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Degradation of Amino Acids
Presented By:
Anuradha Verma
What are amino acids?
Proteins are polymers of amino acids, with each amino acid residue joined to
its neighbor by a speci...
• 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 contai...
Degradation of Amino
Acids
During degradation amino acids lose their NH2
group to form �-keto acids, the c-skeleton of
amino acids.
�-keto acids on o...
Metabolic Fate of Amino Acid
Amino acid from
ingested protein
Cellular Protein
Amino acid
Alpha keto
acid
Alpha keto
gluta...
• Ammonotelic:
Releases ammonia as excretory product.
e.g., aquatic vertebrates, bony fishes and larvae
of amphibia.
• Ure...
Transamination reaction
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 leavin...
It undergoes reversible
transformations between
1- aldehyde form
(pyridoxal phosphate)
-which can accept an amino
group an...
Reactions at the �- carbon include-
• racemizations (interconverting L- and D-amino acids)
• Decarboxylations
• transamina...
Glutamate Releases Its Amino Group
as Ammonia in the Liver
Amino groups from many of the amino acids are
collected in the ...
Classification of amino acid on the basis of their
end products
• Glucogenic
Glucogenic amino acids are those that give ri...
Urea cycle
• In ureotelic organisms, the ammonia
deposited in the mitochondria of hepatocytes
is converted to urea in the ...
I step
• The first amino group to enter the urea cycle is derived from
ammonia in the mitochondrial matrix—NH4
+
• The NH4...
II Step
• The carbamoyl phosphate functions as an activated carbamoyl group
donor enters the urea cycle.
• Carbamoyl phosp...
III Step
Second amino group now enters from aspartate (generated in mitochondria by
transamination and transported into th...
IV Step
• Argininosuccinate is then cleaved by argininosuccinase to form free
arginine and fumarate
• fumarate enters mito...
V Step
• Arginase cleaves arginine to yield urea and ornithine.
• Ornithine is transported into the mitochondrion to
initi...
Link between Urea Cycle & Kreb Cycle
Amino Acid Degradation
Amino Acid Degrading to �-Ketoglutarate
Glutamic Acid:
• catalysed by glutamate dehydrogenase
Glutamine:
Glutamine glutaminase Glutamate + NH3
Proline:
N
+
HH
OOC Proline oxidase N
+
H
OOC
Pyrroline 5 carboxylate
H2O...
Arginine:
Ornithine aminotransferase
CH
O
(CH2 )3
NH2
COOH
NH2
NH
NH (CH2 )3
NH2
COOH
NH2 (CH2 )3
NH2
COOH
Glu-5-semiald.
...
Histidine:
 Here glutamate foriminotransferase transfer the
forimino group to THF
NHN
CH2
COOH
NH2
N NH
CH
COOH
NHN
O
COO...
Amino Acids Degrading to Succinyl Co A
How Propionyl CoA converting to Succinyl CoA
I step enzyme- Propionyl CoA carboxylase
II step enzyme- Mutase
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...
Amino Acids Degrading to Acetyl CoA &
Acetoacetate
Tryptophan:
Amino Acids Degrading to Oxaloacetic Acid
Asparagine and Aspartic Acid:
Catalysed by aspartate amino transferase.
COOH
CHNH2
CH2
O
NH2
COOH
CHNH2
CH2
COOH
Asparagin...
Amino Acids Degrading to Pyruvic Acid
Alanine:
Catalysed by alanine amino transferase
Serine:
Serine dehyratase also requires a pyridoxal phosphate
cofactor.
β-elimination of the hydroxyl group of serine to f...
References
• Principles of Biochemistry, Lehninger
• Concise Textbook of Chemistry, G.Rajagopal
• www.tamu.edu/faculty/bmi...
Degradation of amino acids
Degradation of amino acids
Degradation of amino acids
Degradation of amino acids
Degradation of amino acids
Degradation of amino acids
Degradation of amino acids
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Degradation of amino acids

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Degradation of amino acids

  1. 1. Degradation of Amino Acids Presented By: Anuradha Verma
  2. 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. 3. • Asparagine was the first discovered amino acid in 1806. • The last discovered was threonine in 1938.
  4. 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
  5. 5. Degradation of Amino Acids
  6. 6. 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
  7. 7. 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
  8. 8. • 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
  9. 9. Transamination reaction Most common amino acids can be converted into the corresponding keto acid by transamination.
  10. 10. 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.
  11. 11. 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
  12. 12. 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.
  13. 13. 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
  14. 14. 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
  15. 15. 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.
  16. 16. 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.
  17. 17. 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.
  18. 18. 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.
  19. 19. 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.
  20. 20. V Step • Arginase cleaves arginine to yield urea and ornithine. • Ornithine is transported into the mitochondrion to initiate another round of the urea cycle.
  21. 21. Link between Urea Cycle & Kreb Cycle
  22. 22. Amino Acid Degradation
  23. 23. Amino Acid Degrading to �-Ketoglutarate
  24. 24. Glutamic Acid: • catalysed by glutamate dehydrogenase
  25. 25. 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
  26. 26. 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
  27. 27. 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
  28. 28. Amino Acids Degrading to Succinyl Co A
  29. 29. How Propionyl CoA converting to Succinyl CoA I step enzyme- Propionyl CoA carboxylase II step enzyme- Mutase
  30. 30. 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
  31. 31. Amino Acids Degrading to Acetyl CoA & Acetoacetate
  32. 32. Tryptophan:
  33. 33. Amino Acids Degrading to Oxaloacetic Acid
  34. 34. 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
  35. 35. Amino Acids Degrading to Pyruvic Acid
  36. 36. Alanine: Catalysed by alanine amino transferase
  37. 37. 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
  38. 38. 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

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