Amino Acid Catabolism: N: Molecular Biochemistry II
Amino Acid Catabolism: N: Molecular Biochemistry II
Amino Acid Catabolism: N: Molecular Biochemistry II
H
R1 C COO
R2
NH3
Transaminases
(aminotransferases)
catalyze the
reversible reaction
at right.
C COO
O
Transaminase
H
R1 C COO
O
R2
C COO
NH3
COO
COO
COO
CH2
COO
CH2
CH2
CH2
CH2
CH2
HC
NH3+
COO
COO
COO
HC
NH3+
COO
Aminotransferase (Transaminase)
CH3
HC
COO
COO
CH2
CH2
CH2
NH3+
COO
CH3
O
COO
alanine a-ketoglutarate
CH2
O
COO
pyruvate
HC
NH3+
COO
glutamate
Aminotransferase (Transaminase)
Tryptophan
Phenylalanine (Tyr can be made from Phe.)
Methionine (Cys can be made from Met.)
Histidine (Essential for infants.)
H
O
O
P
O
O
C
H2
C
OH
N
H
CH3
H
C
COO
Enz
(CH2)4
NH2
Amino acid
N+
HC
H2
C
P
O
H
O
N
H
CH3
EnzLysNH2
H
C
COO
N+
HC
H2
C
P
O
H
O
N
H
CH3
O
EnzLysNH2
H2
C
P
O
What was an
amino acid
leaves as an
a-keto acid.
CH2
NH2
COO
a-keto acid
OH
N
CH3
H
Pyridoxamine phosphate (PMP)
EnzLysNH2
H
C
COO
N+
HC
H2
C
P
O
H
O
N
H
CH3
Chime Exercise
Two neighboring students or student groups should
team up, each displaying one of the following:
Transaminase with PLP in Schiff base linkage to
the active site lysine residue.
Transaminase in the PMP form, with glutarate, an
analog of a-ketoglutarate, at the active site.
OOC
Glutamate
Dehydrogenase
catalyzes a major
reaction that effects
net removal of N
from the amino
acid pool.
H2
C
H2
C
glutamate
NH3+
C
H
H2O
COO
NAD(P)+
NAD(P)H
O
H2 H2
OOC C C
a-ketoglutarate
COO + NH4+
Glutamate Dehydrogenase
Amino acid
a-ketoglutarate
a-keto acid
glutamate
Transaminase
NADH + NH4
NAD + H2O
Glutamate
Dehydrogenase
Summarized above:
The role of transaminases in funneling amino N to
glutamate, which is deaminated via Glutamate
Dehydrogenase, producing NH4+.
+
H2O NH4
H2O
HO
CH2
H
C
COO
NH3+
serine
H2C
COO
H3C
COO
NH3+
aminoacrylate
pyruvate
Serine Dehydratase
O
H 2N
NH2
urea
HCO 3
Carbamoyl Phosphate
Synthase (Type I) catalyzes
a 3-step reaction, with
carbonyl phosphate and
carbamate intermediates.
ATP
ADP
O
HO
carbonyl phosphate
NH3
Pi
OPO32
H2N
carbamate
ATP
ADP
O
H2N
OPO32
carbamoyl phosphate
HCO 3
Alternate forms of
Carbamoyl Phosphate
Synthase (Types II & III)
initially generate ammonia
by hydrolysis of glutamine.
ATP
ADP
O
HO
OPO32
carbonyl phosphate
NH3
Pi
O
H2N
carbamate
ATP
ADP
O
H2N
OPO32
carbamoyl phosphate
O
H2N
Carbamoyl Phosphate
Synthase
OPO 32 + 2 ADP + Pi
carbamoyl phosphate
glutamate (Glu)
N-acetylglutamate
H
H3N+
COO
H3C
H
N
H
COO
CH2
CH2
CH2
CH2
COO
COO
O
NH3+
Urea Cycle
CH2
NH3+
NH
COO
ornithine
4
H2O
citrulline
CH2
Pi
CH2
COO
urea
NH2
3
COO
CH2
HC
CH2
HC
HC
H
N
COO
NH
arginine
CH
NH3+
COO
NH2
COO
aspartate
CH2
CH2
HC
NH2+
H2N
CH2
ATP
AMP + PPi
COO
H2N
COO
NH3+
HC
Urea Cycle
NH2
CH2
CH2
HC
OPO32
carbamoyl
phosphate
CH2
Enzymes in
mitochondria:
1. Ornithine
Transcarbamylase
Enzymes in
cytosol:
2. ArgininoSuccinate
Synthase
3. Argininosuccinase
4. Arginase.
H2N
COO
fumarate
NH2+
NH
CH2
CH2
argininosuccinate
CH2
HC
NH3+
COO
cytosol
mitochondrial matrix
carbamoyl phosphate
Pi
ornithine
citrulline
ornithine
urea
arginine
citrulline
aspartate
argininosuccinate
fumarate
cytosol
mitochondrial matrix
carbamoyl phosphate
Pi
ornithine
citrulline
ornithine
urea
arginine
citrulline
aspartate
argininosuccinate
fumarate
COO
COO
COO
CH2
COO
CH2
CH2
CH2
CH2
CH2
HC
NH3+
COO
COO
COO
HC
NH3+
COO
Aminotransferase (Transaminase)
cytosol
The complete
Urea Cycle is
significantly only
in liver.
mitochondrial matrix
carbamoyl phosphate
Pi
ornithine
citrulline
However some
ornithine
citrulline
urea
aspartate
enzymes of the
arginine
argininosuccinate
pathway are in
fumarate
other cells and
tissues where they generate arginine & ornithine, which
are precursors for other important molecules.
E.g., Argininosuccinate Synthase, which catalyzes
synthesis of the precursor to arginine, is in most tissues.
Mitochondrial Arginase II, distinct from the cytosolic
Urea Cycle Arginase, cleaves arginine to yield ornithine.
arginine (Arg)
H
H3N+
COO
CH2
CH3
CH2
H2N
CH2
CH2
NH2+
NH
O
C
O
creatine
NH2
NH2
NH2
C
NH2
NH
C
NADPH
NADP+
CH2
O2
CH
OH
CH2
O2
arginine
H3 N
CH
NO
CH2
H2O
CH2
CH2
COO
NH
CH2
H2O
CH2
H3N
NH
CH2
CH2
NH2
NH2
COO
hydroxyarginine
H3N
CH
COO
citrulline
H3N CH2
CH2
CH2
CH2
H3N
CH2
CH2
NH
CH2
NH3+
CH2
putrescine
CH2
CH2
CH2
NH3+
spermidine
H
H3N+
COO
CH2
CH2
CH2
NH3
ornithine
H3N CH2
CH2
CH2
CH2
H3N
CH2
CH2
NH
CH2
NH3+
CH2
putrescine
CH2
CH2
CH2
NH3+
spermidine
H
H3N+
H
COO
H3N+
CH2
CH2
CH2
CH2
CH2
CH2
NH
NH
COO
NH2
NH2
arginine
NH2
citrulline
H
H3N+
Substitution of citrulline,
which lacks arginine's
positive charge, may alter
structure & properties such as
binding affinities of a protein.
H
COO
H3N+
CH2
CH2
CH2
CH2
CH2
CH2
NH
NH
COO
NH2
NH2
NH2
O
E.g., citrullination of certain
arginine
citrulline
proteins, including keratin
intermediate filament proteins,
is essential to terminal differentiation of skin cells.