Synthesis of non-essential

amino acid

Ms M. Mombeshora
HBC 202 Lecture 02
Sources of N and C in amino acids
• Amino acids are classically considered as the
building blocks from which proteins are
synthesised
• Additionally, some play a major role in
– the regulation of protein turnover and signal
transduction
– transport of nitrogen and carbon across the
organs
– neurotransmission
Sources of N and C in amino acids
• The biosynthesis of amino acids involves
several biochemical pathways in which amino
acids are assembled from other precursors
• The biosynthesis of amino acids is distinct
from that involving lipids or carbohydrates
because it includes the use of nitrogen
• The fixation of nitrogen is a process that
converts atmospheric nitrogen to a form that
can be used biologically
Sources of N and C in amino acids
• The pathways for the synthesis of
essential amino acids are present only in
microorganisms and plants
• Nine of 12 nonessential amino acids are
synthesised from amphibolic
intermediates
• Whereas the amino acids tyrosine and
cysteine derive from essential amino acids
 Important enzymes
Important enzymes in the synthesis of
nonessential amino acids
Amino acid transaminases
glutamate dehydrogenase
glutamine synthetase
Sources of N and C in amino acids
• Major pathway by which ammonia is incorporated
into amino acids is through the reductive
amination of α‐ketoglutarate to glutamate
• Ammonia is highly toxic for animals
• Glutamine is a nontoxic carrier of ammonia
• In the human adult as much as 200–250 g of
proteins are degraded daily, and their constituent
amino acids are in large part reutilised in protein
synthesis
Sources of N and C in amino acids

• Amino acid deficiency states can result if any of

the essential amino acid is present in inadequate
amounts or omitted from the diet
• Alanine, glutamate and glutamine are crucial links
between energy and protein metabolism
• Moreover, glutamine and alanine biosynthesis in
the peripheral tissues (muscle) provides a means
for the transport of carbon to the liver for
gluconeogenesis and nitrogen for ureagenesis
Sources of N and C in amino acids
• Amino acids may be derived by synthesis from
simple substances de novo synthesis, i.e., from
– glucose as a carbon source
– ammonium ion as a nitrogen source
– by their absorption from the diet
 Amino acids in human nutrition
• Every living cell must have a supply of amino
acids
• Constantly available for diverse synthetic
processes especially protein synthesis
• Alternatively oxidised to urea and carbon
dioxide as a source of energy
• The oxidation pathway starts with the transfer
of an amino group by a transaminase
 Amino acids in human nutrition
• The amino group is then fed into the urea
cycle
• The keto acid enters the citric acid cycle
• Glucogenic amino acids can be converted into
glucose via gluconeogenesis
 Synthesis of amino acids
• Plants and bacteria produce all of their amino
acids using NH4+ or NO3-

• Humans can synthesise 9 of the 20 amino

acids found in their proteins

• Nonessential amino acids are synthesised in

the body, while essential amino acids must be
obtained from diet
Pathways for amino acid synthesis
A variety of pathways are involved in the
synthesis of nonessential amino acids
• The body synthesises nonessential amino
acids
• The α-keto acid carbon skeletons are obtained
from the citric acid cycle or glycolysis and
converted to amino acids by transamination
 Amino acid synthesis
Nonessential amino acids are synthesized from
intermediates of glycolysis and the citric acid
cycle
 Nitrogen metabolism
• Amino acids are
synthesised from
intermediates of
glycolysis and citric acid
cycle
• Non essential amino
acids can be
synthesised
• Essential amino acids
must be obtained from
food
 Amino acid biosynthesis
Essential amino acids
• Unable to synthesise them
• Sources are plants and microbes
Nonessential amino acids
• Amine groups comes from Glu and Gln
• Some synthesised from essential amino acids
 Tyrosine from Phenylalanine
 Cysteine depends on sulphur from Methionine
Essential and nonessential amino acids
Essential amino acids Nonessential amino acids
Histidine Alanine
Isoleucine Arginine
Leucine Asparagine
Lysine Aspartate
Methionine Cysteine
Phenylalanine Glutamate
Threonine Glutamine
Tryptophan Glycine
Valine Proline
Serine
Tyrosine
 Nonessential amino acids
NOTE:
• Cys gets its sulphur atom
from met

• Tyr is hydroxylated phe

• SO IT’S NOT REALLY

NONESSENTIAL
 Conditionally essential amino acids
Note:
• Arg is essential in infants and children
• Most synthesised arg ornithine and via the
urea cycle
Arginine
Proline
Cysteine
Glycine
 Conditionally essential amino acids
• Conditionally” essential imply that there are
measurable limitations to the rate at which they
can be synthesised
• When this limit is attained, the amino acid in
question becomes an essential component of the
diet
• Although nitrogen of the amino acids mammals
can synthesise derives ultimately from either
glutamate or serine, some amino acids are
synthesised by more complex pathways than the
simple transamination of a keto acid
 Conditionally essential amino acids
Limitations can result from:
i. Ability to synthesis these amino acids
requires the provision of another amino acid,
as the C donor or as a donor of an accessory
group e.g S group of cysteine
 Conditionally essential amino acids
Limitation can result from
ii. some amino acids may be synthesized in
only a limited number of tissues
e.g the synthesis of both proline and arginine
is crucially dependent on intestinal
metabolism
 Conditionally essential amino acids
Limitations can result from:
iii. stressful circumstances, under which the
metabolic demands for the amino acids rise
to values that are beyond the biosynthetic
capacity of the organism. Such appears to be
the
proline nutrition of burned individuals
low-birth-weight infants, it is possible that
limitation by a frank lack of enzymatic activity
 Amino acid biosynthesis
• All are synthesized from common metabolic
intermediates
Non-essential
• Transamination of α-ketoacids that are available as
common intermediates
Essential
• Their α-ketoacids are not common intermediates
(enzymes needed to form them are lacking)
• So transamination isn’t an option
• But they are present in common pathways of micro-
organisms and plants
 Amino acid biosynthesis overview
(use of common intermediates)
GLUCOSE  GLUC-6-PHOSPHATE    RIB-5-PHOS→ HIS


3-PHOSPHOGLYCERATE  SERINE
 
 GLYCINE
E-4-PHOS + PEP CYSTEINE
 
PHE→TYR PYRUVATE  ALA
TRP  VAL
CITRATE LEU,
ILE
↓
OXALOACETATE, -KETOGLUTARATE
ASP, ASN, GLU, GLN, PRO, ARG, LYS, THR, MET
Synthesis of nonessential amino acids
• All (except tyr) synthesized from common
intermediates synthesized in cell

• Pyruvate
• Oxaloacetate
• α-Ketoglutarate
• 3-phosphoglycerate
Glucogenic and ketogenic amino acids
Overview of amino acid biosynthesis
Amino acid precursors are intermediates
in glycolysis the TCA and pentose phosphate

citrate
 Amino acid biosynthesis
• How are nonessential amino acids
synthesised?
• Are some amino acids used to build others?
Synthesis of nonessential amino acids
Consider:
• Pyruvate alanine
• Oxaloacetate aspartate
Synthesis of glutamate and glutamine
• α-ketoglutarate glutamate
• glutamate glutamine
 Synthesis of asparagine
• Aspartate Asparagine
• Catalysed by synthetase (cost ATP)
 Synthesis of arginine and proline
• Glutamate arginine
• Glutamate proline
Longer pathways
 Synthesis of serine
• 3-Phosphoglycerate serine
 Synthesis of glycine
• Serine glycine
 Synthesis of glycine
Enzyme that catalyse synthesis of glycine from
serine