Trp

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E4P
Trp
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Tryptophan
Tryptophan
ATP Histidine
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Remember the cost of glutamate
?KG NADPH NH3 ATP ---gt glutamate NADP
ADP Pi
Making glycine, alanine, aspartate, glutamate
costs 1 NADPH and 1 ATP
Making glutamine costs an additional ATP Making
asparagine costs an additional 2ATP
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?KG NADPH NH3 ATP ---gt glutamate NADP
ADP Pi
?KG 3NADPH NH3 2ATP ---gt proline 3NADP
2ADP 2Pi
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Proline degradation
Proline
Pyrroline-5-carboxylate
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Non-enzymatic
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Glutamate semialdehyde dehydrogenase
Glutamate semialdehyde
Glutamate
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So.Proline glutamate
If Glu ?-ketoglutarate NADPH NH3
Then Pro ?-ketoglutarate NADPH NH3
If ?-ketoglutarate 4 NADH 2 GTP 2 FADH2
NADPH
Then Pro 4 NADH 2 GTP 2 FADH2 2 NADPH
NH3
If NADH 3 ATP GTP ATP FADH2 2 ATP NH3 -2
ATP
Then Pro 16 ATP 2 NADPH
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Arginine Degradation
Arginase
Arginase
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Ornithine-?-aminotransferase
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Ornithine-?-aminotransferase
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Ornithine-?-aminotransferase
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Glutamate semialdehyde dehydrogenase
Glutamate semialdehyde
Glutamate
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?KG NADPH NH3 ATP ---gt glutamate NADP
ADP Pi
?KG Acetyl-CoA 4NADPH 3NH3 7ATP CO2
---gt arginine 4NADP 6ADP 1AMP 6Pi 1PPi
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SoArg Glutamate NADPH NH3
If Glu ?-ketoglutarate NADPH NH3
Then Arg ?-ketoglutarate 2 NADPH 2 NH3
If ?-ketoglutarate 4 NADH 2 GTP 2 FADH2
NADPH
Then Arg 4 NADH 2 GTP 2 FADH2 3 NADPH
2NH3
If NADH 3 ATP GTP ATP FADH2 2 ATP NH3 -2
ATP
Then Arg 14 ATP 3 NADPH
What is the problem with arginine degradation?
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alpha-ketoglutarate
glutamate
glutamate semialdehyde
Control point
proline
N-acetylglutamate semialdehyde
arginine
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Remember the cost of aspartate
oxaloacetate NADPH NH3 ATP ---gt aspartate
NADP ADP Pi
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oxaloacetate 4NADPH 2NH3 3ATP pyruvate
succinyl-CoA ---gt lysine 4NADP 3ADP 3Pi
CO2
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This is this is not the only way to make lysine
Homocitrate synthase
Homoaconitase
Homoisocitrate DH
Homoaconitase
?-ketoadipate
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?-KG acetyl-CoA 2NH3 2NAD 4ATP
4NADPH ---gt Lysine CO2 2NADH 4NADP 4ADP
4Pi
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NADPH
Lysine Degradation
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NAD
?-ketoadipate
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NADH
FADH2
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NADH
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SoLysine NADH ?-ketoadipate 2 NH3
If ?-ketoadipate 2 NADH FADH2 2 Acetyl-CoA
Then Lys 3 NADH FADH2 2 Acetyl-CoA 2 NH3
If Acetyl-CoA 3 NADH FADH2 GTP
Then Lys 9 NADH 3 FADH2 2 GTP 2 NH3
If GTP ATP, NADH 3 ATP FADH2 2 ATP and NH3
-2 ATP
Then Lys 35 ATP
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oxaloacetate 3NADPH NH3 3ATP ---gt
threonine 3NADP 3ADP 3Pi
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Threonine can be degraded in three ways
(1) Threonine dehydrogenase pathway
Threonine Dehydrogenase
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Must break C?-C? bond on an amino acid and
stabilize a carbanion
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2-amino-?-ketobutyrate lyase
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What happens to the glycine? Glycine Cleavage
System trifunctional enzyme
STEP1 decarboxylation of glycine
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STEP 2 formation of N5,N10-methylene-THF
THF
N5,N10-methylene-THF
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STEP 3 regeneration of catalytic site
NADH
NAD
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There is another pathway of glycine degradation
From glycine cleavage system
Combine the glycine cleavage system with a
reverse of the serine hydroxymethyltransferase rxn
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So2 glycine 1 serine NADH NH3
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If 2 Gly serine NADH NH3
If Ser pyruvate NH3
Then 2 Gly pyruvate NADH 2 NH3
If Pyruvate 4 NADH GTP FADH2
Then 2 Gly 5 NADH GTP FADH2 2 NH3
If NADH 3 ATP GTP ATP FADH2 2 ATP NH3 -2
ATP
Then 2 Gly 14 ATP, 1 Gly 7 ATP
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So Thr Gly Acetyl-CoA NADH
If glycine is degraded by glycine cleavage
system you get 1 N5,N10-methylene
tetrahydrofolate, NH3 and NADH
Then Thr N5,N10-THF NH3 2 NADH Acetyl-CoA
If Acetyl-CoA 3 NADH GTP FADH2
Then Thr N5,N10-THF NH3 5 NADH GTP
FADH2
If NADH 3 ATP GTP ATP FADH2 2 ATP NH3 -2
ATP
Then Thr N5,N10-THF 16 ATP
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If 2 Thr are degraded to 2 Gly
Then 2 Thr 2 Gly 2 NADH 2 Acetyl-CoA
If 1 Gly N5,N10- THF 1 NH3 1 NADH by
glycine cleavage system
And 1 Gly N5,N10-methylene tetrahydrofolate
serine by serine hydroxymethyltransferase
Then 2 Thr 1 NH3 3 NADH 2 Acetyl-CoA
serine
If Ser pyruvate NH3
Then 2 Thr 2 NH3 3 NADH 2 Acetyl-CoA
pyruvate
If Acetyl-CoA 3 NADH GTP FADH2 Pyruvate
4 NADH GTP FADH2
Then 2 Thr 2 NH3 13 NADH 3GTP 3 FADH2
If GTP ATP, NADH 3 ATP FADH2 2 ATP and NH3
-2 ATP
Then 2 Thr 44 ATP, Thr 22 ATP
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(2) Threonine can be degraded by serine
hydroxymethyltransferase
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What happens to acetaldehyde cant be put onto
THF
NAD
NADH
Acetaldehyde dehydrogenase
Thr glycine Acetyl-CoA NADH
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Thus Thr Gly Acetyl-CoA NADH
If glycine is degraded by glycine cleavage
system you get 1 N5,N10-methylene
tetrahydrofolate, NH3 and NADH
Then Thr N5,N10-THF NH3 2NADH Acetyl-CoA
If Acetyl-CoA 3 NADH GTP FADH2
Then Thr N5,N10-THF NH3 5 NADH GTP
FADH2
If NADH 3 ATP GTP ATP FADH2 2 ATP NH3 -2
ATP
Then Thr N5,N10-THF 16 ATP
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(3) Threonine can be converted to ?-ketobutyrate
by threonine (serine) dehydratase
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What happens to ?-ketobutyrate? ?-ketobutyrate
dehydrogenase Same mechanism as pyruvate
dehydrogenase and ?-ketoglutarate dehydrogenase.
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NAD
NADH
Thr propionyl-CoA NADH
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What happens to propionyl-CoA? Propionyl-CoA
carboxylase
Loss of ATP!
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Methylmalonyl-CoA epimerase Why?
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Stability order of radicals allylic gt R3C gt R2CH
gt RCH2 gt CH3 gt vinylic
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So Thr succinyl-CoA - ATP NADH
If Succinyl-CoA malate GTP FADH2
Then Thr malate GTP - ATP NADH FADH2
If GTP ATP
Then Thr malate NADH FADH2
If Malate pyruvate NADPH - NADH
Then Thr FADH2 pyruvate NADPH
If Pyruvate ---gt 4 NADH GTP FADH2
Then Thr 4NADH GTP 2 FADH2 NADPH
If GTP ATP, NADH 3 ATP FADH2 2 ATP and NH3
-2 ATP
Then Thr 17 ATP NADPH
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Degradation of glycine by this pathway makes 1
N5,N10-methylene tetrahydrofolate, NH3 and NADH
If NADH is 3 ATP but NH3 is -2 ATP
Then Gly 1 ATP 1 N5,N10-THF
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Asp semialdehyde
lysine
threonine/methionine
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methionine
O-succinylhomoserine
homoserine
O-phosphohomoserine
threonine
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oxaloacetate 3NADPH 2ATP succinyl-CoA
cysteine N5-methyl-THF ---gt methionine
succinate pyruvate 3NADP 2ADP 2Pi
N5-methyl-THF comes from serine ---gt glycine
N5,N10-methylene THF
N5,N10-methylene THF NADH ---gt N5-methyl THF
NAD
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3-phosphoglycerate NAD NADPH NH4 ATP
---gt Serine NADH NADP ADP 2Pi
3-phosphoglycerate NAD NADPH NH4 ATP
THF ---gt glycine NADH NADP ADP 2Pi
N5,N10-methylene THF
Reverse the glycine cleavage system
CO2 NH4 N5,N10-methylene THF NADH
---gt Glycine THF NAD