3glucose-6-p 3ru5p f6p + e4p + r5p 2 pep + e4p + r5p 3pg serine tryptophan + pyruvate + gap + co 2...
TRANSCRIPT
3Glucose-6-P
3Ru5P
F6P + E4P + R5P
2 PEP + E4P + R5P
3PG
Serine
Tryptophan + pyruvate + GAP + CO2
Gln
NH3 +
+
+
Aldolase
H
OH
O COO-
H
O
OH
OH
CH2OPO32-
CH2
HO
OH
OH
CH2OPO32-
H
O COO-
P
O
-O
-O
B
2-keto-3-deoxy-arabinoheptulosonate-7-phosphate synthase
CH2
HO
OH
OH
CH2OPO32-
H
O COO-
O
O
COO-
OH
OH
2-O3PO
HB
HNAD+
O COO-
OH
OH
2-O3PO
O
B
H
O COO-
OH
OHO
H-
H+O COO-
OH
OHHO
O COO-
O
OHHO
H
B
O COO-
O
OH
CH2-
HO
H+
COO-
OH
OH
O
HO
chorismatesynthase
COO-
2-O3PO
OH
O R
N
N
NH
N O
O
H
H
R B
COO-
OH
O R
N
N
NH
N O
OH
R
COO-
OH
O R
N
N
NH
N O
OH
R
H
H
COO-
OH
O R
NH
N
NH
N O
O
R H+
H
B
COO-
OH
O COO-
Chorismate
-OOC
O
COO-
OH
Prephenate
PhenylalanineTyrosine
COO-
OH
p-hydroxybenzoate
Coenzyme Q
MeO
MeO
O
O
Me
R
COO-
NH2
p-aminobenzoate
Tetrahydrofolate
COO-
NH2
Anthranilate
Tryptophan
Nictotinamide
COO-
OH
O COO-
NH2
O
RE
S
H
B H+
S
O
E
R
OH-
H+NH3
-O
O
R
H
NH2
B
H+
COO-
O COO-
NH2
H
B
H+
COO-
NH2
Pyruvate
+
Ribose-5-phosphate
Cost = 2 ATP
N
OH OH
O
COO-
2-O3PO H
B
H+
N
OH OH
OH
COO-
2-O3PO
H
HN
OH OH
OH
COO-
2-O3PO
NH
OO-
HO
OH
H
OH
H
CH2OPO32-
H
H+
NH+
O O-OH
CH2OPO32-
OH
H
OH
H
NH
HO CH2OPO32-
OH
H
OH
H
H
B
H+
NH
CH2OPO32-
OH
H
OH
H
N
CH2OPO32-
OH
H
OH
H
H
B
H+
N
CH2OPO32-
OH
H
O
H
H
B
H+
NH
O H
OH
CH2OPO32-
3 glucose + 5NADP+ + 2NAD+ + 2ATP serine + glutamine --->Tryptophan + 5NADPH + 2NADH + 2ADP + 2Pi + GAP + pyruvate + 4CO2 +
glutamate
GAP + glutamate + ATP + 2NADH = serine
glutamine costs NADPH + 2NH4+ + 2ATP
3 glucose + 4NADP+ + 2NH4+ + 4NAD+ + ADP + Pi --->
Tryptophan + 4NADPH + 4NADH + ATP + pyruvate + 4CO2
COO-
OH
O C
CH2
COO-
OH
-OOC H2C C
O
COO-
Chorismate mutase
C
O
COO-
OH
C
O
COO-
O
O
-O-OOC
O
COO-
OHO
-O
H+
O
COO-
OH
H+
O
COO-
prephenate
3 glucose + 2NAD+ + 4NADP+ + NH4+ + ATP --->
phenylalanine + R5P + 4NADPH + 2NADH + 4CO2 + ADP + Pi
3 glucose + 3NAD+ + 4NADP+ + NH4+ + ATP --->
tyrosine + R5P + 4NADPH + 3NADH + 4CO2 + ADP + Pi
In animals tyrosine is made from phenylalanine by phenylalanine hydroxylase
Tyrosine production from phenylalanine
N
N
NH
HN
O
H2N
R
Fe2+
OO
HB
N
N
NH
HN
O
H2N
R
Fe2+
-OO H
A
N
N
NH
HN
O
H2N
R
Fe4+
O2-
OH
N
N
N
HN
O
H2N
R
OH
H
A H
BH
A
HN
N
N
HN
O
HN
R
N
C
O
NH2
R
H H
AH
HN
N
NH
HN
O
H2N
R
N+
C
O
NH2
R
H C
COO-
NH3+
CH2
Fe4+
O2-
H C
COO-
NH3+
CH2 Fe2+
O
H A
H C
COO-
NH3+
CH2
C+ H
OH
H C
COO-
NH3+
CH2 C+
OH
H C
COO-
NH3+
CH2 C
OH+
H
HB
H C
COO-
NH3+
CH2 OH
Tryptophan: indolamine-2,3-dioxygenase
H C
COO-
NH3+
CH2
NH
N
Fe2+
N
N N
O2
H C
COO-
NH3+
CH2
N
N
Fe2+
N
N N
O
O
H C
COO-
NH3+
CH2
N
H C
COO-
NH3+
CH2
N
N
Fe2+
N
N N
H
H
N
Fe2+
N
N N
O
O H
O
OH C
COO-
NH3+
CH2
N
HO
O
N-formylkynurenine
N
Fe3+
N
N N
O
O-
H C
COO-
NH3+
CH2
N
H
H C
COO-
NH3+
CH2
N
HO
O
N-formylkynurenine
AmideHydrolysis
H C
COO-
NH3+
CH2
H2NO
C
O
H O-
Formate
N-formylkynurenine formamidase
Kynurenine
CO
H
O-
Formate
-O P
O
O-
O ADP
C
O
H O P
O
O-
O-
ADP
C
O
H
OP
O
-OO-
NH
HN
N R
B
H
NH
HN
N R
C
O
H
N10-formyl-THF
Loss of ATP!
N10-formyl-THF synthetase
Kynurenine-3-hydroxylase (monooxygenase)
NH
N
NH
N-
R
O
O
NH
N
NH
N-
R
O
O
O
O
NH
N
NH
N-
R
O
O
O
O
H+
NH
N
NH
N
R
O
O
O
OH
NH2
C
O
CH2 C
NH3+
H
COO-
N
N
NH
N
R
O
OHO
O
H
HA
+HCNH2
C
O
CH2 C
NH3+
H
COO-
N
N
NH
N
R
O
OHHO
HO H
B
NH2
C
O
CH2 C
NH3+
H
COO-
OH
C- NH2+
C
O
CH2 C
NH3+
H
COO-
H NH2+
C
O
CH2 C
NH3+
H
COO-
HO H
Kynurenine
3-hydroxykynurenine
N
N
NH
N
R
O
OHHO
B
H
A
N
N
NH
N
R
O
O
FAD
Lose 1 NADPH!
NH2
C
O
CH2 C
COO-
NH3+
H
OH
NH+
CH O
O-
2-O3PO
Schiff BaseFormation
NH2
C
O
CH2 C
COO-
NH+
H
OH
NH+
CH
O-
2-O3PO
B NH2
C
O
CH2 C
COO-
NH+
OH
NH
CH
O-
2-O3PO
Kynureninase
NH2
C
O
CH2 C
COO-
NH+
OH
NH
CH
O-
2-O3PO
NH2
C
O
H2C C
COO-
NH
OH
NH
HC
O-
2-O3PO
O-
3-hydroxy-anthranilate-OH
AH
H3C C
COO-
NH+
NH
HC
O-
2-O3PO
H A H C
COO-
NH+
NH+
HC
O-
2-O3PO
CH3
+
Schiff BaseHydrolysis
H C
COO-
NH3+
CH3
NH+
C
O-
2-O3PO
OH
Alanine
So…Trp = alanine - ATP - NADPH + 3-hydroxyanthranilate
If: Ala = 13 ATP
Then: Trp = 12 ATP - NADPH + 3-hydroxyanthranilate
His
Fe2+
HisO
OH2OH2
O HO
H2N
COO-
O2
O O
His
Fe2+
His
O-O
HO
NH2
COO-
O- O
His
Fe3+
His
O-O
HO
NH2
COO-
O- O
His
Fe2+
His
O-O
HO
NH2
+
COO-
O- O
His
Fe2+
His
O-O
O
NH2
+
COO-
HB
O- O
His
Fe2+
His
O-O
O
NH2
+
COO-
His
Fe2+
His
O-O
OO
-OOC
NH2
O-H
H+H
B
2-amino-3-carboxymuconate-6-semialdehyde
3-hydroxyanthranilate dioxygenase
OO
-OOC
NH
-OH
HA
NH
COO-
COO-
HO
HH
BH
A
N
COO-
COO-
If you need nictotinamide it ends here
OO
-OOC
H2N
-OH
N
COO-
COO-
Non-enzymatic
NH+
C
O
NH2
2-amino-3-carboxymuconatesemialdehyde dehydrogenase
Mechanism and cofactorcompletely unknown
NAD+
-OOCO NH2
-OOCO NH2
COO-
=
Further degradation
Assume loss of NADH
-OOCO NH2 HC
O
C
O
O-
NH2
N+
C
O
H
SH
E
B
HC
O-
C
O
O-
NH2
S
E
C
O
C
O
O-
NH2
S
E
N
C
O
H
R
-O
H
B
C
O
C
O
O-
NH2
-O
H
A
2-aminomuconate
NADH
NAD+
C
O
C
O O-
NH2
-O
2-aminomuconate
OH
BA
H
C
O
C
O O-
NH2
-OO
HH
BAH
-O
OO
O-O
N
CH2N
O
R
H H
HA
-O
OO
O-O
N+
CH2N
O
RNADP+ NADPH
α-ketoadipate
Trp = 12 ATP - 2 NADPH - (NADH?) + NADH + α-ketoadipate + NH3
+ NH3
CH2
CH2
C O
COO-S
C-
N+X
Y
R
S
C
N+X
Y
R
C
CH2
CH2
O-
C
O-OS
C
NX
Y
R
C
CH2
CH2
O-
CO2
SS
H A
S
C
N+X
Y
R
C
CH2
CH2
O-
HSS
S
C-
N+X
Y
R
C
CH2
CH2
O
HSS
HS
CoAB
H2C CH2 C
O
S CoA
HSS-
Glutaryl-CoA
CH2
COO-
CH2
COO-
CH2
COO-
CH2
COO-
CH2
COO-
CH2-OOC
α-ketoadipate dehydrogenase Same mechanism as pyruvate dehydrogenase and α-ketoglutarate dehydrogenase.
SS-H
N+
C
O
NH2
SS
N
C
O
NH2
α-ketoadipate = NADH + glutaryl-CoA
CH CH C
O
S CoA
Glutaryl-CoA
CH2-OOC
H
H
B
N
N
NH
N
R
O
O
HA
NH
N
NH
HN
R
O
O
FAD FADH2
C C C
O
S CoACH2-OOC
H
H
Glutaconyl-CoA
α-ketoadipate = NADH + FADH2 + glutaconyl-CoA
C C C
O
S CoACH2C
H
H
Glutaconyl-CoA
O
-O CH CH C
O-
S CoACH2
CO2
AH
C
O
S CoA
H
H
H3C
Crotonyl-CoA
C
O
S CoA
H
H
H3C
Crotonyl-CoA
HO
H
BH
A
C
O
S CoACH2
CH3
H
HO
β-hydroxybutyryl-CoA
α-ketoadipate = 2 NADH + FADH2 + Acetoacetyl-CoA
C
O
S CoACH2
CH3
H
O
β-hydroxybutyryl-CoA
H
B
N+
C
H2N
O
R
C
O
S CoACH2
O
H3C
N
C
H2N
O
R
Acetoacetyl-CoA
C
O
S CoACH2
O
H3C
Acetoacetyl-CoA
H
SCoA
B
C
O
S CoACH2
O-
H3C
SCoA
C
O-
S CoACH2
O
H3C
SCoA
AH
C
O
S CoACH3
2
α-ketoadipate = 2 NADH + FADH2 + 2 Acetyl-CoA
So…Trp = 12 ATP - 2 NADPH + NH3+ α-ketoadipate
If: α-ketoadipate = 2 NADH + FADH2 + 2 Acetyl-CoA
If: Acetyl-CoA = 3 NADH + FADH2 + GTP
Then: α-ketoadipate = 8 NADH + 3 FADH2 + 2 GTP
If GTP = ATP, NADH = 3 ATP FADH2 = 2 ATP and NH3 = -2 ATP
Then: Trp = 12 ATP + 8 NADH + 3 FADH2 + 2 GTP - 2 NADPH + NH3
Remember malate dehydrogenase + malic enzyme converts NADH + NADP+ ---> NAD+ + NADPHSo….-2 NADPH = -2 NADH
Then: Trp = 12 ATP + 6 NADH + 3 FADH2 + 2 GTP + NH3
Then: Trp = 36 ATP + N10-formyl-THF
Tyrosine and phenylalanine degradation
N
N
NH
HN
O
H2N
R
Fe2+
OO
HB
N
N
NH
HN
O
H2N
R
Fe2+
-OO H
A
N
N
NH
HN
O
H2N
R
Fe4+
O2-
OH
N
N
N
HN
O
H2N
R
OH
H
A H
BH
A
HN
N
N
HN
O
HN
R
N
C
O
NH2
R
H H
AH
HN
N
NH
HN
O
H2N
R
N+
C
O
NH2
R
H C
COO-
NH3+
CH2
Fe4+
O2-
H C
COO-
NH3+
CH2 Fe2+
O
H A
H C
COO-
NH3+
CH2
C+ H
OH
H C
COO-
NH3+
CH2 C+
OH
H C
COO-
NH3+
CH2 C
OH+
H
HB
H C
COO-
NH3+
CH2 OH
H C
COO-
NH3+
CH2 OH -OOC C
O
CH2 OH
C CH2 OH
Fe2+
O
CO- O
OO
C CH2 OH
Fe3+
O
CO- O
OO
C CH2 OH
Fe4+
O-
CO- O
O-
O
C CH2 OH
Fe4+
O-O2-
O
+ CO2
C CH2
+HC
OH
Fe2+
O-
O
O-
OH
CH2C
O
-O
O
HB
HA
OH
CH2C
O
-O
HO
OH
CH2C
O
O-
O-
Fe2+
OO
OH
CH2C
O
O-
O
Fe2+
O-O
OH
CH2C
O
O-
O
Fe3+
O2-
OH
CH2C
O
O-
O
Fe3+
O2-
O
O
OH
CH2C
O
O-
O
Fe2+O-
O
-O C
O
CH2 C
O
CH
OH
COO-
H
-O C
O
CH2 C
O
CH
OH
H
COO-
-O H
A H
-O C
O
CH2 C
O
CH2
HO
H
COO-
O
H
B
-O C
O
CH2 C
O-
CH2
HO
H
COO-
O
HA
-O C
O
CH2 C
O
CH3
Makes fumarate + acetoacetate at the expense of NADPH and ascorbate
So…Phe = fumarate + acetoacetate - NADPH - Asc + NH3 andTyr = fumarate + acetoacetate - Asc + NH3
If: fumarate = malate
Then: Phe = malate + acetoacetate - NADPH - Asc + NH3 andTyr = malate + acetoacetate - Asc + NH3
If: malate = pyruvate - NADH + NADPH
Then: Phe = pyruvate + acetoacetate - NADH - Asc + NH3 andTyr = pyruvate + acetoacetate - Asc + NH3 - NADH + NADPH
If: acetoacetate = 2 Acetyl-CoA - ATP
Then: Phe = pyruvate + 2 Acetyl-CoA - NADH - Asc + NH3 -ATP andTyr = pyruvate + 2 Acetyl-CoA - Asc + NH3 - NADH + NADPH - ATP
If: pyruvate = 4 NADH + FADH2 + GTP
If: Acetyl-CoA = 3 NADH + FADH2 + GTP
Then: Phe = 9 NADH + 3 FADH2 + 2 GTP - Asc + NH3 andTyr = NH3 + 2 GTP + 3 FADH2 + 9 NADH + NADPH - Asc
Then: Phe = 9 NADH + 3 FADH2 + 2 GTP - Asc + NH3 andTyr = NH3 + 2 GTP + 3 FADH2 + 9 NADH - NADPH - Asc
If: Asc = - NADPH
Then: Phe = 9 NADH + 3 FADH2 + 2 GTP - NADPH + NH3 andTyr = NH3 + 2 GTP + 3 FADH2 + 9 NADH - 2 NADPH
If: NADPH = NADH
Then: Phe = 8 NADH + 3 FADH2 + 2 GTP + NH3 andTyr = NH3 + 2 GTP + 3 FADH2 + 7 NADH
If GTP = ATP, NADH = 3 ATP FADH2 = 2 ATP and NH3 = -2 ATP
Then: Phe = 30 ATPTyr = 27 ATP
Histidine degradation
C C
COO-
NH3+
H
NH
NH
H
B
C CH
-OOC
H
HN
N
Histidine Urocanate
C CH
-OOC N
N
N+
C
O
NH2
R
N
C
O
NH2
R
H
B
H
AH
H2C CH
-OOC N
N
N
C
O
NH2
R
H
O
H
B
HA
H2CH2C
-OOC N
N
N
C
O
NH2
R
HO
H A
N+
C
O
NH2
R
H2CH2C
-OOC HN
N
OH
B
HA
H2C
CH2
COO-
NH
N
O
4-imidazole-5-propionate
HistidineAmmonia
lyase
Urocanase
Urocanase
UrocanaseUrocanase
Urocanase
Imidazolonepropionase
Glutamateformiminotransferase
H2C
CH2
COO-
NH
N
O
4-imidazole-5-propionate
O-
HB
H A
H2C
CH2
COO-
NH
HN
-OOC
N-formiminoglutamate
N
N
H NH
H A
H C
COO-
NH3+
CH2 CH2 COO-
N
N
CH NHHN
N5-formimino-THF
Glutamate
So….Histidine = glutamate + N5-formimino-THF
If: Glu = α-ketoglutarate + NADPH + NH3
Then: His = α-ketoglutarate + NADPH + NH3
If: α-ketoglutarate = 4 NADH + 2 GTP + 2 FADH2 + NADPH
Then: His = 4 NADH +2 GTP + 2 FADH2 + NADPH + NH3
If: NADH = 3 ATPGTP = ATP
FADH2 = 2 ATPNH3 = -2 ATP
Then: His = 16 ATP + NADPH + N5-formimino-THF
Amino acids as precursors for biological molecules
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.