Amino acids are degraded through transamination and oxidation reactions. During degradation, amino acids lose their amino group to form alpha-keto acids. The carbon skeletons are then further oxidized, producing metabolites like pyruvic acid, acetoacetic acid, succinyl-CoA, oxaloacetic acid, or alpha-ketoglutaric acid. These intermediates can be converted to glucose, ketone bodies, or fed into the citric acid cycle. In ureotelic organisms, ammonia produced from amino acid degradation is incorporated into the urea cycle in the liver and converted to urea for excretion. Key enzymes and cofactors involved include transaminases, glutamate dehydrogenase

1. Degradation of Amino Acids
Presented By:
Anuradha Verma

2. 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
amino acid.
C
COO-
+
H3N H
R

3. • Asparagine was the first discovered amino
acid in 1806.
• The last discovered was threonine in 1938.

4. 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
antibiotics.
L-Alanine D-Alanine
C
COO-
+
H3N H
CH3
C
COO-
H NH3
+
CH3

6. Degradation of Amino
Acids

7. During degradation amino acids lose their NH2
group to form �-keto acids, the c-skeleton of
amino acids.
�-keto acids on oxidation gives-
• CO2
• H2O
• 3-C / 4-C unit compound Gluconeogenesis
Glucose

8. Metabolic Fate of Amino Acid
Amino acid from
ingested protein
Cellular Protein
Amino acid
Alpha keto
acid
Alpha keto
glutarate
glutamate
NH4
+
Glutamine
NH4
+
Urea Uric Acid
Liver

9. • Ammonotelic:
Releases ammonia as excretory product.
e.g., aquatic vertebrates, bony fishes and larvae
of amphibia.
• Ureotelic:
Releases urea as excretory product.
e.g., Terrestial vertebrates
• Uricotelic:
Releases uric acid as excretory product.
e.g., birds, reptiles

10. Transamination reaction
Most common amino acids can be converted into
the corresponding keto acid by transamination.

11. 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
(PLP) )
Pyridoxal phosphate functions as an intermediate carrier of amino groups at the active
site of aminotransferases.

12. It undergoes reversible
transformations between
1- aldehyde form
(pyridoxal phosphate)
-which can accept an amino
group and
2- aminated form
(pyridoxamine phosphate)
-which can donate its amino
group to an -keto acid

13. Reactions at the �- carbon include-
• racemizations (interconverting L- and D-amino acids)
• Decarboxylations
• transaminations
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.

14. 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
dehydrogenase

15. Classification of amino acid on the basis of their
end products
• Glucogenic
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
Ketogenic are those which degrades to give
acetoacetate or acetyl CoA.
e.g., Leucine & lysine
• Both glucogenic & ketogenic
e.g., Phenylalanine, Tyrosine, Tyrptophan, Isoleucine

16. Urea cycle
• 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 liver.

18. I step
• 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
synthetase I.

19. II Step
• 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
ornithine transcarbamoylase.
 Citrulline passes from the mitochondrion to the cytosol.

20. III Step
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,
requires ATP.

21. IV Step
• Argininosuccinate is then cleaved by argininosuccinase to form free
arginine and fumarate
• fumarate enters mitochondria to join the pool of citric acid cycle
intermediates.

22. V Step
• Arginase cleaves arginine to yield urea and ornithine.
• Ornithine is transported into the mitochondrion to
initiate another round of the urea cycle.

23. Link between Urea Cycle & Kreb Cycle

24. Amino Acid Degradation

25. Amino Acid Degrading to �-Ketoglutarate

26. Glutamic Acid:
• catalysed by glutamate dehydrogenase

27. Glutamine:
Glutamine glutaminase Glutamate + NH3
Proline:
N
+
HH
OOC Proline oxidase N
+
H
OOC
Pyrroline 5 carboxylate
H2O
H
O
NH3
+
C
O
O
-
Glutamate Gamma-semialdehyd
Glutamate
5-semialdehyde
dehydrogenase
Glutamate

28. Arginine:
Ornithine aminotransferase
CH
O
(CH2 )3
NH2
COOH
NH2
NH
NH (CH2 )3
NH2
COOH
NH2 (CH2 )3
NH2
COOH
Glu-5-semiald.
DH
Glutamate

29. Histidine:
 Here glutamate foriminotransferase transfer the
forimino group to THF
NHN
CH2
COOH
NH2
N NH
CH
COOH
NHN
O
COOH
NH NH
HOOC
COOH
histidine
ammonia
lyase
Uroconate
4-imidazolone-5-propionate
Uroconate hydratase
imidazolone propionase
N-foriminoglutamate
Glutamate foriminotransferase
Glutamate + N5
-forimino-THF
H2O

30. Amino Acids Degrading to Succinyl Co A

31. How Propionyl CoA converting to Succinyl CoA
I step enzyme- Propionyl CoA carboxylase
II step enzyme- Mutase

32. Valine:
CH
NH2
COOH
O
COOH
O
S CoA
CH2 C
CH3
O
S CoA
CH2 CH
CH3
O
S CoA
OH
CH2 CH
CH3
COOH
OH
CH CH
CH3
COOH
O
CH2
CH3
O
S CoA
Valine transaminase
alpha KGA Glu
CoA
CO2
NAD
NADH+ H+
alpha-keta isovaleric acid
alpha-keta isovaleric
acid DH
isobutaryl CoA
isobutaryl CoA DH
enoyl CoA hydratase
Beta hydroxy butyric acid
Dehydogenase
H2 O
PLP
CoA
CO2
CoA
Propionyl CoA
Methyl Malonic acid semialdehyde

35. Amino Acids Degrading to Acetyl CoA &
Acetoacetate

38. Tryptophan:

39. Amino Acids Degrading to Oxaloacetic Acid

40. Asparagine and Aspartic Acid:
Catalysed by aspartate amino transferase.
COOH
CHNH2
CH2
O
NH2
COOH
CHNH2
CH2
COOH
Asparagine
Asparaginase
H2O N+
H4
Aspartic acid

41. Amino Acids Degrading to Pyruvic Acid

42. Alanine:
Catalysed by alanine amino transferase

43. Serine:
Serine dehyratase also requires a pyridoxal phosphate
cofactor.
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
pyruvate.
CH COOH
CH2
NH2
OH
NH2 C
CH2
COOH
NH C
CH3
COOH
CH3 C
O
COOH
Ser
Ser. dehydratase
imine
NH3
H2O
Pyruvic Acid
Tautomerization
Amino acrylate

44. References
• Principles of Biochemistry, Lehninger
• Concise Textbook of Chemistry, G.Rajagopal
• www.tamu.edu/faculty/bmiles/lectures/amcat
.pdf - United States
• www.rpi.edu/dept/bcbp/molbiochem/MBWeb/
mb2/.../aacarbon.htm
• www.bmb.leeds.ac.uk/illingworth/metabol/ami
no.htm