oxaloacetate 3NADPH NH3 3ATP ---> threonine 3NADP 3ADP 3Pi

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oxaloacetate 3NADPH NH3 3ATP ---gt
threonine 3NADP 3ADP 3Pi
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gamma lyase/beta synthase
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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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2 ways to degrade serine. (1) Serine dehydratase
breaks the C?-C? bond
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Serine is converted to pyruvate NH3 at no cost
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So Ser pyruvate NH3
If Pyruvate 4 NADH 1 FADH2 GTP
Then Ser 4 NADH FADH2 GTP NH3
If NADH 3 ATP GTP ATP FADH2 2 ATP NH3 -2
ATP
Then Ser 13 ATP
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(2) Serine hydroxymethyltransferase bifunctional
enzyme
STEP 1 formation of glycine
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What happens to formaldehyde?
STEP 2 formation of N5,N10-methylene-THF
Serine hydroxymethyl transferase can be run in
reverse to make serine from glycine and
N5,N10-methylene THF
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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
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What happens to 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
Sodegradation of serine with serine
hydroxymethyltransferase followed by the glycine
cleavage system makes 2 N5,N10-methylene-THF, NH3
and NADH
If NADH is 3 ATP but NH3 is -2 ATP
Then Ser 1 ATP 2 N5,N10-THF
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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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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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Cysteine is degraded by 2 pathways (1) Oxidation
by cysteine dioxygenase
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SoCys pyruvate NH3
If Pyruvate 4 NADH GTP FADH2
Then Cys 4 NADH GTP FADH2 NH3
If GTP ATP NADH 3 ATP FADH2 2 ATP H3 -2
ATP
Then Cys 13 ATP
However..
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(2) Cysteine desulfurylase looks like serine
dehydratase
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Cys 1 pyruvate NH3 H2S
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Pyruvate NH3 ATP NADPH ---gt alanine ADP
Pi NADP
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Methionine
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Acetohydroxyacid isomeroreductase
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Citrate synthase
Aconitase
IDH
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Pyruvate ?-ketobutyrate 2 NADPH NH3 ATP
---gt Isoleucine 2NADP ADP Pi
2Pyruvate 2 NADPH NH3 ATP ---gt valine
2NADP ADP Pi
2Pyruvate 2 NADPH NH3 ATP Acetyl-CoA
NAD ---gt leucine 2NADP NADH ADP Pi
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Degradation of branched chain amino acids
Valine, leucine and isoleucine
First three steps are shared
Branched chain amino acid aminotransferase
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Leucine degradation
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So.Leucine 3 Acetyl-CoA NADH FADH2 NH3 -
ATP
If succinyl-CoA goes to succinate then you lose
a GTP
Then Leu 3 Acetyl-CoA NADH FADH2 NH3 - 2
ATP
If Acetyl-CoA 3 NADH FADH2 GTP
Then Leu 10 NADH 4 FADH2 3 GTP NH3 - 2
ATP
If GTP ATP, NADH 3 ATP FADH2 2 ATP and NH3
-2 ATP
Then Leu 37 ATP
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Valine degradation
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Sopropionyl-CoA succinyl-CoA - ATP
Then Valine 3 NADH FADH2 succinyl-CoA -
ATP NH3
If Succinyl-CoA malate GTP FADH2
If GTP ATP
Then Val malate 3 NADH 2 FADH2 NH3
If Malate pyruvate NADPH - NADH
Then Val 2 FADH2 pyruvate NADPH 2 NADH
NH3
If Pyruvate ---gt 4 NADH GTP FADH2
Then Val 6 NADH GTP 3 FADH2 NADPH NH3
If GTP ATP, NADH 3 ATP FADH2 2 ATP and NH3
-2 ATP
Then Val 23 ATP NADPH
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Isoleucine Degradation
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Sopropionyl-CoA succinyl-CoA - ATP
Then Isoleucine 2 NADH FADH2 Acetyl-CoA
succinyl-CoA - ATP NH3
If Succinyl-CoA malate GTP FADH2
If GTP ATP
Then Ile Acetyl-CoA malate 2 NADH 2
FADH2 NH3
If Malate pyruvate NADPH - NADH
Then Ile Acetyl-CoA 2 FADH2 pyruvate
NADPH NADH NH3
If Pyruvate ---gt 4 NADH GTP FADH2
If Acetyl-CoA ---gt 3 NADH GTP FADH2
Then Ile 8 NADH 2 GTP 4 FADH2 NADPH NH3
If GTP ATP, NADH 3 ATP FADH2 2 ATP and NH3
-2 ATP
Then Ile 32 ATP NADPH
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3Glucose-6-P
3Ru5P 6NADPH
F6P E4P R5P 6 NADPH
2 PEP ATP E4P R5P 6 NADPH
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Aldolase
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