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(CO
2
)
ATP
H
2
C C COO
OP
COOH
CH
2
C
O
COOH
Oxaloacetate
ADP + P
i
+
Pyruvate
Pyruvate
Carboxylase
Oxaloacetate
Phosphoenolpyruvate
(PEP)
Glucose
PEP
Carboxykinase
"Gluconeogenesis"
GTP GDP + CO
2
Degradation to Pyruvate
Alanine, Cysteine, Glycine,
Serine and Threonine
Alanine
+
H
3
N C
H
CH
3
COO
H
3
C C COO
O
aKG Glu
Alanine
Pyruvate
Alanine Aminotransferase
Cysteine
(Various Routes)
Glycine, Threonine and Serine
N CH
3
H
P
C
H N
H
O
C COO
H
Threonine
Glycine
Serine
"CH
2
" + H
2
O PLP
Serine > Pyruvate
Glycine > Serine
Serine Hydroxymethyl Transferase
Formation of Glycine-PLP
Schiff Base
N CH
3
H
P
C
H N
H
O
(CH
2
)
4
EnzymeB:
N CH
3
H
P
C
H N
H
O
C COO
H
EnzymeB: Lys
C COO
+
H
3
N
H
H
+
Glycine
Enzyme-PLP (Schiff Base) Glycine-PLP Schiff Base
a
"Transimination"
H
Formation of Ketimine
N CH
3
H
P
C
H N
H
O
C COO
H
EnzymeB: Lys
a
H
N CH
3
H
P
C
H N
H
O
C COO
H
EnzymeBH
+
Lys
N CH
3
H
P
C
H N
H
O
C COO
H
EnzymeBH
+
Lys
Formation of Serine
N CH
3
H
P
C
H N
H
O
C
COO
H
EnzymeBH
+
Lys
+
H
3
N C
H
COO
CH
2
OH
N
5
,N
10
-Methylene-THF
+
H
2
O
Enzyme-PLP
+
THF
Serine
Threonine > Serine
Serine Hydroxymethyl
Transferase
(PLP and CC Bond Cleavage)
Formation of Threonine-PLP
Schiff Base
N CH
3
H
P
C
H N
H
O
(CH
2
)
4
EnzymeB:
N CH
3
H
P
C
H N
H
O
C COO
H
C
H
H
3
C
O
H
EnzymeB: Lys
C COO
+
H
3
N
H
HC
CH
3
OH
+
Threonine
Enzyme-PLP (Schiff Base) Threonine-PLP Schiff Base
a
"Transimination"
Formation of Ketimine
N CH
3
H
P
C
H N
H
O
C COO
H
C
H
H
3
C
O
H
N CH
3
H
P
C
H N
H
O
C COO
H
H
3
C C
O
H
EnzymeBH
+
Lys
EnzymeB: Lys
N CH
3
H
P
C
H N
H
O
C COO
H
EnzymeBH
+
Lys
Formation of Serine
N CH
3
H
P
C
H N
H
O
C
COO
H
EnzymeBH
+
Lys
+
H
3
N C
H
COO
CH
2
OH
N
5
,N
10
-Methylene-THF
+
H
2
O
Enzyme-PLP
+
THF
Serine
Summary
N CH
3
H
P
C
H N
H
O
C COO
H
Threonine
Glycine
Serine
"CH
2
" + H
2
O PLP
N
5
, N
10
-Methylene Tetrahydrofolate
HN
N
N
H
N
H
2
C
N
O
H
2
N
C
O
N
H
CH
COO
n
5
10
CH
2
CH
2
C
O
OH
Glutamate
Source of
N
5
, N
10
-Methylene Tetrahydrofolate
Glycine Cleavage System
Glycine Decarboxylase Multienzyme Complex
or
Glycine Synthase (reverse direction)
Glycine Cleavage System
P-Protein: PLP-dependent glycine
decarboxylase
H-Protein: lipoamide-containing
protein
T-Protein: THF-requiring enzyme
L-Protein: NAD
+
-dependent FAD-
requiring dihydrolipoyl dehydrogenase
Glycine Cleavage System
(Formation of Glycine-PLP Schiff Base)
N CH
3
H
P
C
H N
H
O
(CH
2
)
4
EnzymeB:
N CH
3
H
P
C
H N
H
O
C COO
H
EnzymeB: Lys
C COO
+
H
3
N
H
H
+
Glycine
Enzyme-PLP (Schiff Base) Glycine-PLP Schiff Base
a
"Transimination"
H
Glycine Cleavage System
(Decarboxylation and Transfer of 1-Carbon Unit)
N CH
3
H
P
C
H N
H
O
C COO
H
H
N CH
3
H
P
C
H N
H
O
C H H
S
SH
H
S
SH
H
C
H
2
NH
2
CO
2
H
2
O
H
S
S
a
EnzymePLP
Glycine Cleavage System
(Formation of N
5
, N
10
-Methylene THF)
S
SH
H
C
H
2
NH
2
T THF
SH
SH
H
T N
5
, N
10
-MethyleneTHF
NAD
+
NADH + H
+
S
S
H
L-protein
NH
3
N
5
, N
10
-Methylene Tetrahydrofolate
HN
N
N
H
N
H
2
C
N
O
H
2
N
C
O
N
H
CH
COO
n
5
10
CH
2
CH
2
C
O
OH
Glutamate
Elimination of Water from Serine
Serine Dehydratase
Serine Dehydratase
(Formation of Serine-PLP Schiff Base)
Serine Dehydratase
(Formation of Aminoacrylate)
C COO
H
2
C
N CH
3
H
P
C
H N
H
O
C COO
H
2
C
O
H
N CH
3
H
P
C
H N
H
O
OH
H
2
C C COO
NH
2
Aminoacrylate
H
2
O PLP + H
+
Non-Enzymatic Step
(Conversion of Aminoacrylate to Pyruvate)
H
2
C C COO
NH
2
Aminoacrylate
H
3
C C COO
NH
2
H
2
O NH
4
+
H
3
C C
O
COO
Pyruvate
Tautomerization
Hydrolysis
H
+
[Imine]
Summary
N CH
3
H
P
C
H N
H
O
C COO
H
Threonine
Glycine
Serine
"CH
2
" + H
2
O PLP
Serine > Pyruvate
Degradation to Oxaloacetate
Asparagine and Aspartate
Asparagine > Aspartate >
Oxaloacetate
+
H
3
N C COO
H
H
2
C C
O
NH
2
H
2
O NH
4
+
Asparaginase
+
H
3
N C COO
H
H
2
C COO
Asparagine Aspartate
aKG Glu
GlutamateAspartate
Aminotransferase
O C COO
H
H
2
C COO
Oxaloacetate
Degradation to a-Ketoglutarate
Arginine, Glutamate,
Glutamine, Histidine and
Proline
Arginine and Proline
+
H
3
N C COO
H
(CH
2
)
3
NH
C
H
2
N NH
2
Arginine
+
H
3
N C COO
H
(CH
2
)
3
NH
3
+
Ornithine
H
2
O
Urea
Arginase
+
H
3
N C COO
H
(CH
2
)
2
CHO
N
H
COO
Proline
aKG Glu
Ornithine--
Aminotransf erase
Glutamate-5-
Semialdehyde
N
H
2
COO
Pyrroline-5-
Carboxylate
Spontaneous
1/2 O
2
H
2
O
Proline
Oxidase
NAD(P)
+
+ H
2
O
NAD(P)H + H
+
+
H
3
N C COO
H
(CH
2
)
2
COO
Glutamate
Glutamate
Semialdehyde
Dehydrogenase
H
2
O
Histidine
H
2
C COO
H
2
C
N
H
N
O
4-Imidazolone-
5-Propionate
H
2
O H
+
N
H
C COO
CH
2
CH
2
COO
H
C
H
HN
N-Formiminoglutamate
Imidazolone
Propionase
THF N
5
-Formimino-THF
+
H
3
N C COO
CH
2
CH
2
COO
H
Glutamate
Glutamate Formimino
Transf erase
+
H
3
N C
H
COO
H
2
C
N
H
N
HC COO
HC
N
H
N
Histidine Urocanate
H
2
C COO
H
2
C
N
H
N
O
4-Imidazolone-
5-Propionate
NH
4
+
Histidine
Ammonia
Lyase
Urocanate
Hydratase
H
2
O
N
5
-Formimino Tetrahydrofolate
HN
N
N
NH
C
N
O
H
2
N
C
O
N
H
CH
COO
CH
2
CH
2
C
O
OH
HN H
n
5
10
Glutamate and Glutamine
+
H
3
N C COO
CH
2
CH
2
COO
H
Glutamate
+
H
3
N C COO
CH
2
CH
2
C
H
O NH
2
H
2
O NH
4
+
Glutaminase
+
H
3
N C COO
CH
2
CH
2
COO
H
O
C COO
CH
2
CH
2
COO
NAD
+
+ H
2
O NADH + NH
4
+
Glutamate Dehydrogenase
a-Ketoglutarate Glutamate