All tissues have some capability for synthesis of the non-essential amino acids, amino acid remodeling, and conversion of non-amino acid carbon skeletons into amino acids and other derivatives that contain nitrogen.  However, the liver is the major site of nitrogen metabolism in the body. In times of dietary surplus, the potentially toxic nitrogen of amino acids is eliminated via transaminations, deamination, and urea formation.

1. Amino Acids Metabolism
Rajendra Dev Bhatt, PhD Scholar
Asst. Professor
Clinical Biochemistry & Laboratory Medicine
Dhulikhel Hospital-Kathmandu University Hospital
Fellow: Translational Research (2018-2022) in CVD in Nepal,
NIH, USA

2. All tissues have some capability for synthesis of
the non-essential amino acids, amino acid
remodeling, and conversion of non-amino acid
carbon skeletons into amino acids and other
derivatives that contain nitrogen.
However, the liver is the major site of nitrogen
metabolism in the body.
In times of dietary surplus, the potentially toxic
nitrogen of amino acids is eliminated via
transaminations, deamination, and urea
formation.

3. The carbon skeletons are generally conserved as
carbohydrate, via gluconeogenesis, or as fatty
acid via fatty acid synthesis pathways.
In this respect amino acids fall into three
categories: glucogenic, ketogenic, or glucogenic
and ketogenic.
All amino acids except lysine and leucine are at
least partly glucogenic. Lysine and leucine are the
only amino acids that are solely ketogenic, giving
rise only to acetyl-CoA or acetoacetyl-CoA,
neither of which can bring about net glucose
production.

4. A small group of amino acids comprised of
isoleucine, phenylalanine, threonine, tryptophan,
and tyrosine give rise to both glucose and fatty
acid precursors and are thus, characterized as
being glucogenic and ketogenic.
During times of starvation the reduced carbon
skeleton is used for energy production, with the
result that it is oxidized to CO2 and H2O.

5. Essential vs. Nonessential Amino Acids
Nonessential: Alanine, Asparagine, Aspartate,
Cysteine, Glutamate, Glutamine, Glycine, Proline,
Serine, Tyrosine
Essential: Arginine*, Histidine, Isoleucine,
Leucine, Lysine, Methionine*, Phenylalanine*,
Threonine, Tryptophan, Valine
*The amino acids arginine, methionine
and phenylalanine are considered semi-essential

7. Catabolism

8. Catabolism
Accounted for 10-15% of human energy
production
20 pathways converge to 6 major products:
7 aa are broken down to acetyl-CoA
5 aa to alpha-ketoglutarate
4 to succinyl-CoA
2 to fumarate
2 to oxaloacetate

9. Simple, Hydroxy and Sulfur Containing
Amino Acids: Glycine, Serine, Methionine, Cysteine
GLYCINE (GLY):It is the simplest, non-essential and
glucogenic amino acid, formed:
1. From serine: The beta carbon of serine is channeled
into the one carbon pool, carried by THFA (tetra
hydro folic acid). The alpha carbon of serine
becomes the alpha carbon of glycine

10. 2. From threonine: by the activity of
threonine aldolase

11. Metabolic Functions of Glycine
Glycine may be used for the biosynthesis of the
following compounds:
i. Creatine, creatine phosphate and creatinine
ii. Heme
iii. Purine nucleotides
iv. Glutathione
v. Conjugating agent
vi. Neurotransmitter

12. SERINE
Serine is an aliphatic hydroxy amino acid. It is
nonessential and glucogenic.

13. Catabolism of Serine

14. Metabolic Functions of Serine
• One-carbon group: Serine donates one-carbon
group to the one-carbon pool.
• Cysteine: Serine is used for the formation of cysteine
• Alanine: Serine is converted to alanine by
dehydration followed by transamination.
• Used for synthesis of phospholipids, such as
phosphatidyl serine
• Drugs: Serine analogues are used as drugs and they
inhibit nucleotide synthesis . Azaserine is an anti-
cancer drug and cycloserine is an antituberculous
drug.

15. Methionine
It is sulfur
containing, essential,
glucogenic amino
acid. Degradation of
methionine results in
the synthesis of
cysteine.

16. CYSTEINE
It is non-essential and
glucogenic. Cysteine is
present in large quantity
in keratin of hair and
nails. Formation of
Cysteine is by using the
carbon skeleton
contributed by serine
and sulfur originating
from methionine.

17. Metabolic Functions of Cysteine
• Formation of Glutathione: The role of glutathione in the
absorption of amino acid and Metabolic role of GSH is mainly in
reduction reactions.
• Glutathione is present in the RBCs. This is used for inactivation of
free radicals formed inside RBC.
• The met-Hb is unavailable for oxygen transport. Glutathione is
necessary for the reduction of methemoglobin (ferric state) to
normal Hb (ferrous state).
• Conjugation for Detoxification: Glutathione helps to detoxify
several compounds by transferring the cysteinyl group, e.g.
a. organo phosphorus compounds
b. halogenated compounds
c. nitrogenous substances (chloro dinitro benzene)
d. heavy metals
e. drug metabolism.

18. Cystinuria
• Cystinuria is one of the inborn errors of metabolism. It
is an autosomal recessive condition.
• HOMOCYSTINURIAS: Normal homocysteine level
in blood is 5-15 micromol/L. In diseases, it may be
increased to 50 to 100 times. Moderate increase is seen
in aged persons, vitamin B12 or B6 deficiency, tobacco
smokers, alcoholics and in hypothyroidism. Substantial
increase is noticed in congenital enzyme deficiencies. If
homocysteine level in blood is increased, there is
increased risk for coronary artery diseases.

19. Acidic, Basic and Branched Chain Amino
Acids (Glutamic Acid, Aspartic Acid, Lysine,
Arginine, Histidine, Valine, Leucine, Isoleucine)

20. GLUTAMIC ACID
Transamination
reactions: Most
amino acids transfer
their amino group to
alpha keto glutaric
acid to form glutamic
acid

21. • Glutamic acid is also formed during the
metabolism of histidine, proline and arginine
• Glutamic acid enters the TCA cycle, becomes
oxaloacetate and goes to glucogenic pathway.

22. GLUTAMINE
• It is a glucogenic amino acid. It is synthesized
from glutamic acid

23. ASPARTIC ACID
• Aspartate, on transamination gives rise to
oxaloacetate which initiates the TCA cycle.
Aspartate amino transferase (AST) transfers
the amino group of aspartate to alpha
ketoglutarate to form oxaloacetate.

24. ASPARAGINE
• Aspartate reacts with ammonia to form asparagine
• Asparagine can be hydrolyzed to aspartate and NH3 by
asparaginase.
• L-asparaginase is an anticancer drug against
leukemias and lymphomas, because those cells cannot
synthesize asparagine; the enzyme will destroy the
available asparagine in the blood; so the cancer cells
will die. Asparagine is a glucogenic amino acid.

25. LYSINE
• Lysine is an essential basic amino acid. It is
deficient in cereals. It does not undergo
transamination. Lysine is predominantly
ketogenic.
• Lysine is found in large quantities in histones,
the basic protein associated with nucleic acids.
• Lysine is the precursor of carnitine

26. ARGININE
• It is a highly basic, semi-essential amino acid.
Arginine is glucogenic.
• In the urea cycle, arginine splits into urea and
ornithine .

27. HISTIDINE
• Histidine has an
imidazole ring. It is
a semiessential
basic amino acid.
• Histidine residues
of albumin and
hemoglobin play a
significant role in
buffering action.

28. Histidinemia
• It is an autosomal recessive disease. The
deficiency of histidase leads to accumulation
of histidine in blood and body fluids and
increased excretion of imidazole pyruvic acid
in urine.
• The clinical features include mental
retardation and delayed speech development.
A low histidine diet may have some effect.

29. Leucine, Isoleucine, and Valine Catabolism:
Branched-Chain Amino Acids (BCAA)
• This group of essential amino acids is identified
as the branched-chain amino acids, BCAA
• The catabolism of all three amino acids occurs in
most cells but the highest rates of catabolism
takes place in skeletal muscle.
• The catabolism of all three of these amino acids
uses the same enzymes in the first two steps. The
first step in each case is a transamination using a
pyridoxal phosphate-dependent BCAA
aminotransferase (termed a branched-chain
aminotransferase, BCAT).

31. Aromatic Amino Acids
PHENYLALANINE:
• Phenylalanine is an essential,
aromatic amino acid. The need
for phenylalanine becomes
minimal, if adequate tyrosine is
supplied in the food.
• This is called the sparing
action of tyrosine on
phenylalanine. It is partly
glucogenic and partly
ketogenic.

32. TYROSINE
• Tyrosine is an aromatic amino acid. It is
synthesized from phenylalanine, and so is a
non-essential amino acid. The need for
phenylalanine becomes minimal, if adequate
tyrosine is supplied in the food. Tyrosine is
partly glucogenic and partly ketogenic.

33. Catabolism of
Tyrosine and
Phenylalanine

34. • Important Specialized Products from
Tyrosine:
1. Melanin
2. Catecholamines (Epinephrine)
3. Thyroxine

35. PHENYL KETONURIA (PKU)
• Deficiency of phenyl alanine hydroxylase is the
cause for this disease. The genetic mutation may
be such that either the enzyme is not synthesized,
or a non-functional enzyme is synthesized.
• There are 5 types of PKU described. Type I is the
classical one, described below. It is due to
phenylalanine hydroxylase deficiency. Types II
and III are due to deficiency of dihydrobiopterin
reductase. Type IV and V are due to the
deficiency of the enzyme synthesizing biopterin.

36. • Phenylalanine could not be
converted to tyrosine. So
phenylalanine accumulates.
Phenylalanine level in blood
is elevated.
• So alternate minor pathways
are opened Phenyl ketone
(phenyl pyruvate), phenyl
lactate and phenyl acetate are
excreted in urine.

37. ALKAPTONURIA
This is based on the observation that the urine
becomes black on standing when it becomes
alkaline. Sir Archibald Garrod in 1902 reported
that patients complain that their underwears are
getting blackened. Garrod concluded that the
disease is inherited and it is due to the deficiency
of the enzyme required for further metabolism of
homogentisic acid.

38. • Alkaptonuria is an autosomal recessive condition
with an incidence of 1 in 250,000 births.
• The metabolic defect is the deficiency of
homogentisate oxidase
• This results in excretion of homogentisic acid in
urine.
• It is compatible with fairly normal life.
• The only abnormality is the blackening of urine
on standing.

39. • The homogentisic acid is oxidized by polyphenol
oxidase to benzoquinone acetate It is then
polymerized to black colored alkaptone bodies.
• By the 3rd or 4th decade of life, patient may develop
ochronosis (deposition of alkaptone bodies in
intervertebral discs, cartilages of nose, pinna of ear).
Black pigments are deposited over the connective
tissues including joint cavities to produce arthritis.
• No specific treatment is required. But minimal protein
intake with phenylalanine less than 500 mg/day is
recommended.

40. Summary of tyrosine metabolism

41. TRYPTOPHAN
• Tryptophan is an amino acid needed for
normal growth in infants and for the
production and maintenance of the body's
proteins, muscles, enzymes, and
neurotransmitters.
• It is an essential amino acid. This means our
body cannot produce it, so you must get it
from our diet.

42. Substances produced from tryptophan:
1. Alanine (glucogenic)
2. Acetoacetyl CoA (ketogenic)
3. Formyl group (One-carbon unit)
4. Niacin and NAD+
5. Serotonin
6. Melatonin
7. Hydroxy indole acetic acid (excretory product)
8. Indican (excretory product)

44. Proline
• Proline is a non-essential glucogenic amino acid.
• Proline is made into glutamate, which enters the
citric acid cycle for complete oxidation.
• Proline dehydrogenase deficiency results in an
inborn error of metabolism named as type II
hyperprolinemia.
• Due to the deficiency of glutamate
semialdehyde dehydrogenase, type II
hyperprolinemia results.