Catabolism of amino acid

Catabolism of
amino acid


       At the end of this lecture, student will be able to

the catabolism of amino acid

      Explain Transamination

      Describe Deamination

      Describe Decarboxylation

ammonia toxicity

Amino acid pool

turnover is the balance between protein synthesis and protein degradation

        More synthesis than breakdown indicates an
anabolic state –positive nitrogen balance, more breakdown than synthesis
indicates a catabolic state negative nitrogen balance

Catabolism of amino acid

Ø  Amino
group of aminoacid – utilized for formation of urea – excretory end product of
protein metabolism

Ø  Carbon
skeleton of amino acid converted to keto acid which meet one of the following

for energy

for synthesis of glucose

of fat or ketone bodies

of non-essential aminoacids


Ø  Transfer
of amino group from amino acid to keto acid catalyzed by a group of enzymes
transaminases or aminotransferases to form a new amino acid and keto acid – transamination

Ø  For
this process pair of amino acids and a pair of keto acids are involved

Ø  It
involves interconversion of a pair of amino acids and a pair of keto acids

Salient features of Transamination

transaminases requires pyridoxal phosphate (PLP) co-enzyme, which is obtained
from vit-B6

       Specific transaminases exist for
each pair of amino and keto acids

free NH3 liberated, only transfer of amino group occurs

is a reversible process

for production of Non-essential amino acids

in energy generation

amino acids except lysine, threonine, proline and hydroxy proline participate
in transamination

Mechanism of Transamination

occurs in two steps

  1. Transfer
    of amino group to coenzyme pyridoxal phosphate to form pyridoxamine

2.       The
amino group of pyridoxamine phosphate is then transfer to a keto acid to
produce new amino acid and enzyme with PLP is regenerated

       Glutamate + oxaloacetate   ———– >           α-ketoglutarate + aspartate

pyridoxal phosphate


removal of amino group from amino acid as NH3Deamination

of ammonia for urea cycle

is classified in to two types

Oxidative deamination

                2. Non
oxidative deamination

Transamination and deamination occurs simultaneously,
involving glutamate as central molecule

Oxidative Deamination

       Liberation of free ammonia from the
amino group of amino acids coupled with oxidation

       Takes place mostly in liver and

       Purpose of oxidative deamination is
to provide NH3 for urea synthesis and
α-keto acids for a variety of reactions, including energy generation

Role of
Glutamate Dehydrogenase (GDH):

       In the process of transamination,
the amino groups of most amino acids are transferred to a-ketoglutarate to
produce glutamate

       Thus, glutamate serves as a
collection centre for amino groups in the biological system

       Glutamate rapidly undergoes
oxidative deamination, catalysed by
GDH to liberate ammonia

       Enzyme is unique and utilize either
NAD+ or NADP+ as a co-enzyme

       Conversion of glutamate to
α-ketoglutarate occurs through the formation of an intermediate,

       GDH is involved in both catabolic
and anabolic reactions

of GDH activity:

       GDH is a zinc containing
mitochondrial enzyme

       GDH is controlled by allosteric

       GTP and ATP inhibit GDH

       GDP and ADP activate GDH

       Steroid and thyroid hormones inhibit

       After ingestion of a protein rich
meal, liver glutamate level is elevated

Oxidative deamination by amino acid oxidase

       L-Amino acid oxidase and D-amino
oxidase are
flavoproteins, possessing FMN and FAD, respectively

       Act on corresponding amino acids( L
or D) to produce
α-keto acids and NH3

       In this reaction, oxygen is reduced
to H2O2, which is later decomposed by catalase

       Activity of L-amino acid oxidase is
much low while that of D-amino acid oxidase is high in tissues(mostly liver and

       L –Amino acid oxidase does not act
on glycine and dicarboxylic acids

       This enzyme, due to its very low
activity, does not appear to play any significant role in the amino acid

Non oxidative deamination

       Some of the amino acids can be
deaminated to liberate NH3 without undergoing oxidation

a. Amino
acid dehydrases:

       Serine, threonine and homoserine are
the hydroxy amino acids

       They undergo non-oxidative
deamination, catalysed by PLP-dependent dehydrases (dehydratase)

b. Amino
acid desulfhydrases:

       The sulfur amino acids, namely
cysteine and homocysteine undergo deamination coupled with desulfhydrationto
give keto acids

c. Deamination of histidine :

       The enzyme histidase acts on histidine to liberate NH3
by a
deamination process


       Tissues like liver and
microorganisms of the intestinal tract contain enzymes called decarboxylases
which require pyridoxal phosphate as coenzyme

       They remove CO2 from
carboxylic group and convert aminoacid to its corresponding amine

       The physiologically active amines
epinephrine, nor-epinephrine, dopamine, serotonin,
α-amino butyrate and histamine are formed through decarboxylation of the
corresponding precursor amino acids

Function of ammonia

       Ammonia is not just a waste product
of nitrogen metabolism. lt is involved (directly or via glutamine) for the
synthesis of many compounds in the body. These include nonessential amino
acids, purines, pyrimidines, amino sugars, asparagine etc

        Ammonium ions (NHa*) are very important to
maintain acid-base balance of the body

Disposal of ammonia

       The organisms, during the course of
evolution, have developed different mechanisms for the disposal of ammonia from
the body. The animals in this regard are of three different types

a. Ammoniotelic: The aquatic animals dispose of NH3
into the    surrounding water

b. Uricotelic: Ammonia is converted mostly to uric acid e.g.
reptiles and birds.

c. Ureotelic: The mammals including man convert NH3
to urea. Urea is a non-toxic and soluble compound, hence easily excreted

Toxicity of ammonia

       Even a marginal elevation in the
blood ammonia concentration is harmful to the brain

traces 10-20 mg/dl is present in blood

       When accumulates in the body,
results in slurring of speech and blurring of the vision and causes tremors

       lt may lead to coma and finally
death, if not corrected

       Hyperammonemia : Elevation in blood NH3

       lmpairment in urea synthesis due to a defect in
any one of the five enzymes is described in urea synthesis

       Hyperammonemia leads to mental

       Acquired hyperammonemia may be due
to hepatitis, alcoholism etc.


turnover is the balance between protein synthesis and protein degradation

of amino group from amino acid to keto acid is known as transamination

of amino group from amino acid as NH3 is known as deamination

transamination required PLP co-enzyme

elevation in blood ammonia concentration is harmful to the brain

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