the common pathways for the removal of the a-amino
group from an a-amino acid during amino acid catabolism.
5.
Understand how the fate of the ammonium ions generated during
amino acid degradation differs in the liver versus the peripheral tissues.
6.
Understand the fundamentals of the urea cycle and how it is regulated.
Understand how defective urea cycle enzymes can lead to disease, and how
those diseases are treated.
7.
Understand which a-amino acid carbon skeletons feed into which major
metabolic intermediates during amino acid catabolism.
8.
Know which amino acids are solely ketogenic, solely glucogenic, and
both ketogenic and glucogenic.
9.
Know which steps in amino acid degradation lead to the following
diseases: methyl-malonic acedemia, homocystinuria, maple syrup disease,
phenylketonuria, tyrosinemia I, II and III, and alkaptonuria. For each disease,
you should know the name of the defective enzyme, the reaction catalyzed by
the enzyme, and the pathway in which the enzyme functions.
10.
Know which amino acids are essential and which are non-essential in
humans.
11.
Know in humans, which major metabolic intermediates are able to
serve as carbon skeletons for the biosynthesis of which amino acids.
12.
Know which amino acids can act as neurotransmitters.
13.
Know which amino acids can be used for the synthesis of which
neurotransmitters.
14.
Understand in general terms the biosynthesis of spermine, spermidine,
creatine and phosphocreatine.
SOURCES AND FATES
OF AMINO ACIDS IN THE BODY
PROTEIN CATABOLISM
Proteolysis of
dietary proteins
in the stomach
and lumen of the
small intestine
releases free
amino acids into
the bloodstream.
Proteolysis of
proteins that
move through
the endocytic
pathway takes
place in the
lysosomes of
all cells.
Controlled
proteolysis of
ubiquitin-tagged
intracellular
proteins takes
place in the
proteasomes of
all cells.
AMINO ACID POOL
LYSOSOMAL DEGRADATION
1. Lysosomes degrade proteins taken up by
endocytosis, or proteins that traffic within the endocytic
pathway.
2.
Lysosomes contain ~50 hydrolytic enzymes
(proteases). Their pH optima is acidic.
3.
The pH of the lysosome is ~5.
4.
In well-nourished cells, lysosomal protein
degradation is non-selective.
5.
In starving cells, there is a selective pathway
that preferentially degrades cytosolic proteins containing
the pentapeptide KFERQ (Lys-Phe-Glu-Arg-Gln).
CONTROLLED PROTEOLYSIS
1.
Ubiquitin tags proteins for destruction.
2. The proteasome digests the ubiquitin
tagged proteins.
3. Protein degradation can be used to
regulate biological function.
UBIQUITIN
The Mark of Death
76 aa polypeptide.
C-terminal gly attaches
to the e-amino groups of
several lys on a protein
destined for
degradation.
Additional ubiquitin
molecules can be
added to Lys48.
UBIQUITIN CONJUGATION
E1=Ubiquitin-Activating Enzyme
E2=Ubiquitin-Conjugating Enzyme
E3=Ubiquitin-Protein Ligase
UBIQUITIN IS
ATTACHED
TO THE
e-AMINO GROUP
OF LYSINE
RESIDUES ON
TARGET
PROTEINS
CLINICAL CORRELATION:
Human papilloma virus (HPV)
encodes a protein that activates a
specific E3 enzyme. The enzyme
ubiquitinates the tumor suppressor
p53 and other proteins that control
DNA repair, which are then
destroyed. The activation of this E3
enzyme is observed in more than
90% of all cervical carcinomas.
A SINGLE UBIQUITIN
MOLECULE IS A POOR
SIGNAL FOR
DEGRADATION.
CHAINS OF 4 OR
MORE UBIQUITIN
MOLECULES ARE
VERY STRONG
SIGNALS FOR
DEGRADATION.
WHAT DETERMINES WHETHER A
PROTEIN IS UBIQUITINATED?
The substrate specificity of each E3.
1. The N-terminal rule: the chemical nature of
the amino-terminal amino acid.
For example, a protein with methionine at it s N terminus has a half life of 20 hours, while a
protein with an arginine at its N-terminus has a half life of 2 minutes.
2. Cyclin destructive boxes: specific amino acid
sequences that mark cell-cycle proteins for
destruction.
3. PEST sequences: proteins rich in proline,
glutamic acid, serine and threonine.
THE 26S PROTEASOME DIGESTS
THE UBIQUITIN TAGGED PROTEINS
19S regulatory subunit
20S proteasome
(catalytic activity)
19S regulatory subunit
The Executioner
THE 20S PROTEASOME
1. 700kD, 28 homologous subunits:
14 of type a and 14 of type b.
2. Subunits are arranged in 4 rings of 7
subunits each to form a sealed barrel.
7
7
7
7
PROTEOLYTIC ACTIVITY RESIDES
IN THE N-TERMINALTHREONINE
RESIDUES OF THE BETA SUBUNITS
7
7
7
7
ACCESS TO THE 20S PROTEASOME
IS CONTROLLED BY THE 19S CAPS
The 19S
regulatory
subunits
bind to
polyubiquitin
chains.
SOURCES AND FATES
OF AMINO ACIDS IN THE BODY
PROTEIN DEGRADATION CAN
REGULATE BIOLOGICAL PROCESSES
Dynamically alter the stablity of regulatory proteins.
SOURCES AND FATES
OF AMINO ACIDS IN THE BODY
AMINO ACID DEGRADATION
1. Any amino acids generated by
protein catabolism that are not needed as
building blocks for new biomolecular
synthetic reactions are degraded to
carbon skeletons in the liver.
2. The first step in amino acid
degradation is the removal of nitrogen.
a-AMINO GROUPS ARE
CONVERTED INTO AMMONIUM
IONS BY OXIDATIVE DEAMINATION
OF GLUTAMATE
The a-amino group of the a-amino acid is transferred
to a-ketoglutarate to form glutamate, which is
oxidatively deaminated to yield ammonium ion.
1. THE TRANSAMINATION
REACTION: Aminotransferases (also called
transaminases) catalyze the transfer of an a-amino
group from an a-amino acid to an a-keto acid.
These enzymes generally utilize a-ketoglutarate as the
acceptor.
The enzymes are named after their amino acid
substrates, i.e. aspartate transaminase catalyzes
the transfer of the a-amino group of aspartate to aketoglutarate, yielding oxaloacetate plus glutamate.
2. THE OXIDATIVE DEAMINATION
REACTION: The nitrogen atom that is transferred
to a-ketoglutarate in the transamination reaction is
converted into free ammonium ion by oxidative
deamination.
This reaction is catalyzed by glutamate
dehydrogenase. This reaction takes place in the
mitochondria, and is driven by the consumption of
ammonia.
Dehydrogenation
Hydrolysis
The sum of the aminotransferase and glutamate
dehydrogenase reactions yield ammonium ion:
aminotransferase
AMINO ACID 1
ALPHA KETOACID 1
dehydrogenase
urea cycle
ALPHA KETOACID 2
AMINO ACID 2
excreted
ALL
AMINOTRANSFERASES
CONTAIN THE
PROSTHETIC GROUP
PYRIDOXAL
PHOSPHATE (PLP)
PLP is derived from
Pyridoxine
(Vitamin B6)
PLP TAUTOMERS:
The phenolic hydroxyl
group is slightly acidic,
favoring deprotonation.
The pyridine ring is slightly basic, which
favors protonation of the pyrimidine N.
PHENOLATE
PLP FORMS SCHIFF BASE
INTERMEDIATES IN
AMINOTRANSFERASES
AMINO ACID 1
(schiff-base linkage with the enzyme)
(schiff-base linkage with the substrate)
The positively charged schiff-base linkages are
stabilized by the negatively charged phenolate group.
TRANSAMINATION MECHANISM
1. The schiff base loses a proton from the a-carbon of
the amino acid to become a quinonoid intermediate.
2. Reprontonation of the quinonoid at the aldehyde
carbon yields a ketimine intermediate.
3. The ketimine is then hydrolyzed to an a-ketoacid
and PMP.
ALPHA KETOACID 1
1
2
3
ONCE THE AMINO GROUP HAS BEEN TRANSFERRED TO
PMP, PMP TRANSFERS THE AMINO GROUP TO ANOTHER
ALPHA-KETOACID BY REVERSING THE REACTION SCHEME
WE JUST DISCUSSED (FOLLOW THE RED ARROWS):
ALPHA KETOACID 2
(ALPHA KETOGLUTARATE)
3
2
4
AMINO ACID 2
(GLUTAMATE)
1
The sum of the aminotransferase and glutamate
dehydrogenase reactions yield ammonium ion:
aminotransferase
AMINO ACID 1
ALPHA KETOACID 1
dehydrogenase
urea cycle
ALPHA KETOACID 2
AMINO ACID 2
excreted
ASPARTATE AMINOTRANSFERASE
Active site Arg386
helps orient substrates
by binding to their
a-carboxylate groups.
PLP is bound to active site
Lys268 by a Schiff-base linkage.
MECHANISM OF THE
AMINOTRANSFERASE REACTION:
MOVIE:
Movie file 18-01.avi
• End of First Lecture
The sum of the aminotransferase and glutamate
dehydrogenase reactions yield ammonium ion:
aminotransferase
AMINO ACID 1
ALPHA KETOACID 1
dehydrogenase
urea cycle
ALPHA KETOACID 2
AMINO ACID 2
excreted
SERINE AND THREONINE
CAN BE DIRECTLY
DEAMINATED
1. The nitrogen atoms of MOST
amino acids are transferred to aketoglutarate.
2. The a-amino groups of serine
and threonine can be directly
converted into ammonium ion by the
action of dehydratases.
Threonine
a-ketobutyrate + NH4+
PERIPHERAL TISSUES
TRANSPORT NITROGEN TO THE
LIVER BY THE ALANINE CYCLE OR
AS GLUTAMINE
If amino acids are produced in tissues
that lack the urea cycle, they need a
mechanism to release nitrogen in a
form that can be absorbed by the
liver and converted into urea.
EXAMPLE: Muscle uses amino acids as
fuel during prolonged exercise and fasting.
THE ALANINE CYCLE
1. In peripheral tissues,the a-amino groups of the amino acids are transferred
to glutamate by a transamination reaction, as in the liver.
2. However, rather than oxidatively deaminating glutamate to form ammonium
ion, the a-amino group is transferred to pyruvate to form alanine.
3. The liver takes up the alanine, and converts it back to pyruvate by another
transamination reaction.
4. The pyruvate can be used for gluconeogenesis, and the amino group
eventually ends up as urea by the usual pathway.
a-ketoglutarate
pyruvate
a-ketoglutarate
glutamate
NITROGEN CAN ALSO BE
TRANSPORTED AS GLUTAMINE
Glutamine Synthetase:
NH4+ + glutamate + ATP
glutamine + ADP + Pi
Once glutamine is in the liver, it can be metabolized like any
other amino acid and the nitrogen can end up in the urea cycle.
SOURCES AND FATES
OF AMINO ACIDS IN THE BODY
IN LIVER THE
AMMONIUM
IONS
GENERATED
DURING
AMINO ACID
DEGRADATION
FEED INTO THE
UREA CYCLE
Urea cycle: importance
• NH4+ is a product of the breakdown of amino acids.
• NH4+ is required by cells for synthesis of nitrogencontaining compounds.
• Excess NH4+ is very toxic. Normal levels in human
blood are: [NH4+] < 70 M.
• Excess NH4+ is converted to urea via the urea cycle and
excreted. The urea cycle accounts of ~80% of the
excreted nitrogen.
Urea cycle: location and source of
atoms
• Urea synthesis takes place
mostly in the liver.
• One N atom of urea comes
from Asp (blue).
• One N atom comes from
NH4+ (green).
• One C atom comes from
CO2 (red).
• Ornithine acts as a carrier of
various atoms in the process
of synthesizing urea.
Urea cycle reactions: carbamoyl
phosphate synthetase
• Catalyzes formation of carbamoyl phosphate from
H2O, 2 ATPs, CO2 and NH3+.
• The positive heterotropic activator, Nacetylglutamate, is required for activity.
• Brings one C atom and one N atom into the urea cycle
as a carbamoyl group.
• Catalyzes the critical step in removing NH4+ from the
blood.
Urea cycle reactions: carbamoyl
phosphate synthetase
• The reaction is made irreversible by cleaving two ATP
molecules to two ADP.
• One molecule of phosphate is released while the second
phosphate ends up as part of carbamoyl phosphate.
Urea cycle reactions: carbamoyl
phosphate synthetase
• Carbamoyl phosphate synthetase is present at very high
concentration in the mitochondrial matrix (~1 mM).
• The high enzyme concentration allows the enzyme to
work well below the Km ~ 250 M for NH4+.
• By operating well below Km, a small increase in NH4+
leads to a large increase in the rate of removal of NH4+
insuring that NH4+ remains low.
Urea cycle reactions: ornithine
transcarbamoylase
• Catalyzes the formation of citrulline and Pi from
ornithine and carbamoyl phosphate.
• Transfer of a carbamoyl group to ornithine is facilitated
by rupture of a high energy phosphoanhydride bond.
• Catalyzes introduction of one C atom and one N atom
into the urea cycle from carbamoyl phosphate.
Urea cycle reactions: argininosuccinate
synthetase
• Catalyzes condensation of citrulline and aspartate to form
argininosuccinate.
• Catalyzes the introduction of one N atom into the urea
cycle from aspartate.
Urea cycle reactions: argininosuccinase
• Cleaves argininosuccinate to arginine and fumarate.
• Completes the transfer of the amino group from aspartate
to make arginine.
• Retains the carbon skeleton of aspartate (as a fumarate
molecule).
Urea cycle reactions: arginase
• Catalyzes hydrolysis of arginine to ornithine and urea.
• Ornithine “cycles” back to the first step and picks up
another carbamoyl group from carbamoyl phosphate.
Urea cycle: overall reaction
• PPi  2 Pi quickly in a
reaction catalyzed by
pyrophosphotase.
• Overall, four high energy
phosphate bonds are
broken to synthesize each
molecule of urea.
Urea cycle and the citric acid cycle
General amino
acid catabolism
• Fumarate production connects the urea cycle and the citric acid cycle
(fumarate  malate  oxaloacetate).
• In the citric acid cycle fumarate is converted to oxaloacetate.
• Oxaloacetate is transaminated to aspartate.
• Aspartate carries the amino groups of other amino acids into the urea
cycle.
Compartmentalization
of the
cycle
• Takes
placeurea
in the liver.
• Two intracellular locations.
• Mitochondrial matrix:
carbamoyl phosphate
formation and citrulline
synthesis.
• Cytosol: argininosuccinate
formation; cleavage of
argininosuccinate to
arginine and fumarate;
hydrolysis of arginine to
ornithine and urea.
Regulation of the urea cycle
• The urea cycle removes excess NH4+ which comes from the
breakdown of dietary amino acids.
• Overall control of the urea cycle is by enzyme levels, which
change by as much as ten-fold depending on the diet.
• The flow of compounds through the urea cycle also depends
on the concentrations of cycle intermediates.
• Several reactions convert amino acids into urea cycle
intermediates.
• Arginine from the diet can be converted to ornithine.
• Glutamate can be converted to ornithine by intestinal
enzymes.
Regulation of the urea cycle
• Fine control of the urea cycle is through regulation of
carbamoyl phosphate synthetase.
• N-acetylglutamate is a heterotropic allosteric activator of
carbamoyl phosphate synthetase. (Heterotropic means an
effector molecule that is different from the substrate.)
Regulation of the urea cycle
• N-acetylglutamate acts as a signal for high amino acid
concentrations.
• N-acetylglutamate is synthesized in the liver from acetylCoA and glutamate in a reaction catalyzed by Nacetylglutamate synthetase.
Regulation of the urea cycle
• The steady state concentration of N-acetylglutamate is
determined by two factors.
• Concentrations of substrates: acetyl CoA and glutamate.
• Concentration of arginine, which activates Nacetylglutamate synthetase.
Defective urea cycle enzymes and
inherited disease
• High NH4+ is toxic and a complete lack of any urea cycle
enzyme is fatal.
• Some diseases are believed to be due to partially active
defective enzymes.
• Defective enzymes cause high levels of NH4+ in the blood.
• Sometimes a low protein diet can help. The diet decreases
the amount of NH4+ that needs to be eliminated through
the urea cycle.
Defective enzymes and treatment
• Problem: argininosuccinase deficiency.
• Treatment: a low protein diet high in
arginine.
• Result: argininosuccinate is secreted in
place of urea.
X
Defective enzymes and treatment
• Problem: carbamoyl phosphate synthetase or ornithine
transcarbamoylase deficiency.
• Result: glycine and glutamine build up (pyruvate and
glutamate accept amino groups from ammonium ions).
Defective enzymes and treatment
• Treatment: feed benzoate to remove Gly as hippurate.
• Treatment: feed phenylacetate to remove Gln as
phenylacetylglutamine.
+
NH4 toxicity and excess glutamine
• NH4+ toxicity may be due to formation of excess glutamine.
• High glutamine levels are found in the cerebrospinal fluid of
those with high NH4+.
• High glutamine and glutamate may lead to brain damage,
possibly by producing osmotic effects that cause brain swelling.
+
NH4 toxicity and excess glutamine
• Treatment: a low protein diet high in arginine.
• Result: argininosuccinate is secreted in place of urea.
feed
excreted
Urea cycle: overall reaction
• PPi  2 Pi quickly in a
reaction catalyzed by
pyrophosphotase.
• Overall, four high energy
phosphate bonds are
broken to synthesize each
molecule of urea.
Hyperammonemia:
Why is NH4+ toxic?
a-ketoglutarate + NH4+ <---> Glutamate + NH4+ <---> Glutamine
Excess Glutamate and Glutamine lead to osmotic effects, i.e. brain
swelling; Exitatory Amino Acid Neurotoxicity
SOURCES AND FATES
OF AMINO ACIDS IN THE BODY
FATES OF THE CARBON
SKELETONS OF THE AMINO ACIDS
1. The strategy of amino acid degradation
is to transform the carbon skeletons into
major metabolic intermediates that can
be converted into glucose, or oxidized by
the citric acid cycle.
2. The carbon skeletons of a diverse set
of 20 amino acids are funneled into only 7
molecules: pyruvate, acetyl CoA,
acetoacetyl CoA, a-ketoglutarate,
succinyl CoA, fumarate and
oxaloacetate.
PYRUVATE AS AN ENTRY POINT
INTO METABOLISM
3-carbon
amino acids
ala, ser, cys
enter via
pyruvate.
OXALOACETATE AS AN ENTRY
POINT INTO METABOLISM
The skeletons
of 4-carbon
amino acids
enter at
oxaloacetate.
a-KETOGLUTARATE AS AN ENTRY
POINT INTO METABOLISM
The skeletons of several 5-carbon amino acids enter
the TCA cycle at a-ketoglutarate. All first transfer their
amino groups to glutamate, which is then oxidatively
deaminated by glutamate dehydrogenase to yield
a-ketoglutarate.
SUCCINYL COENZYME A AS AN
ENTRY POINT INTO METABOLISM
FOR SEVERAL NON-POLAR
AMINO ACIDS
Threonine
(in humans)
CLINICAL
CORRELATION:
methyl-malonic
acedemia
methylmalonylCoA mutase is
defective
CLINICAL
CORRELATION:
homocystinuria
Scoliosis, muscle weakness,
mental retardation, thin
blond hair
cystathione
b-synthase is
defective
Glucogenic Amino Acids: amino acids (aa) that are converted to metabolites
that can be converted to glucose. TCA cycle intermediates and pyruvate can
be converted to phosphoenolpyruvate and then glucose.
Ketogenic Amino Acids: aa that give rise to ketone bodies or fatty acids.
Only leucine and lysine
are solely ketogenic.
Isoleucine,phenylalanine,
tryptophan and tyrosine
are both ketogenic and
glucogenic.
Remaining 14
amino acids are
solely glucogenic.
WHEN THE BRANCHED CHAIN
AMINO ACIDS VALINE, ISOLEUCINE,
AND LEUCINE ARE DEGRADED IN
EXTRA-HEPATIC TISSUES THEY
SHARE TWO COMMON ENZYMES:
branched-chain aminotransferase
branched-chain a-ketoacid dehydrogenase complex
While much of the catabolism of amino acids takes place in the
liver, the branched chain amino acids are oxidized as primary
fuels in muscle, adipose, kidney, and brain tissues.
CLINICAL CORRELATION:
maple syrup disease;
Defective branched-chain a-keto acid dehydrogenase complex;
urine has odor of maple syrup, mental and physical retardation
UNLESS patients are placed on a diet low in valine, isoleucine
and leucine early in life.
OXYGENASES ARE REQUIRED
FOR THE DEGRADATION OF
AROMATIC AMINO ACIDS
Monooxygenase- one atom of O2 appears
in the product and one in H20.
CLINICAL
CORRELATION:
MUTATIONS IN THE
GENE ENCODING
PHENYLALANINE
HYDROXYLASE CAUSE
PHENYLKETONURIA
More than 200 mutations have
been identified. Mutations
effecting the active site, the
biopterin binding site, and
other regions of the protein
are indicated as colored
spheres.
AROMATIC AMINO ACID
METABOLISM
Clinical Correlation:
Phenylketonuria-phenylalanine
accumulates in body fluids, if
untreated, severe mental
retardation. Treatment-low
phenylalanine diet.
Tyrosinemias-if untreated,
weakness, self-mutilation,
liver damage, mental
retardation. Treatment?
Alkaptonuriahomogentisate
accumulates in the
urine, and is
excreted, which
turns dark on
standing due to the
oxidation of
homogentisate.
Harmless.
TRYPTOPHAN DEGRADATION
Nearly all cleavages of aromatic rings in biological
systems are catalyzed by dioxygenases.
SUMMARY OF DEFECTS IN AMINO
ACID CATABOLISM THAT
CONTRIBUTE TO HUMAN DISEASE
FATES OF THE CARBON
SKELETONS OF THE AMINO ACIDS
SOURCES AND FATES
OF AMINO ACIDS IN THE BODY
AMINO ACID BIOSYNTHESIS
1.
The nitrogen in amino acids, purines, pyrimidines
and other biomolecules ultimately comes from
atmospheric N2.
2. This process begins with the reduction of N2 to NH3.
This process is called NITROGEN FIXATION, and is
carried out by some bacteria.
3. Since nitrogen fixation does not take place in higher
organisms, the source of nitrogen for amino acid
biosynthesis in humans are the metabolites of dietary
nitrogen.
AMINO ACIDS ARE MADE FROM
METABOLITES OF THE MAJOR
METABOLIC PATHWAYS
MOST MICROORGANISMS CAN SYNTHESIZE
ALL 20 AMINO ACIDS
HUMANS CAN ONLY SYNTHESIZE 11 AMINO ACIDS
The essential amino acids cannot be made
by humans and must be obtained in the diet.
1. The synthesis of many of the amino
acids is a simple reversal of their
degradation, utilizing a
transamination reaction.
2. Amino acids skeletons end up as
major metabolic intermediates
during degradation. Likewise, amino
acids are also biosynthesized from
major metabolic intermediates.
SOURCES AND FATES
OF AMINO ACIDS IN THE BODY
BIOSYNTHETIC FATES OF THE
AMINO ACIDS:
1. Protein synthesis (Dr. Lee)
2. Nucleic acid synthesis (Dr. Lee)
3. Heme synthesis (Dr. Luduena)
4. Thyroid hormone synthesis (Dr. Adamo)
5. Neurotransmitter synthesis
6. Spermine and spermidine
7. Creatine and phosphocreatine
Several amino acids can function as
neurotransmitters without any
chemical modification:
Glutamate
Glycine
Aspartate
MOST OF THE SMALL-MOLECULE
NEUROTRANSMITTERS ARE
AMINO ACIDS OR THEIR DERIVATIVES
*
Tyrosine
Tyrosine
Tyrosine
Glutamate
Tryptophan
Histidine
* (not directly from an amino acid, from acetyl CoA + choline)
CATHECHOLAMINE
BIOSYNTHESIS
GABA BIOSYNTHESIS
HISTAMINE BIOSYNTHESIS
SEROTONIN BIOSYNTHESIS
BIOSYNTHESIS OF
SPERMINE AND SPERMIDINE
BIOSYNTHESIS OF
CREATINE AND
PHOSPHOCREATINE
BIOSYNTHETIC FATES OF THE
AMINO ACIDS:
1. Protein synthesis
2. Nucleic acid synthesis
3. Heme synthesis
4. Thyroid hormone synthesis
5. Neurotransmitter synthesis
6. Spermine and spermidine
7. Creatine and phosphocreatine
SOURCES AND FATES
OF AMINO ACIDS IN THE BODY