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.
ii. Acetyl CoA
iii. Acetoacetyl CoA
v. Succinyl CoA
- 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
ii. Oxidative deamination
iii. Non oxidative deamination
- 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, 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
- 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
- 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.
- 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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