Amino acid metabolism 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. Metabolism of amino acids differs, but 3 common reactions: – Transamination – Deamination – Decarboxylation
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Amino acid metabolism - JSMU Lecture... · Transamination In transamination • Amino acids are degraded in the liver. • An amino group is transferred from an amino acid to an -keto
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Amino acid metabolism
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.
Metabolism of amino acids differs, but 3 common reactions:
– Transamination
– Deamination
– Decarboxylation
2
Transamination
In transamination
• Amino acids are degraded in the liver.
• An amino group is transferred from an amino acid
to an -keto acid, usually -ketoglutarate.
• The reaction is catalyzed by a transaminase or
aminotransferase.
•
• A new amino acid, usually glutamate, and a new
-keto acid are formed.
Transamination reactions
Enzymatic Transamination
• Typically, -ketoglutarate
accepts amino groups
• L-Glutamine acts as a
temporary storage of nitrogen
• L-Glutamine can donate the
amino group when needed for
amino acid biosynthesis
• All aminotransferases rely on
the pyridoxal phosphate
cofactor
Amino Group Transfer - Aminotransferase
Enzymatic removal of -amino groups (transaminase
/aminotransferases - named for amino donor
i.e. Ala aminotranferase removes amino group from Ala)
• Ping-pong
kinetics of
aspartate
transaminase (next slide)
(from previous slide)
Transamination
The 3-C -keto acid pyruvate is produced from alanine, cysteine, glycine, serine, & threonine.
Alanine deamination via Transaminase directly yields pyruvate.
alanine -ketoglutarate pyruvate glutamate
Aminotransferase (Transaminase)
COO
CH2
CH2
C
COO
O
CH3
HC
COO
NH3+
COO
CH2
CH2
HC
COO
NH3+
CH3
C
COO
O + +
The 4-C Krebs Cycle intermediate oxaloacetate is produced from aspartate & asparagine.
Aspartate transamination yields oxaloacetate.
Aspartate is also converted to fumarate in Urea Cycle. Fumarate is converted to oxaloacetate in Krebs cycle.
aspartate -ketoglutarate oxaloacetate glutamate
Aminotransferase (Transaminase)
COO
CH2
CH2
C
COO
O
COO
CH2
HC
COO
NH3+
COO
CH2
CH2
HC
COO
NH3+
COO
CH2
C
COO
O + +
The Amino
Group is
Removed
From All
Amino
Acids First
12
Oxidative Deamination
Oxidative deamination
• Removes the amino group as an
ammonium ion from glutamate.
• Provides -ketoglutarate for
transamination.
Oxidative Deamination • Glutamate formed by transamination reactions
is deaminated to -ketoglutarate
• Glutamate dehydrogenase - NAD+ or NADP+ is coenzyme
• Other AA oxidases - (liver, kidney) low activity
It is one of the few enzymes that can use NAD+ or NADP+ as e acceptor.
Oxidation at the -carbon is followed by hydrolysis, releasing NH4
+.
OOC
H2
CH2
C C COO
O
+ NH4+
NAD(P)+
NAD(P)H
OOC
H2
CH2
C C COO
NH3+
Hglutamate
-ketoglutarate
Glutamate Dehydrogenase
H2O
Glutamate Dehydrogenase catalyzes a major reaction that effects net removal of N from the amino acid pool.
Summarized above:
The role of transaminases in funneling amino N to glutamate, which is deaminated via Glutamate Dehydrogenase, producing NH4
+.
Amino acid -ketoglutarate NADH + NH4+
-keto acid glutamate NAD+ + H2O
Transaminase Glutamate Dehydrogenase
Non-oxidative deamination
• 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.
DEAMIDATION
• The amino acid, which contains an amide
linkage with ammonia at the γ-carboxyl,
degraded by process of deamidation.
• E.g, conversion of asparagine to aspartate
by removal of alpha amino group.
Decarboxylation
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.
Transmethylation
• Resynthesis of methionine:
• Homocysteine accepts a methyl group from N5-
methyltetrahydrofolate (N5-methyl-THF)
requiring methylcobalamin, a coenzyme derived
from vitamin B12.
•
• The methyl group is transferred from the B12
derivative to homocysteine, and cobalamin is
• recharged from N5-methyl-THF.
Excretory
Forms of
Nitrogen
Fate of Individual Amino Acids
• Seven to acetyl-CoA – Leu, Ile, Thr, Lys, Phe, Tyr, Trp
• Six to pyruvate – Ala, Cys, Gly, Ser, Thr, Trp
• Five to -ketoglutarate – Arg, Glu, Gln, His, Pro