Amino acid metabolism

Applied Biochemistry
Class B.Pharm IV Semester
15-03-2013

Aims of amino acid metabolism

1.How does the body handle the digestion and
absorption of 20 different amino acids?
2.How does the body control serum amino acid levels
and why?
3.How does the body safely dispose of nitrogen?
4.How do amino acids contribute to the glucose pool?

Introduction
AA contain nitrogen moiety which is not completely
oxidized in body .Generally, amino group is transferred
to keto acid to synthesize nonessential AA or
is removed or coverted to urea
Catabolic pathway of aminoacids involves
1)Removal of amino group: Oxidative deamination,
transamination, transdeamination
2)Metabolism of ammonia: Detoxification of ammonia
3)Metabolism of carbon skeleton

Sources and Uses of Amino Acids

Protein synthesis
Proteins in the diet
provide both essential
Nitrogen and carbon source
and non-essential
of general and special
amino acids
product biosynthesis
Turnover of
Energy source: glucogenic
endogenous proteins
(those that can be used for
the synthesis of glucose) or
De novo
Ketogenic (those whose
biosynthesis(nonmetabolism leads to ketone
essential amino acids)
bodies

Transamination
Transamination (or aminotransfer) is the reaction
between an amino acid and an alpha-keto acid. The
alfa- NH2 is transferred to a keto group .
This results in the amino acid being converted to the
corresponding -keto acid, while the reactant -keto
acid is converted to the corresponding amino acid
Transamination is accomplished by enzymes called
transaminases aminotransferases. Transamination
reactions are fully reversible
Transamination takes place principally in
liver,kidney ,heart, brain , but to small extent
transamination can take place in all tissues

Transamination
Transamination is the process by which human body
synthesizes non-essential amino acids .
Nearly all amino acids (except lysine, threonine,
proline and hydroxyproline) can be metabolized
with the loss of the -amino group to give the
corresponding -ketoacid.
The immediate acceptor for this amino group is the
cofactor, pyridoxal phosphate. Ultimately the amino
group is transferred to -ketoglutarate or pyruvate
to give the amino acids glutamate and alanine.

Transamination
This reaction is considered to be a
kinetically perfect reaction.depend on the availability
of alpha-keto acids.
The products usually are either alanine, aspartate or
glutamate, since their corresponding alpha-keto acids
are produced through metabolism of fuels.
All amino acids undergoing transamination can have
their amino group transferred to form glutamate.
NH3 formation does not take place in transamination
reaction. The process represents only an intermolecular transfer of NH2 groups without splitting
out of N as NH3.

Transamination

Importance of Trans-aminases
The liver, has a variety of transaminases to synthesize
and break down amino acids and to interconvert
energy storage molecules.
The concentrations of these in the serum are normally
low. However, if the liver is damaged, the becomes
more permeable and some of the enzymes leak out
into the blood stream
Measuring the concentrations of various
transaminases in the blood is important in the
diagnosing and tracking many diseases such as cells
in heart during a myocardial infarction.

Importance of Trans-aminases
These enzymes are released into from the cells and
lead to increases in their levels in the blood.
Measurement of these used to be part of diagnosing
heart attacks.
Very high elevations of the transaminases suggests
severe liver damage, such as viral hepatitis, liver
injury from lack of blood flow, or injury from drugs or
toxins.

Transaminases of clinical importance

Aspartate transaminase (Aspartate amino
transferase) previously known as SERUM
GLUTAMATE OXALOACETATE TRANSAMINASE
:SGOT It also is sometimes called AST
Aspartate + alfa oxaloglutarate OAA(Oxaloacetate) +
Glutamate

Transaminases of clinical importance

Alanine Transaminase (Alanine aminotransferase)
previously known as SERUM GLUTAMATE PYRUVATE
TRANSAMINASE :SGPT It also is sometimes called
ALT
Alanine + alfa oxoglutarate Pyruvic acid + Glutamate

Deamination
Deamination is the removal of an amine group from
a molecule. It is the process by which amino acids are
broken down.
In the human body, deamination takes place in the
liver. The amino group is removed from the amino
acid and converted to ammonia.
The rest of the amino acid is made up of mostly
carbon and hydrogen, and is recycled or oxidized for
energy.

Ammonia is toxic to the human system, and enzymes

convert it to urea or uric acid by addition of carbon
dioxide molecules in the urea cycle.

Deamination
Deamination is the process by which nitrogen of
amino acid is removed as NH3.There are two types of
deamination Oxidative deamination and Non oxidative
deamination
Oxidative deamination: In order to regenerate the
amino acceptor, -ketoglutarate, and to provide
ammonia for re-utilization or disposal it is necessary
to deaminate glutamate.
This is accomplished by the action of the enzyme
glutamate dehydrogenase (GDH) which is located in
the mitochondrial matrix.

Deamination
This reversible reaction utilizes both NAD+and NADP+.
Generally NAD+ is used in the oxidative deamination reaction
Coupling of this reaction with a transamination results in the
oxidative degradation of an amino acid to its corresponding
-ketoacid, the generation of ammonia and trapping energy
in the form of reduced pyridine nucleotide (NADH).

Deamination
The NADH can be re-oxidized in mitochondria by the
electron transport system; the carbon skeleton of the
amino acid (e.g.pyruvate) may enter into familiar
metabolic pathways and the ammonia will be reutilized or disposed of by the urea cycle.
Operating in the opposite direction NADPH is used in
the reductive amination direction with the
assimilation of ammonia and the formation of
glutamate
Sites of oxidative deamination is Liver and
kidney.L amino acid oxidase acts specifically on Laminoacids and oxidatively deaminate to form NH3 .
L amino acid oxidases are auto oxidizable flavo
proteins.

Non oxidative Deamination

The mammalian cells carry out non-oxidative
deamination reactions with the enzymes glutaminase ,
asparginase and histidinase, all of which yield ammonia
as a product. Glutaminase is probably one of the most
prominent. The action of glutaminase in the liver yields
glutamicacid and ammonia, the latter of which is
consumed by the urea cycle.
Amino acids like hydroxy AA,Histidine, Sulfur containing
AA, can be deaminated non oxidatively by specific
enzymes to form ammonia. They also do not fulfill major
role in ammonia formation

Non oxidative Deamination

Decarboxylation
Decarboxylation is the reaction by which CO2 is
removed from the COOH group of an amino acid,
resulting in formation of a biogenic amine.The
reaction is catalyzed by the enzyme decarboxylase
which requires pyridoxal phosphate as co
enzyme.Biogenic amines are derived from amino
acids by decarboxylation
Hisatamine from
histidine:Vasodialator(B.P-),HCL+, Pepsin+,
Liberated in anaphylatic reaction.

Taurine derived Cysteic acid derived from

cysteine. :constituent of bile acid.

Decarboxylation
Tryptamine from tryptophan :Tissue hormone,a
derivative of 5-OH tryptamine(serotonin),
Vasoconstriction and increase in B.P.
Ethanolamine derived from Serine :Forms
Choline,constituent of phospholipid like
cephalin.Decarboxylation of acetoacetate to
acetone occurs spontaneously without enzyme.
GABA:Gama amino butyric acid derived from
glutamic acid :Presynaptic inhibitor in brain,forms a
bypass in TCA cycle(GABA shunt)GABA shunt
:GABA by its conversion to succinic acid can form a
bypass in TCA cycle.Glutamate undergoes
decarboxylation to GABA ,which upon deamination will
form succinic semialdehyde

Thanks for your attention!