15' Amino acid metabolism: transamination

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15. Amino acid metabolism transamination
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Most mammals convert amino-acid nitrogen to urea
for excretion
amino acids
The carbon chains are broken down to molecules
that feed into the TCA cycle.
NH4
Some animals excrete NH4 or uric acid.
NH4 ammonium ion
uric acid
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The first step in catabolism of most amino acids
is transamination
?-keto acid
amino acid
?-ketoglutarate
glutamate
The main function of transamination is to funnel
amino groups into a small number of amino acids,
particularly Glu Asp. Some amino transferases
(transaminases) are specific for
a-ketoglutarate and Glu others use oxaloacetate
and Asp.
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Transaminases use pyridoxal phosphate as a
prosthetic group
pyridoxal phosphate forms a Schiff base
(aldimine) bond to a lysine residue of the enzyme
pyridoxal phosphate
pyridoxine hydrochloride (vitamin B6)
pyridoxamine phosphate
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Pyridoxal phosphate transfers the amino group by
shuttling between aldehyde and amine forms
amino acid 1
?-keto acid 1
CH2NH3
pyridoxal phosphate (on enzyme)
pyridoxamine phosphate (on enzyme)
-O2C C R2
amino acid 2
?-keto acid 2
O
Both steps occur with the coenzyme bound to the
same enzyme molecule. This is a classic
ping-pong enzyme mechanism.
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The positive charge of the pyridoxine ring
facilitates interconversions of Schiff-base
intermediates
H2O
Schiff base
H
amino acid
N
..
CH
H
pyridoxal phosphate
H
H2O
H
?-keto acid
CH2
CH2NH2
pyridoxamine phosphate
Schiff base
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The active site has additional residues that
could facilitate proton binding and release
Arg 222
Lys 258
Asn 194
Schiff base formed from PLP 2-methyl-Asp
aspartate aminotransferase
Asp 222
1ajs.pdb
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Related enzymes use pyridoxal phosphate to
catalyze amino acid racemizations and
decarboxylations
Schiff base
H2O
CO2
amino acid
CH
H C R
H2O
amine
Schiff base
H
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Amino acid decarboxylases generate amines that
serve as neurotransmitters
Glu
5-hydroxy-Trp
Dihydroxy-Phe (DOPA)
CO2
CO2
CO2
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The amino groups of glutamic acid and glutamine
can be released as ammonia in liver mitochondria
cellular protein
ingested protein
transaminases
a-keto acids
amino acids
?-keto-glutarate
Glu
glutamate dehydrogenase
NADH or NADPH H
H2O
NAD or NADP
Gln from muscle other tissue
But ammonia is toxic, particularly to neural
tissue. Organisms must get rid of it.
NH4
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Alanine carries amino groups from muscle to the
liver for excretion
muscle protein
blood
liver
muscle
glucose
glucose
urea
amino acids
NH4
Glu
Glu
pyruvate
pyruvate
a-keto- glutarate
a-keto- glutarate
Ala
Ala