Degradation of Amino Acids
What are amino acids?
Proteins are polymers of amino acids, with each amino acid residue joined to
its neighbor by a specific type of covalent bond.
(The term residue reflects the loss of the elements of water when one
amino acid is joined to another.)
General Structure of Amino Acid
This structure is common to all (except Proline, a cyclic amino acid). The R
group or side chain (blue) attached to the carbon (green) is different in each
• Asparagine was the first discovered amino
acid in 1806.
• The last discovered was threonine in 1938.
Structural Classification of Amino Acids
1. With aliphatic side chains (Gly, Ala, Val, Leu, Ile)
2. With side chain containing –OH group (Ser, Thr)
3. With side chain containing S atom (Cys, Met)
4. With side chain containing acid groups (Asp, Asn, Glu, Gln)
5. Basic amino acids (His, Lys, Arg)
6. Side chain having aromatic ring (Phe, Tyr, Trp)
7. Secondary amino acid (Pro)
The amino acid residues in protein molecules are exclusively L stereoisomers.
D-Amino acid residues have been found only in a few, generally small
peptides, including some peptides of bacterial cell walls and certain peptide
During degradation amino acids lose their NH2
group to form �-keto acids, the c-skeleton of
�-keto acids on oxidation gives-
• 3-C / 4-C unit compound Gluconeogenesis
Metabolic Fate of Amino Acid
Amino acid from
Urea Uric Acid
Releases ammonia as excretory product.
e.g., aquatic vertebrates, bony fishes and larvae
Releases urea as excretory product.
e.g., Terrestial vertebrates
Releases uric acid as excretory product.
e.g., birds, reptiles
Most common amino acids can be converted into
the corresponding keto acid by transamination.
Pyridoxal Phosphate (PLP) and Aminotransferases
PLP participate in the transfer of �-amino group to �-ketoglutarate leaving behind
� -keto acid analog of amino acid in the presence of enzymes
(transaminase/aminotransferases having prosthetic group-pyridoxal phosphate
Pyridoxal phosphate functions as an intermediate carrier of amino groups at the active
site of aminotransferases.
It undergoes reversible
1- aldehyde form
-which can accept an amino
2- aminated form
-which can donate its amino
group to an -keto acid
Reactions at the �- carbon include-
• racemizations (interconverting L- and D-amino acids)
Role of Pyridoxal phosphate:
As bond to the �- carbon of the substrate is broken, removing either a proton or a carboxyl
group. The electron pair left behind on the � -carbon would form a highly unstable carbanion.
Then, pyridoxal phosphate provides resonance stabilization of this intermediate. The highly
conjugated structure of PLP (an electron sink) permits delocalization of the negative charge.
Glutamate Releases Its Amino Group
as Ammonia in the Liver
Amino groups from many of the amino acids are
collected in the liver in the form of the amino
group of L-glutamate molecules.
amino group must be removed
Glutamate transported from the cytosol into mitochondria
In mitochondria oxidative deamination catalyzed by L-glutamate
Classification of amino acid on the basis of their
Glucogenic amino acids are those that give rise to a net
production of pyruvate or TCA cycle intermediates,
such as α-ketoglutarate or oxaloacetate, all of which
are precursors to glucose via gluconeogenesis.
Ketogenic are those which degrades to give
acetoacetate or acetyl CoA.
e.g., Leucine & lysine
• Both glucogenic & ketogenic
e.g., Phenylalanine, Tyrosine, Tyrptophan, Isoleucine
• In ureotelic organisms, the ammonia
deposited in the mitochondria of hepatocytes
is converted to urea in the urea cycle.
• This pathway was discovered in 1932 by
Hans Krebs and Kurt Henseleit.
• Urea production occurs almost exclusively in
• The first amino group to enter the urea cycle is derived from
ammonia in the mitochondrial matrix—NH4
• The NH4 generated in liver mitochondria is immediately used,
together with CO2 (as HCO3 ) produced by mitochondrial
respiration, to form carbamoyl phosphate in the matrix .
• This ATP-dependent reaction is catalyzed by carbamoyl phosphate
• The carbamoyl phosphate functions as an activated carbamoyl group
donor enters the urea cycle.
• Carbamoyl phosphate donates its carbamoyl group to ornithine to
form citrulline, with the release of Pi. The reaction is catalyzed by
Citrulline passes from the mitochondrion to the cytosol.
Second amino group now enters from aspartate (generated in mitochondria by
transamination and transported into the cytosol) by a condensation reaction
between the amino group of aspartate and the ureido(carbonyl) group of
citrulline, forming argininosuccinate, catalyzed by argininosuccinate synthetase,
• Argininosuccinate is then cleaved by argininosuccinase to form free
arginine and fumarate
• fumarate enters mitochondria to join the pool of citric acid cycle
• Arginase cleaves arginine to yield urea and ornithine.
• Ornithine is transported into the mitochondrion to
initiate another round of the urea cycle.
• catalysed by glutamate dehydrogenase
Glutamine glutaminase Glutamate + NH3
OOC Proline oxidase N
Pyrroline 5 carboxylate
How Propionyl CoA converting to Succinyl CoA
I step enzyme- Propionyl CoA carboxylase
II step enzyme- Mutase
alpha KGA Glu
alpha-keta isovaleric acid
isobutaryl CoA DH
enoyl CoA hydratase
Beta hydroxy butyric acid
Methyl Malonic acid semialdehyde
Amino Acids Degrading to Acetyl CoA &
Catalysed by alanine amino transferase
Serine dehyratase also requires a pyridoxal phosphate
β-elimination of the hydroxyl group of serine to form an
amino acrylate intermediate which tautomerizes into the
imine which is then hydrolyzed to produce ammonia and
• Principles of Biochemistry, Lehninger
• Concise Textbook of Chemistry, G.Rajagopal
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