Catabolism of amino acid

Catabolism of
amino acid

Objective

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

–      Explain
the catabolism of amino acid

–      Explain Transamination

–      Describe Deamination

–      Describe Decarboxylation

–      Explain
ammonia toxicity

Amino acid pool

•       Protein
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

•       Utilized
for energy

•       Used
for synthesis of glucose

•       Formation
of fat or ketone bodies

•       Production
of non-essential aminoacids

Transamination

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

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

•       Specific transaminases exist for
each pair of amino and keto acids

•       No
free NH₃ liberated, only transfer of amino group occurs

•       It
is a reversible process

•       Important
for production of Non-essential amino acids

•       Helps
in energy generation

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

Mechanism of Transamination

•       It
occurs in two steps

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

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

Deamination

•       The
removal of amino group from amino acid as NH₃ – Deamination

•       Liberation
of ammonia for urea cycle

•       It
is classified in to two types

                1.
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
kidney

•       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, α-iminoglutarate

•       GDH is involved in both catabolic
and anabolic reactions

Regulation
of GDH activity:

•       GDH is a zinc containing
mitochondrial enzyme

•       GDH is controlled by allosteric
regulation

•       GTP and ATP inhibit GDH

•       GDP and ADP activate GDH

•       Steroid and thyroid hormones inhibit
GDH

•       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
acid 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
kidney).

•       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
metabolism

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 non-oxidative
deamination process

Decarboxylation

•       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

•       Only
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
level

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

•       Hyperammonemia leads to mental
retardation.

•       Acquired hyperammonemia may be due
to hepatitis, alcoholism etc.

Summary

•       Protein
turnover is the balance between protein synthesis and protein degradation

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

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

•       All
transamination required PLP co-enzyme

•       Marginal
elevation in blood ammonia concentration is harmful to the brain