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Author: Robert Lyons, Ph.D., 2008
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M1 Renal:
Nitrogen Metabolism (and Related Topics)
• Amino Acid Metabolism (Nitrogen metabolism)
• Folate Metabolism (“One-Carbon pathways”)
• Nucleotide Metabolism
Dr. Robert Lyons
Assistant Professor, Biological Chemistry
Director, DNA Sequencing Core
Web: http://seqcore.brcf.med.umich.edu/mcb500
Fall 2008
R. Lyons
Supplementary study material on the Web:
http://seqcore.brcf.med.umich.edu/mcb500
Amino Acid met abolism
A mino acids
Folat e met abolism
Met hylene
THF
Glu, Gln,
Asp , NH3
Met
Cycle
Urea
oxaloac et at e
Pu r in e s
Uric Acid
DNA
RNA
Py r im id in e s
( energy )
f um arat e
TCA Cycle
R. Lyons
Nucleic Acid met abolism
Protein Degradation:
• Endogenous proteins degrade continuously
- Damaged
- Mis-folded
- Un-needed
• Dietary protein intake - mostly degraded
Nitrogen Balance - expresses the patient’s current
status - are they gaining or losing net Nitrogen?
Transaminases
Collect Amines
General react ion overview:
H
H
R1
C
COO
NH2
amino
acid
(-)
(-)
+
R1 C
O
R2 C COO
O
-keto
acid
(typically
alpha-ketoglutarate)
COO
(-)
+ R2 C
COO
(-)
NH2
amino
acid
(typically glutamate)
-keto
acid
Det ails of react ion mechanism:
-keto
acid
amino
acid
H
R
C
(-)
COO
NH2
+
O
CH
P OCH2
N CH3
H
pyridoxal
phosphate
R. Lyons
R
C
(-)
COO
R C
N
CH
OH
+
H+
H
H2 O
P OCH2
+
N
H
OH
CH3
P OCH2
(-)
COO
R
C
N
N
CH
HCH
OH
N CH3
H
P OCH2
+
N
H
(-)
COO
OH
CH3
(-)
R C COO
O
+
NH2
HCH
P OCH2
OH
CH3
N
H
pyridoxamine
phosphate
+
Transfer the amine back to an acceptor -keto acid
NH2
O
CH
HCH
P OCH2
OH
+
N CH3
H
pyridoxamine
phosphate
R. Lyons
+
R
C
O
(-)
COO
-keto
acid
P OCH2
H
OH
+
N CH3
H
pyridoxal
phosphate
+
R
C
COO
NH2
amino
acid
In peripheral tissues, transaminases tend to form
Glutamate when they catabolize amino acids
In other words, alpha-ketoglutarate is the preferred
acceptor, and Glutamate is the resulting amino acid:
Some amino acid + -ketoglutarate  some alpha keto acid + Glutamate
Glutamate can donate its amines to
form other amino acids as needed
A specific example - production of Aspartate in liver
(described a few slides from now):
Glutamate + oxaloacetate  -ketoglutarate + aspartate
Ge t t ing A m ine s Int o t he Liv e r
Glutamate
Dehydrogenase:
H
(-)
O2C CH2CH2C CO(-)
2
NAD(P)
O2C CH2CH2C CO(-)
2
(-)
(mito)
NH2
glutamate
NAD(P)H
Glutamine
Synthetase:
OOC
C
-ketoglutarate
(-)
(-)
OOC
CH2CH2 COO
(+)
glut amat e
R. Lyons
ammonia
H
NH3
ATP+ NH3
NH3
O
H
(- )
+
ADP+ Pi
C
O
CH2CH2C
NH3
(+ )
glut amine
NH2
.
In t he Liv e r: Pre curse rs f or Ure a Cy cle
Glut amine is hydrolyzed t o glut amat e and ammonia:
H
(-)
OOC
H
O
C
CH2CH2C
NH3
(-)
O OC
NH2
(+)
CH2CH2 C
N H3
H2O
glut amine
O
C
OH
(+)
NH3
glut amat e
Ammonia can also be formed by the glutamate dehydrogenase reaction
and several other reactions as well.
Glut amat e donat es it s amino group t o f orm aspart at e:
Glut amat e-aspartat e aminot ransferase:
H
(- )
O 2C CH2 CH2 C
H
CO(-)
2
N H2
Glutamate
.
R. Lyons
+
( -)
O 2CC H2 C
H
CO(2-)
O
oxaloacetate
(- )
O 2C CH2 CH2 C
C O(-)
2
O
-keto
glutarate
+
(- )
O 2C CH 2 C
CO(-)
2
NH2
aspartate
2ATP + HCO3 + NH3
Carbamoy l
phosphat e
O
(-)
NH2 C OPO3
1
Pi
2
2ADP + Pi
H
(-)
OOC
C
H
(+)
(-)
CH2CH2CH2NH3
OOC
NH3
O
CH2CH2 CH2NH C NH2
C
NH
(+) 3
(+)
Ornit hine
Cit rulline
Liver mitochondrion
Liver cyt oplasm
H
H
(-)
OOC
(-)
OOC
CH2CH2CH2NH(+)
3
C
NH
NH3
(+)
O
CH2CH2CH2NH C NH2
C
(+) 3
Cit rulline
Ornit hine
O
NH2 C NH2
H
O2CCH2 C CO(-)
2
NH2
aspartate
ATP
(-)
Urea
3
5
AMP + PPi
H2O
H
H
O2CCH2C CO(-)
2
NH2
C
CH2CH2CH2NH C NH(+)
2
H
(-)
OOC
(-)
C
CH2CH2CH2NH C NH2
NH2
NH3
(+)
(-)
OOC
(+)
NH3
A rginine
(+)
4
H
(-)
O2C C C CO2
H
(-)
Fumarat e
R. Lyons
A rgininosuccinat e
Carb am o y l p h o s p h at e sy n t h e t as e I
NH
ATP
O
HO
C
ATP
3
(- )
HO
O
b ic ar b on at e
R. Lyons
C
O P
HO
c ar bo ny l
ADP
ph os p ha te
O
O
O
Pi
C
P O
NH
2
ca rb a ma te
C
NH
2
ca rb a mo yl
ADP
ph os p ha te
O r n it h in e T r a n s c a r b a m o y la s e
Carb am o y l p ho s p hat e
O
N H2 C
Pi
( -)
O P O3
H
( -)
OO C
(+ )
C H C H2 C H2 N H 3
2
C
NH
(+ )
3
O r n it h in e
R. Lyons
(- )
OOC
H
O
C
C H 2C H2 C H2 N H C
NH
(+ )
3
C it r u llin e
NH
2
A r g in in o s u c c in a t e s y n t h e t a s e
H
(-)
O2CC 2C CO2(-)
H
NH2
aspartate
H
(-)
OOC
C
NH
(+) 3
H
O
CH2CH2CH2NH C NH2
(-)
OOC
(+)
CH2CH2CH2NH C NH2
NH3
Cit rulline
(+)
ATP
R. Lyons
C
H
(-)
O2CCH2C CO(-)
2
NH2
AMP + PPi
A rgininosuccinat e
A r g in in o s u c c in a t e ly a s e
H
(-)
O2CCH2C CO2
NH2
(-)
H
(-)
OOC
C
H
(-)
(+)
CH2CH2CH2NH C NH2
OOC C
NH3
(+)
(+)
Argininosuccinat e
H
(-)
O2C C C CO2
H
(-)
Fumarat e
R. Lyons
CH2CH2CH2NH C NH2
NH
NH3
(+) 2
A rginine
A r g in a s e
H
H
(-)
OOC
(-)
OOC
C
CH2CH2CH2NH C NH2
NH
NH3
(+) 2
H2 O
O
NH2 C NH2
Urea
R. Lyons
CH2CH2CH2NH(+)
3
NH
(+) 3
(+)
Arginine
C
Ornit hine
2ATP + HCO3 + NH3
Carbamoy l
phosphat e
O
(-)
NH2 C OPO3
1
Pi
2
2ADP + Pi
H
(-)
OOC
C
H
(+)
(-)
CH2CH2CH2NH3
OOC
NH3
O
CH2CH2 CH2NH C NH2
C
NH
(+) 3
(+)
Ornit hine
Cit rulline
Liver mitochondrion
Liver cyt oplasm
H
H
(-)
OOC
(-)
OOC
CH2CH2CH2NH(+)
3
C
NH
NH3
(+)
O
CH2CH2CH2NH C NH2
C
(+) 3
Cit rulline
Ornit hine
O
NH2 C NH2
H
O2CCH2 C CO(-)
2
NH2
aspartate
ATP
(-)
Urea
3
5
AMP + PPi
H2O
H
H
O2CCH2C CO(-)
2
NH2
C
CH2CH2CH2NH C NH(+)
2
H
(-)
OOC
(-)
C
CH2CH2CH2NH C NH2
NH2
NH3
(+)
(-)
OOC
(+)
NH3
A rginine
(+)
4
H
(-)
O2C C C CO2
H
(-)
Fumarat e
R. Lyons
A rgininosuccinat e
Urea Cycle Connect s t o TCA Cycle
H
(-)
O2CCH2C CO(-)
2
Ornithine
NH2
Citrulline
Aspartate
Urea
Urea Cycle
Arginine
Argininosuccinate
Oxaloacetate
Malate
H
O2C C C CO(-)
2
H
(-)
Fumarate
TCA Cycle
-Ketoglutarate
R. Lyons
Citrate
Ge t t ing A m ine s Int o t he Liv e r
Glutamate
Dehydrogenase:
H
(-)
O2C CH2CH2C CO(-)
2
NAD(P)
O2C CH2CH2C CO(-)
2
(-)
(mito)
NH2
glutamate
NAD(P)H
Glutamine
Synthetase:
OOC
C
-ketoglutarate
(-)
(-)
OOC
CH2CH2 COO
(+)
glut amat e
R. Lyons
ammonia
H
NH3
ATP+ NH3
NH3
O
H
(- )
+
ADP+ Pi
C
O
CH2CH2C
NH3
(+ )
glut amine
NH2
2ATP + HCO3 + NH3
Carbamoy l
phosphat e
O
(-)
NH2 C OPO3
1
Pi
2
2ADP + Pi
H
(-)
OOC
C
H
(+)
(-)
CH2CH2CH2NH3
OOC
NH3
O
CH2CH2 CH2NH C NH2
C
NH
(+) 3
(+)
Ornit hine
Cit rulline
Liver mitochondrion
Liver cyt oplasm
H
H
(-)
OOC
(-)
OOC
CH2CH2CH2NH(+)
3
C
NH
NH3
(+)
O
CH2CH2CH2NH C NH2
C
(+) 3
Cit rulline
Ornit hine
O
NH2 C NH2
H
O2CCH2 C CO(-)
2
NH2
aspartate
ATP
(-)
Urea
3
5
AMP + PPi
H2O
H
H
O2CCH2C CO(-)
2
NH2
C
CH2CH2CH2NH C NH(+)
2
H
(-)
OOC
(-)
C
CH2CH2CH2NH C NH2
NH2
NH3
(+)
(-)
OOC
(+)
NH3
A rginine
(+)
4
H
(-)
O2C C C CO2
H
(-)
Fumarat e
R. Lyons
A rgininosuccinat e
C P S I is S t im u la t e d b y N A G
H
O
(-)
N -a c e t y l
H
O
(-)
OOC
OOC
CH CH C
C
2
+
2
N H3
g lu t a m a t e
Co A - C
OH
O
C
CH CH C
2
2
OH
NH
s y n t h e t as e
C
C H3
( +)
O
C H3
g lu t a m a t e
N - a c e t y l g lu t a m a t e
a c e t y l Co A
( N A G)
( r e p e a t in g t h e f ig u r e f r o m p a g e 3 o f y o u r h an d o u t )
NH
ATP
O
HO
C
( -)
bi ca rb o na te
R. Lyons
HO
O
C
ATP
3
O
O P
HO
c a rb on y l
ADP
p ho s ph at e
O
O
Pi
C
P O
NH
2
c ar ba m at e
C
NH
2
c ar ba m oy l
ADP
p ho sp h at e
-Muscle
(Amines)
Glucose
Pyruvate
Glutamate
Amino acids
-ketoglutarate
Alanine
blood
transport
Alanine -ketoglutarate
Glucose
Glutamate
Pyruvate
Live r
R. Lyons
Urea
NH3
Complicating the picture: Other tissues may be involved
Muscle:
Amino acids:
Transamination
Deamination
Alanine
purine
deamination:
(+)
Glutamate
NH4
Glutamine
Intestine:
Glutamine
(+)
Alanine NH4
Glutamine
Citrulline
Kidney:
Citrulline
NH3
(+)
NH4
Arginine
Liver:
Arginine
Glutamine
(+)
NH4
Alanine
Glu
R. Lyons
Aspartate
Urea
Why is Ammonia Toxic?
Why is Ammonia Toxic?
• Possible neurotoxic effects on
glutamate levels (and also GABA)
(due to shifting equilibria of reactions
involving these compounds)
Why is Ammonia Toxic?
• Possible neurotoxic effects on
glutamate levels (and also GABA)
(due to shifting equilibria of reactions
involving these compounds)
• Possible metabolic/energetics effects:
- alpha-ketoglutarate levels
- glutamate levels
- glutamine
2ATP + HCO3 + NH3
Carbamoy l
phosphat e
O
(-)
NH2 C OPO3
1
Pi
2
2ADP + Pi
H
(-)
OOC
C
H
(+)
(-)
CH2CH2CH2NH3
OOC
NH3
O
CH2CH2 CH2NH C NH2
C
NH
(+) 3
(+)
Ornit hine
Cit rulline
Liver mitochondrion
Liver cyt oplasm
H
H
(-)
OOC
(-)
OOC
CH2CH2CH2NH(+)
3
C
NH
NH3
(+)
O
CH2CH2CH2NH C NH2
C
(+) 3
Cit rulline
Ornit hine
O
NH2 C NH2
H
O2CCH2 C CO(-)
2
NH2
aspartate
ATP
(-)
Urea
3
5
AMP + PPi
H2O
H
H
O2CCH2C CO(-)
2
NH2
C
CH2CH2CH2NH C NH(+)
2
H
(-)
OOC
(-)
C
CH2CH2CH2NH C NH2
NH2
NH3
(+)
(-)
OOC
(+)
NH3
A rginine
(+)
4
H
(-)
O2C C C CO2
H
(-)
Fumarat e
R. Lyons
A rgininosuccinat e
Inherited Defects of Urea Cycle Enzymes: Diagnosis
Defects are diagnosed based on the metabolites seen
in the blood and/or urine.
CPSD
OTCD
ASD
ALD
AD
No elevation except ammonia; diagnosed by elimination.
Elevated CP causes synthesis of Orotate
Elevated citrulline
Elevated argininosuccinate
Elevated arginine
2ATP + HCO3 + NH3
Carbamoy l
phosphat e
O
(-)
NH2 C OPO3
1
Pi
2
2ADP + Pi
H
(-)
OOC
C
H
(+)
(-)
CH2CH2CH2NH3
OOC
NH3
O
CH2CH2 CH2NH C NH2
C
NH
(+) 3
(+)
Ornit hine
Cit rulline
Liver mitochondrion
Liver cyt oplasm
H
H
(-)
OOC
(-)
OOC
CH2CH2CH2NH(+)
3
C
NH
NH3
(+)
O
CH2CH2CH2NH C NH2
C
(+) 3
Cit rulline
Ornit hine
O
NH2 C NH2
H
O2CCH2 C CO(-)
2
NH2
aspartate
ATP
(-)
Urea
3
5
AMP + PPi
H2O
H
H
O2CCH2C CO(-)
2
NH2
C
CH2CH2CH2NH C NH(+)
2
H
(-)
OOC
(-)
C
CH2CH2CH2NH C NH2
NH2
NH3
(+)
(-)
OOC
(+)
NH3
A rginine
(+)
4
H
(-)
O2C C C CO2
H
(-)
Fumarat e
R. Lyons
A rgininosuccinat e
C P S I is S t im u la t e d b y N A G
H
O
(-)
N -a c e t y l
H
O
(-)
OOC
OOC
CH CH C
C
2
+
2
N H3
g lu t a m a t e
Co A - C
OH
O
C
CH CH C
2
2
OH
NH
s y n t h e t as e
C
C H3
( +)
O
C H3
g lu t a m a t e
N - a c e t y l g lu t a m a t e
a c e t y l Co A
( N A G)
( r e p e a t in g t h e f ig u r e f r o m p a g e 3 o f y o u r h an d o u t )
NH
ATP
O
HO
C
( -)
bi ca rb o na te
R. Lyons
HO
O
C
ATP
3
O
O P
HO
c a rb on y l
ADP
p ho s ph at e
O
O
Pi
C
P O
NH
2
c ar ba m at e
C
NH
2
c ar ba m oy l
ADP
p ho sp h at e
2ATP + HCO3 + NH3
Carbamoy l
phosphat e
O
(-)
NH2 C OPO3
1
Pi
2
2ADP + Pi
H
(-)
OOC
C
H
(+)
(-)
CH2CH2CH2NH3
OOC
NH3
O
CH2CH2 CH2NH C NH2
C
NH
(+) 3
(+)
Ornit hine
Cit rulline
Liver mitochondrion
Liver cyt oplasm
H
H
(-)
OOC
(-)
OOC
CH2CH2CH2NH(+)
3
C
NH
NH3
(+)
O
CH2CH2CH2NH C NH2
C
(+) 3
Cit rulline
Ornit hine
O
NH2 C NH2
H
O2CCH2 C CO(-)
2
NH2
aspartate
ATP
(-)
Urea
3
5
AMP + PPi
H2O
H
H
O2CCH2C CO(-)
2
NH2
C
CH2CH2CH2NH C NH(+)
2
H
(-)
OOC
(-)
C
CH2CH2CH2NH C NH2
NH2
NH3
(+)
(-)
OOC
(+)
NH3
A rginine
(+)
4
H
(-)
O2C C C CO2
H
(-)
Fumarat e
R. Lyons
A rgininosuccinat e
Clinical Management of Urea Cycle Defects
• Dialysis to remove ammonia
• Provide the patient with alternative ways to excrete
nitrogenous compounds:
* Intravenous sodium benzoate or phenylacetate
* Supplemental arginine
carbamoyl phosphate
Excreted by kidney
Ornithine
O
NH2 C NH2
Citrulline
ATP
Urea
AMP+PP i
HO
2
Arginine
Aspartate
XASD
Argininosuccinate
Excreted by kidney
XALD
Dietary
Arginine
R. Lyons
• Levulose - acidifies the gut
• Low protein diet
Degrading the Amino Acid Carbon Backbone
Easily-degraded products after transamination:
H
(-)
O2C CH2C CO(-)
2
NH3
(+)
aspartate
(-)
t ransaminat ion
O2CCH2C CO(-)
2
O
oxaloacetate
H
(-)
O2C CH2CH2C CO2
NH
(+) 3
glutamate
(-)
(-)
(-)
t ransaminat ion
O2C CH2CH2C CO2
O
-ketoglutarate
t ransaminat ion
CH3 C CO(-)
2
O
pyruvate
H
(-)
CH3 C CO2
NH3
(+)
alanine
R. Lyons
We also already know how to degrade Glutamine:
glutaminase
Glutamine ----------------> glutamate + ammonia
…and by analogy, how to degrade Asparagine:
asparaginase
Asparagine ---------------> aspartate + ammonia
Amino Acids are categorized as ‘Glucogenic’
or ‘ketogenic’ or both.
Many amino acids are purely glucogenic:
Glutamate, aspartate, alanine, glutamine,
asparagine,…
Some amino acids are both gluco- and ketogenic:
Threonine, isoleucine, phenylalanine,
tyrosine, tryptophan
The only PURELY ketogenic Amino Acids:
leucine, lysine
H
(-)
OOC
C
CH2CH2CH2NH C NH2
NH2
NH3
(+)
(+)
Arginine
Urea ( via
t he urea cy cle)
H
(-)
OOC
C
CH2CH2CH2NH(+)
3
NH
Amino acids with 5-carbon
backbones tend to form
-ketoglutarate
(+) 3
Ornit hine
-ket oglut arat e
glut amat e
H
(-)
OOC
C
(-)
O
CH2CH2C
NH3
OOC
H
(+)
N
H
Proline
(+)
glut amat e - 5 - semialdehyde
(+)
NAD(P)
NA D(P)H
H
(-)
OOC
C
H
O
CH2CH2C
NH3
(-)
OOC
OH
 - ket oglut arat e
R. Lyons
O
CH2CH2C
NH3
(+)
glut amat e
C
(+)
NH3
H2O
glut amine
NH2
Degradation and Biosynthesis of Serine and Glycine
(+)
NADH
NAD
H
(-)
OOC C
Glycine
Synthase:
NH3
CO2
(+)
(+)
NH4
+
H
THF
Glycine
(-)
Serine
Hydroxymethyltransferase:
OOC
CH
N5 -N10- methylene THF
(-)
OOC
NH3
(+)
CH2OH
THF
Serine
N5 -N10- methylene THF
C
H
2
Gly cine
H 2O
Serine
Dehydratase:
(-)
OOC
CH
NH
(+)3
CH2OH
Serine
R. Lyons
NH
(+) 3
(+)
NH4
(-)
OOC
C
CH2
(+)
NH3
(-)
OOC
C
CH3
(+)
(-)
NH2
OOC
H 2O
C
CH3
O
H
H
CH3
S
CH2
CH3
(-)
CH2 C
COO
CH2
S
CH2 C
CH2
NH3
(+)
(+)
ATP +
HO
2
NH
(+) 3
O
PPi +
Pi
(-)
COO
H
H
Ad en in e
H
H OH OH
Met hionine
S-A denosyl Met hionine
Met h yl a cce pt o r
te t rah yd ro fo lat e
Bi os ynt h et ic
Me t hy lat io n
re act io n
*
se e e xam pl es
N5 me th yl
t et rah yd ro fo la te
Methionine Cycle
And Biological
Methyl Groups
Me t hyl at ed acc ep to r
H
(+)
H
HS
CH2 CH2 C
(-)
NH3
H
NH
Ad en in e
S-Adenosy l Homoc yst eine
(-)
CH2 C
COO
NH3
(+)
Serine
H
CH2 C
(-)
COO
NH
(+) 3
Cy st eine
(remainder of
homocysteine
degraded
for energy)
H
H
H OH OH
Homoc yst eine
HS
(-)
COO
(+) 3
O
(+)
HO
CH2 C
CH2
COO
H
R. Lyons
CH2
HS
Phenylalanine and Tyrosine
(Normal pat h shown in black, pat hological react ion shown in red)
Tetrahydrobiopterin + O2
Dihydrobiopterin + H2O
(+)
NH 3
CH2
CH
(-)
(-)
COO
Phenylpyruvat e
CH
(-)
COO
Tyrosine
Homogent isat e
O
R. Lyons
CH2
Enzyme:
Phenylalanine
hydroxylase
Phenylket onuria
(no phenylalanine
hydroxylase)
C
NH 3
HO
COO
Phenylalanine
CH2
(+)
Deficiency:
Alkaptonuria
“Ochronosis”
Enz yme:
homogent isat e
dioxy genase
(you don’ t need t o
know t he rest )
Branched Chain Amino Acids
Isoleucine
CH3 CH2 CH
CH
CH3
Leucine
(-)
COO
CH3CH CH 2
NH3
CH3
(+)
CH
Valine
(-)
COO
NH3
CH3 CH
(-)
COO
CH3 NH3
(+)
(+
)
-KG
-KG
CH
-KG
--- ------------ - Transaminat ion -------- -------Glu
CH3 CH2 CH
C
CH3
Glu
(-)
COO
O
CH3CHCH 2
C
CH3
O
+
(-)
COO
Glu
CH3CH
C
CH3 O
NAD,+ CoASH
NAD,+ CoASH
NAD, CoASH
(-)
COO
--- Branched-chain -ket o acid dehydrogenase - -NADH +
CO
CH3 CH2 CH
CH3
C
O
S-CoA
NADH + CO2
NADH + CO2
2
CH3CHCH 2
C
CH3
O
S-CoA
CH3CH
C
S-CoA
CH3 O
( cont inues on t o degradat ion pat h similar t o -oxidat ion of fatt y acids)
R. Lyons
Synt hesis of Bioact ive Amines
(+)
NH 3
HO
CH 2
CH
(-)
COO
NH 3
HO
CH 2
Tyrosine
hydroxy lase
Tyrosin e
HO
HO
(+)
HO
(+)
HO
CH 2CH 2NH 3
HO
R. Lyons
COO
Dih ydroxyp heny lalanin e
( L-DOPA)
OH
HO
(+)
CH CH 2NH 3
H
Dop am ine
(-)
CH
No repine phrine
HO
OH
CHCH 2 N CH 3
H
H
Ep ineph rine
Synthesis of Bioactive Amines
CH 2
N
CH
NH3
(+)
Tryp t o ph an
(-)
HO
COO
Tryptophan
hy droxylase
CH2
N
(-)
COO
NH
(+) 3
5 -hyd roxyt ryp t o ph an
PLP-de pe ndent
de cvarboxylat ion
CO2
HO
CH 2
NAD+
N
Sero t o nin
R. Lyons
CH
CH2
NH3
(+)
Synthesis of Bioactive Amines
(-)
(-)
COO CH 2 CH2 CH COO
NH3
(+)
Glut amat e
N
N
H
CH2
NH
(+) 3
Hist idine
R. Lyons
CH
(-)
Glutam ate
de carboxylase
( PLP-depe ndent )
NH3
COO CH 2 CH 2 CH2 (+)
-amin ob ut yric acid
(GABA)
N
(COO)
Hist idine
de carboxylase
( PLP-de pe ndent )
N
H
CH2
CH2
Hist amine
NH3
(+)
NON-Essential Amino Acids:
Glutamate, aspartate, alanine, glutamine, asparagine,
(proline), glycine, serine (cysteine, tyrosine)
Essential Amino Acids:
Arginine (!), phenylalanine, methionine, histidine,
Isoleucine, leucine, valine, threonine, tryptophan, lysine
Additional Source Information
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