BIC 101 :: Lecture 28 :: TRANSAMINATION, DEAMINATION AND DECARBOXYLATION

  • Protein metabolism is a key physiological process in all forms of life. 
  • Proteins are converted to amino acids and then catabolised. 
  • The complete hydrolysis of a polypeptide requires mixture of peptidases because individual peptidases do not cleave all peptide bonds.
  •  Both exopeptidases and endopeptidases are required for complete conversion of protein to amino acids.

Amino acid metabolism         

  • The amino acids not only function as energy  metabolites but also used as  precursors of many physiologically important  compounds such as heme, bioactive amines, small  peptides,  nucleotides and nucleotide coenzymes.
  •  In normal human beings about 90% of the energy  requirement is met by oxidation of carbohydrates and fats.  The  remaining 10% comes from oxidation of the carbon skeleton of  amino acids. 
  • Since the 20 common protein amino acids are  distinctive in terms of their carbon skeletons, amino acids  require unique degradative pathway.
  •  The degradation of  the carbon skeletons of 20 amino acids converges to just seven  metabolic intermediates namely.

i.  Pyruvate
ii.  Acetyl CoA
iii.  Acetoacetyl CoA
iv.  ‑Ketoglutarate
v.  Succinyl CoA
vi.  Fumarate
vii.  Oxaloacetate

  • Pyruvate,  ‑ketoglutarate,  succinyl CoA,  fumarate and  oxaloacetate can serve as precursors for glucose synthesis  through gluconeogenesis.Amino acids giving rise to these  intermediates are termed as glucogenic. 
  • Those amino acids  degraded to yield acetyl CoA or acetoacetate are termed ketogenic  since these  compounds are used to synthesize  ketone bodies.  
  • Some amino acids  are both glucogenic and ketogenic (For example,  phenylalanine, tyrosine, tryptophan and threonine.

Catabolism  of amino acids
The important reaction commonly employed in the  breakdown of an amino acid is always the removal of its  ‑amino group.  The product ammonia is excreted after conversion  to urea or other products and the carbon skeleton is degraded to  CO2 releasing energy.  The important reaction involved in the  deamination of amino acids is
i.  Transamination
ii.  Oxidative deamination
iii.  Non oxidative deamination
Transamination

  • Most amino acids are deaminated by transamination  reaction catalysed by aminotransferases or transaminases.
  • The ‑amino group present in an amino acid is transferred to an  ‑keto acid to yield  a new amino acid and the  ‑keto acid of the original amino acid.
  •  The predominant amino group acceptor is ‑keto glutarate.  Glutamate's amino group is then transferred to oxaloacetate in a second transamination reaction yielding  aspartate.

Glutamate + oxaloacetate     ----------          -ketoglutarate + aspartate
                                                    pyridoxal phosphate

  • Pyridoxal phosphate, the coenzyme of pyridoxine  (vitamin B6) plays an important role in these reactions.
  • Amino  transferase  reactions  occur in two stages.
    • Pyridoxal phosphate is covalently attached to the amino  transferases via a Schiff's base linkage formed between the  aldehyde group of pyridoxal phosphate and the epsilon amino group  of lysine residue of the enzyme.  Pyridoxal phosphate  is converted to pyridoxamine phosphate.
    •  In the second stage, the  amino group attached to pyridoxamine phosphate is transferred to  a different keto acid to yield a new amino acid and  releases pyridoxal  phosphate 

Oxidative deamination

  • Transamination  does not result in net deamination,  since one amino acid is replaced by another amino acid.
  • The function of transamination is to funnel the amino nitrogen into one or a few amino acids. 
  • For glutamate to play a role in the net conversion of amino groups to ammonia, a mechanism for  glutamate deamination is needed so that  -ketoglutarate can be regenerated for further transamination.
  • The generation is accomplished by the oxidative deamination of glutamate by glutamate dehydrogenase. 
  • Glutamate is oxidatively deaminated in the mitochondrion by  glutamate dehydrogenase.   NAD+ or  NADP+  functions  as the coenzyme. 
  • Oxidation  is thought to occur with the transfer of a hydride ion from glutamate's carbon to NAD(P)+ to form  ‑iminoglutarate, which is then hydrolysed to ‑ketoglutarate  and ammonia. 
  • The ammonia produced is then converted to urea in  mammals

      Two non-specific amino acid oxidases namely, L‑amino acid  and D‑amino acid oxidases catalyse the oxidation of L and  D‑amino acids utilizing FAD as their coenzymes.


Amino acid + FAD + H2O  ------------    -Keto acid + NH3 + FADH2

Non-oxidative deamination

  • Amino acids such as serine and histidine are deaminated  non-oxidatively

 The other reactions involved in the  catabolism of amino  acids are decarboxylation, transulfuration, desulfuration,  dehydration etc.

Decarboxylation

  • The decarboxylation process is important since  the products of decarboxylation reactions give rise to  physiologically active amines.
  • The enzymes,  amino acid  decarboxylases are pyridoxal  phosphate‑ dependent enzymes. 
  • Pyridoxal phosphate forms  a  Schiff's base with the amino acid so as to stabilise the  ‑carbanion   formed  by  the cleavage of   bond  between carboxyl and -carbon atom. 
  • The physiologically active amines epinephrine, nor-epinephrine, dopamine, serotonin, ‑amino butyrate and histamine are formed through   decarboxylation  of  the  corresponding precursor amino acids.
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