Amino acid metabolism
• Metabolism of amino acids differs, but 3
common reactions:
– Transamination
– Deamination
– Decarboxylation
• All transaminases require pyridoxal
phosphate, a coenzyme derived from Vitamin
B6.
• No free NH3 , only the transfer of amino group
occurs.
• Transamination is reversible.
• Glutamate is the only amino acid that
undergoes oxidative deamination to a
significant extent to liberate free NH3 for urea
synthesis.
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.
3
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 (next slide)
transaminase
(from previous slide)
Transamination
COO COO
CH2 CH2
CH3 CH2 CH3 CH2
HC N H 3+ + C O C O + HC N H 3+
COO COO COO COO
a la n in e -k e to g lu ta ra te p y r u v a te g lu ta m a t e
A m in o t r a n s f e r a s e ( T r a n s a m in a s e )
The 3-C -keto acid pyruvate is produced from
alanine, cysteine, glycine, serine, & threonine.
Alanine deamination via Transaminase directly
yields pyruvate.
COO COO
COO CH2 COO CH2
CH2 CH2 CH2 CH2
HC N H 3+ + C O C O + HC N H 3+
COO COO COO COO
a s p a r ta t e -k e to g lu t a r a te o x a lo a c e ta te g l u t a m a te
A m in o tr a n s f e r a s e ( T r a n s a m in a s e )
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.
The Amino
Group is
Removed
From All
Amino
Acids First
Oxidative Deamination
Oxidative deamination
• Removes the amino group as an
ammonium ion from glutamate.
• Provides -ketoglutarate for
transamination.
13
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
N H 3+
H2 H2
OOC C C C COO
Glutamate glutam ate
H +
N A D (P )
Dehydrogenase H 2O
N AD(P)H
catalyzes a major
O
reaction that H2 H2
effects net OOC C C C C O O + N H 4+
removal of N -ketoglutarate
from the amino G lutam ate D ehydrogenase
acid pool.
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+.
Amino acid -ketoglutarate NADH + NH4+
-keto acid glutamate NAD+ + H2O
Transaminase Glutamate
Dehydrogenase
Summarized above:
The role of transaminases in funneling amino N
to glutamate, which is deaminated via Glutamate
Dehydrogenase, producing NH4+.
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
• Four to succinyl-CoA
– Ile, Met, Thr, Val
• Two to fumarate
– Phe, Tyr
• Two to oxaloacetate
– Asp, Asn
Summary
of Amino
Acid
Catabolis
m
