Amino Acid Metabolism.ppt definition and

definition

1. AMINO ACID METABOLISM
Dr Sajad Ahmad Bhat
Department of Biochemistry

2. Amino acid structure

3. The 20 common amino acids of proteins

4. Metabolic relationship of amino acids
BODY PROTEINS
Proteosynthesis Degradation
AMINO ACIDS
DIETARY
PROTEINS
GLYCOLYSIS
KREBS CYCLE
Digestion
T
ran
sam
in
ation
NONPROTEIN
DERIVATIVES
Porphyrins
Purines
Pyrimidines
Neurotransmitters
Hormones
Komplex lipids
Aminosugars
UREA NH
3
C
o
n
v
e
r
s
i
o
n
(
C
a
r
b
o
n

s
k
e
l
e
t
o
n
)
250 – 300
g/day
ACETYL CoAGLUCOSE CO
2
KETONBODIES

5. Endopeptidases – hydrolyse the peptide bond inside a
chain: pepsin, trypsin, chymotrypsin
Exopeptidases – split the peptide bond at the end of a
protein molecule: aminopeptidase, carboxypeptidases
Dipeptidases
Enzymes cleaving the peptide bond
pepsin (pH 1.5 – 2.5) – peptide bond derived from Tyr, Phe,
bonds between Leu and Glu
trypsin (pH 7.5 – 8.5) – bonds between Lys a Arg
chymotrypsin (pH 7.5 – 8.5) – bonds between Phe a Tyr

6. Essential amino acids in humans
Arginine*
Histidine*
Isoleucine
Leucine
Valine
Lysine
Methionine
Threonine
Phenylalanine
Tryptophan
*Required to some degree in young growing period and/or sometimes during illness.

7. Non-essential and nonessential
amino acids in humans
Alanine
Asparagine
Aspartate
Glutamate
Glutamine
Glycine
Proline
Serine
Cysteine (from Met*)
Tyrosine (from Phe*)
* Essential amino acids
Can be formed from -keto acids by transamination and
subsequent reactions.

8. C
O
R COO
-
+NH
4
+
deamination
transamination
C
O
R COO
-
CH
NH
2
R COO
-
CH
NH
2
R COO
-
oxidative
decarboxylation
CH
2
NH
3
+
R CO
2+
General reactions of amino acid catabolism

9. The fate of the amino group during amino acid catabolism

10. Transamination reaction
The first step in the catabolism of most amino acids is
removal of a-amino groups by enzymes transaminases
or aminotransferases
All aminotransferases have the same prostethic group and
the same reaction mechanism.
The prostethic group is pyridoxal phosphate (PPL),
the coenzyme form of pyridoxine (vitamin B
6)

11. Biosynthesis of amino acid:
transamination reactions
amino acid
1
keto acid
2
amino acid
2
+-keto acid
1

NH
3
+
-
O
2CCH
2CH
2CHCO
2
-
Glutamate
O
R-CCO
2
-+
O
-
O
2CCH
2CH
2CCO
2
-
-Ketoglutarate
NH
2
R-CHCO
2
-
+
Pyridoxal phosphate (PLP)-
dependent aminotransferase
Keto-acid
Amino acid

12. Active metabolic form of vitamin B
6

13. Mechanism of transamination reaction: PPL complex with enzyme accept
an amino group to form pyridoxamine phosphate, which can donate its amio
group to an -keto acid.

14. All amino acids except threonine, lysine, and
proline can be transaminated
Transaminases are differ in their specificity for L-
amino acids.
The enzymes are named for the amino group donor.

15. Clinicaly important transaminases
ALT
Alanine--ketoglutarate transferase ALT
(also called glutamate-pyruvate transaminase – GPT)
Aspartate--ketoglutarate transferase AST
(also called glutamate-oxalacetate transferase – GOT)
Important in the diagnosis of heart and liver damage caused by heart
attack, drug toxicity, or infection.

16. Glucose-alanine cycle
Ala is the carrier of ammonia and of the carbon
skeleton of pyruvate from muscle to liver.
The ammonia is excreted and the pyruvate is
used to produce glucose, which is returned to
the muscle.
Alanine plays a special role in
transporting amino groups to liver.
According to D. L. Nelson, M. M. Cox :LEHNINGER. PRINCIPLES OF BIOCHEMISTRY Fifth edition

17. Glutamate releases its amino group as
ammonia in the liver
The amino groups from many of the a-amino acids are collected in the
liver in the form of the amino group of L-glutamate molecules.
 Glutamate undergoes oxidative deamination catalyzed by L-glutamate
dehydrogenase.
 Enzyme is present in mitochondrial matrix.
 It is the only enzyme that can use either NAD
+
or NADP
+
as the acceptor of reducing
equivalents.
 Combine action of an aminotransferase and glutamate dehydrogenase referred to as
transdeamination.

18. Ammonia transport in the form of glutamine
Glutamine
synthetase
Excess ammonia is added to
glutamate to form glutamine.
Glutamine enters the liver and NH
4
+

is liberated in mitochondria by the
enzyme glutaminase.
Ammonia is remove by urea
synthesis.

19. Relationship between glutamate, glutamine
and -ketoglutarate
-ketoglutarate glutamate glutamine
NH
3
NH
3
NH
3
NH
3
glutamate+NAD
+
+
H
2
O -ketoglutarate NH
3+ +NADH
glutamate NH
3+
glutamine
ATP ADP
glutamine H
2
O+ glutamate NH
3+
A. Glutamate dehydrogenase
B. Glutamine synthetase (liver)
C. Glutaminase (kidney)
From transamination
reactions
To urea cycle

20. Oxidative deamination
Amino acids FMN H
2
O+ +
keto acids FMNH
2
NH
3
L-amino acid oxidase
A. Oxidative deamination
FMN H
2
O
2
H
2
O O
2
+
+ +
O
2
catalse
B. Nonoxidative deamination
serine
pyruvate
threonine
-ketoglutateNH
3
+
+
NH
3
Serin-threonin dehydratase
•L-amino acid oxidase produces
ammonia and -keto acid directly,
using FMN as cofactor.
•The reduced form of flavin must be
regenerated by O
2
molecule.
•This reaction produces H
2
O
2

molecule which is decompensated by
catalase.
Is possible only for hydroxy amino acids

21. Amino acid metabolism and central
metabolic pathways
20 amino acids are converted
to 7 products:
 pyruvate
 acetyl-CoA
 acetoacetate
 -ketoglutarate
 succynyl-CoA
 oxalacetate
 fumarate

22. Glucogenic Amino Acids
formed: -ketoglutarate, pyruvate,
oxaloacetate, fumarate, or succinyl-CoA
Aspartate
Asparagine
Arginine
Phenylalanine
Tyrosine
Isoleucine
Methionine
Valine
Glutamine
Glutamate
Proline
Histidine
Alanine
Serine
Cysteine
Glycine
Threonine
Tryptophan

23. Ketogenic Amino Acids
formed acetyl CoA or acetoacetate
Lysine
Leucine

24. Both glucogenic and ketogenic amino
acids
formed: -ketoglutarate, pyruvate,
oxaloacetate, fumarate, or succinyl-CoA in
addition to acetyl CoA or acetoacetate
Isoleucine
Threonine
Tryptophan
Phenylalanine
Tyrosine

25. Alanine
Serine
Cysteine
Threonine
The C3 family: alanine, serine, cysteine and
threonine are converted to pyruvate
Pyruvate

26. The C4 family: aspartate and asparagine are
converted into oxalacetate
Aspartic acid Asparagine
Oxalacetate

27. The C5 family: several amino acids are converted into
-ketoglutarate through glutamate
Glutamine
Proline
Histidine
Arginine
ketoglutarate

28. Interconversion of amino acids and intermediates of
carbohydrate metabolism and Krebs cycle

29. Metabolism of some selected
amino acids

30. Serine biosynthesis from glycolytic
intermediate 3-phosphoglycerate
Copy from: http://themedicalbiochemistrypage.org/amino-acid-metabolism.html

31. Glycine biosynthesis from serine
Reaction involves the transfer of the hydroxymethyl group from serine to the cofactor
tetrahydrofolate (THF), producing glycine and N
5
,N
10
-methylene-THF.
Copy from: http://themedicalbiochemistrypage.org/amino-acid-metabolism.html

32. Glycine oxidation to CO
2
Glycine produced from serine or from the diet can also be oxidized by glycine
decarboxylase (also referred to as the glycine cleavage complex, GCC) to yield a
second equivalent of N
5
,N
10
-methylene-tetrahydrofolate as well as ammonia and
CO
2
.
Copy from: http://themedicalbiochemistrypage.org/amino-acid-metabolism.html

33. The sulfur for cysteine synthesis comes from the essential amino acid
methionine.
SAM serves as a precurosor for numerous methyl transfer reactions (e.g. the
conversion of norepinephrine to epinenephrine).
Cysteine and methionine are metabolically
related
Condensation of ATP and methionine
yield S-adenosylmethionine (SAM)
SAM

34. Cysteine synthesis
Copy from: http://themedicalbiochemistrypage.org/amino-acid-metabolism.html
1.Conversion of SAM to
homocysteine.
2.Condensation of
homocysteine with serine to
cystathione.
3.Cystathione is cleavaged to
cysteine.
Conversion of homocysteine back to Met.
N
5
-methyl-THF is donor of methyl group.
*
*folate + vit B
12

35. Genetic defects for both the synthase and the lyase.
Missing or impaired cystathionine synthase leads to homocystinuria.
High concentration of homocysteine and methionine in the urine.
Homocysteine is highly reactive molecule.
Disease is often associated with mental retardation, multisystemic
disorder of connective tissue, muscle, CNS, and cardiovascular
system.
Homocystinuria

36. Biosynthesis of Tyrosine from Phenylalanine
Phenylalanine hydroxylase is a mixed-function oxygenase: one atom of oxygen is
incorporated into water and the other into the hydroxyl of tyrosine. The reductant is the
tetrahydrofolate-related cofactor tetrahydrobiopterin, which is maintained in the reduced
state by the NADH-dependent enzyme dihydropteridine reductase

37. Hyperphenylalaninemia - complete deficiency of phenylalanine
hydroxylase (plasma level of Phe raises from normal 0.5 to 2 mg/dL to
more than 20 mg/dL).
The mental retardation is caused by the accumulation of
phenylalanine, which becomes a major donor of amino groups in
aminotransferase activity and depletes neural tissue of α-
ketoglutarate.
Absence of α-ketoglutarate in the brain shuts down the TCA cycle and
the associated production of aerobic energy, which is essential to
normal brain development.
Newborns are routinelly tested for blood concentration of Phe.
The diet with low-phenylalanine diet.
Phenylketonuria

38. valine isoleucine leucine
-ketoglutarate glutamate (transamination)
-ketoisovalerate -keto--methylbutyrate -ketoisokaproate
oxidative decarboxylation
Dehydrogenase of -keto acids*
CO
2
NAD
+
NADH + H
+
isobutyryl CoA -methylbutyryl CoA isovaleryl CoA
Dehydrogenation etc., similar to fatty acid -oxidation
propionyl CoA
acetyl CoA
acetoacetate
acetyl CoA
propionyl CoA
+ +
Catabolism of branched amino acids

39. Branched-chain aminoaciduria
Disease also called Maple Syrup Urine Disease (MSUD) (because
of the characteristic odor of the urine in affected individuals).
Deficiency in an enzyme, branched-chain α-keto acid
dehydrogenase leads to an accumulation of three branched-
chain amino acids and their corresponding branched-chain α-keto
acids which are excreted in the urine.
There is only one dehydrogenase enzyme for all three amino
acids.
Mental retardation in these cases is extensive.

40. Histidine Metabolism:
Histamine Formation
N
N
H
CH
2CHCO
2
-
NH
3
+
N
N
H
CH
2CH
2NH
2
Histidine Histamine
Histidine
decarboxylase
CO
2
Histamine:
Synthesized in and released by mast cells
Mediator of allergic response: vasodilation,
bronchoconstriction

41. Tryptophan catabolism
Tryptophan has complex catabolic pathway:
1.the indol ring is ketogenic
2.the side chain forms the glucogenic products
Kynurenate and xanthurenate are excrete in the urine.

42. Enzymes which metabolised amino acides
containe vitamines as cofactors
THIAMINE B
1
(thiamine diphosphate)
oxidative decarboxylation of -ketoacids
RIBOFLAVIN B
2 (flavin mononucleotide FMN, flavin adenine dinucleotide
FAD)
oxidses of -aminoacids
NIACIN B
3
– nicotinic acid (nikotinamide adenine dinucleotide NAD
+
nikotinamide adenine dinukleotide phosphate NADP
+
)
dehydrogenases, reductase
PYRIDOXIN B
6 (pyridoxalphosphate)
transamination reaction and decarboxylation
FOLIC ACID (tetrahydropholate)
Meny enzymes of amino acid metabolism

43. http://themedicalbiochemistrypage.org/amino-acid-metabolism.html
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