The document provides information on a course covering nitrogen metabolism and related topics like amino acid metabolism, folate metabolism, and nucleotide metabolism. It discusses several key metabolic pathways including: 1) Transamination reactions that transfer amino groups between amino acids and alpha-ketoglutarate. 2) The urea cycle in the liver which involves ornithine, citrulline, arginine, and other intermediates to produce urea for excretion of ammonia. 3) The connection of the urea cycle to the TCA cycle through fumarate and other intermediates to allow disposal of excess nitrogen.

1. Unless otherwise noted, the content of this course material is
licensed under a Creative Commons Attribution – Share Alike 3.0
License.
Copyright 2007, Robert Lyons.
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2. 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

3. Supplementary study material on the Web:
http://seqcore.brcf.med.umich.edu/mcb500
There are also PDF’s of class
handouts with supplemental
information available in the
table of contents for this course.

4. Glu, Gln,
Asp, NH3
Amino Acid metabolism
Folate metabolism
Nucleic Acid metabolism
Methylene
THF
Met
Cycle
Purine s Py rim idine s
Uric Acid
Urea
Amino acids
DNA
RNA
(energy)
TCA Cycle
fumarat e
oxaloacetat e

5. 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?

6. Transaminases Collect Amines
General react ion overview:
C
H
R COO
NH2
amino
acid
C
H
R COO
NH
2
amino
acid
(typically glutamate)
1 2
C
R COO
O
-keto
acid
(typically
alpha-ketoglutarate)
(
-
)
+ +
2
C
R COO
O
-keto
acid
(
-
)
1
(
-
) (
-
)
Det ails of react ion mechanism:
C
H
R COO
NH
C
H
R COO
N
N
CH
O
CH
CH
OH
O
P
pyridoxal
phosphate
amino
acid
+
H O
2
3
2
CH
CH
CH
OH
O
P
3
2
2
C
H
R COO
N
CH
CH
CH
OH
O
P
3
2
+
H
+
+
C
H
R COO
N
CH
CH
CH
OH
O
P
3
2
+
C
R COO
NH
CH
O
CH
CH
OH
O
P
pyridoxamine
phosphate
+
3
2
2
+
H
-keto
acid
(
-
)
(
-
) (
-
) (
-
)
(
-
)
N
H
N
H
N
H N
H

7. NH
N
CH
CH
CH
OH
O
P
pyridoxamine
phosphate
H
H
+ C
R COO
O
-keto
acid
N
CH
O
CH
CH
OH
O
P
pyridoxal
phosphate
H
+ C
H
R COO
NH
amino
acid
Transfer the amine back to an acceptor -keto acid

8. Some amino acid + -ketoglutarate  some alpha keto acid + Glutamate
In other words, alpha-ketoglutarate is the preferred
acceptor, and Glutamate is the resulting amino acid:
In peripheral tissues, transaminases tend to form
Glutamate when they catabolize amino acids

9. Glutamate can donate its amines to
form other amino acids as needed
Glutamate + oxaloacetate  -ketoglutarate + aspartate
A specific example - production of Aspartate in liver
(described a few slides from now):

10. Ge t t ing Amines Int o t he Live r
OCCHCH C
H
NH
CO
glutamat
e
NAD(P)
NAD(P)H
OCCHCH C CO
-k
etogluta
rate
+ NH
am
monia
O
(mito)
C
H
OOC CH
NH
CH COO
glutamate glutamine
C
H
OOC CH
NH
CHC
O
NH
NH
ATP ADP P
Glutamate
Dehydrogenase:
Glutamine
Synthetase:

11. In t he Liver: Pre cursers for Urea Cycle
Glut amine is hydrolyzed t o glut amat e and ammonia:
C
H
OOC CH
NH
CHC
glutamate
O
OH
glutamine
C
H
OOC CH
NH
CHC
O
NH
HO
NH3
Glut amat e donat es it s amino group t o f orm aspart at e:
Gluta
mate aspa
rtate
oxal
oaceta
te
+ +
-keto
g
lutara
te
OCCHCH C
H
NH
CO OCCHC
H
CO OCCHCHC
O
CO OCCH C
H
NH
CO
O
Glut amat e-aspartat e aminot ransferase:
.
.
Ammonia can also be formed by the glutamate dehydrogenase reaction
and several other reactions as well.

12. Liver mitochondrion
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH3
(
+
)
Ornit hine
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH3
(
+
)
Ornit hine
C
H
OOC CH
2
NH
3
(
+
)
(
-
) CH2
CH2
NH C
(
+
)
Arginine
C
H
OOC CH2
NH3
(
+
)
(
-
) CH
2CH
2
NH C
O
Cit rulline
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH C
O
Cit rulline
2ATP + HCO +
3
NH2C
O
3
OPO(
-
)
Carbamoyl
phosphat e
Pi
2ADP + Pi
O CCH C
H
2 2 2
aspartate
(
-
) (
-
)
CO
i
ATP
AMP + PP
C
H
OOC CH
2
NH
3
(
+
)
(
-
)
CH2
CH2
NH C
O CCH C
H
2 2 2
(
-
) (
-
)
CO
(
+
)
Argininosuccinat e
Liver cyt oplasm
O C C C
H
2 2
(
-
) (
-
)
CO
H
Fumarat e
H O
2
C
O
Urea
NH2
NH2
NH2
NH3
NH2
NH2
NH2
NH2
NH2
NH2
1
5
4
3
2

13. Ca r b a m o y l p h o s p h a t e sy n t h e t a s e I
HO C
O
O
ATP
ADP
P
NH
P
HO C
O
O
bicarbonate carbonyl
phosphate i
HO C
O
NH
carbamate
ATP
ADP
O C
O
NH
P
carbamoyl
phosphate

14. O r n it h in e T r a n s c a r b am o y las e
C
H
OOC CH
NH
CH CHNH
O r n it h in e
C
H
OOC CH
NH
CH CHNH NH
C
O
C it r ullin e
NH C
O
OPO
C ar b am o y l p ho s p hat e
P
CHNH

15. A r g in in o su c c in a t e s y n t h e t as e
O CC
H
C
H
NH
2
2 2 2
aspartate
(
-
) (
-
)
CO
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH 2
NH
C
O
Cit rulline
i
ATP AMP + PP
C
H
OOC CH
2
NH
3
(
+
)
(
-
)
CH2
CH2
NH C NH
O CCH C
H
NH
2
2 2 2
(
-
) (
-
)
CO
2
(
+
)
Argininosuccinat e

16. A r g in in o s u c c in a t e ly a se
C
H
OOC CH
2
NH
3
(
+
)
(
-
)
CH2
CH2
NH NH2
C
NH2
(
+
)
Arginine
C
H
OOC CH
2
NH
3
(
+
)
(
-
)
CH2
CH2
NH C NH
O CCH C
H
NH
2
2 2 2
(
-
) (
-
)
CO
2
(
+
)
Argininosuccinate
O C C C
H
2 2
(
-
) (
-
)
CO
H
Fumarate

17. A r g in as e
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH3
(
+
)
Ornit hine
C
H
OOC CH
2
NH
3
(
+
)
(
-
)
CH2
CH2
NH NH2
C
NH2
(
+
)
Arginine
NH2C
O
NH2
Urea
H2
O

18. Liver mitochondrion
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH3
(
+
)
Ornit hine
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH3
(
+
)
Ornit hine
C
H
OOC CH
2
NH
3
(
+
)
(
-
) CH2
CH2
NH C
(
+
)
Arginine
C
H
OOC CH2
NH3
(
+
)
(
-
) CH
2CH
2
NH C
O
Cit rulline
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH C
O
Cit rulline
2ATP + HCO +
3
NH2C
O
3
OPO(
-
)
Carbamoyl
phosphat e
Pi
2ADP + Pi
O CCH C
H
2 2 2
aspartate
(
-
) (
-
)
CO
i
ATP
AMP + PP
C
H
OOC CH
2
NH
3
(
+
)
(
-
)
CH2
CH2
NH C
O CCH C
H
2 2 2
(
-
) (
-
)
CO
(
+
)
Argininosuccinat e
Liver cyt oplasm
O C C C
H
2 2
(
-
) (
-
)
CO
H
Fumarat e
H O
2
C
O
Urea
NH2
NH2
NH2
NH3
NH2
NH2
NH2
NH2
NH2
NH2
1
5
4
3
2

19. Urea Cycle Connect s t o TCA Cycle
Arginine
Citrulline
O CCH C
H
NH
2
2 2 2
Aspartate
(
-
) (
-
)
CO
Argininosuccinate
OC C C
H
2 2
(
-
) (
-
)
CO
H
Fumarate
Malate
Oxaloacetate
TCA Cycle
-Ketoglutarate
Citrate
Urea
Ornithine
Urea Cycle

20. Ge t t ing Amines Int o t he Live r
OCCHCH C
H
NH
CO
glutamat
e
NAD(P)
NAD(P)H
OCCHCH C CO
-k
etogluta
rate
+ NH
am
monia
O
(mito)
C
H
OOC CH
NH
CH COO
glutamate glutamine
C
H
OOC CH
NH
CHC
O
NH
NH
ATP ADP P
Glutamate
Dehydrogenase:
Glutamine
Synthetase:

21. Liver mitochondrion
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH3
(
+
)
Ornit hine
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH3
(
+
)
Ornit hine
C
H
OOC CH
2
NH
3
(
+
)
(
-
) CH2
CH2
NH C
(
+
)
Arginine
C
H
OOC CH2
NH3
(
+
)
(
-
) CH
2CH
2
NH C
O
Cit rulline
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH C
O
Cit rulline
2ATP + HCO +
3
NH2C
O
3
OPO(
-
)
Carbamoyl
phosphat e
Pi
2ADP + Pi
O CCH C
H
2 2 2
aspartate
(
-
) (
-
)
CO
i
ATP
AMP + PP
C
H
OOC CH
2
NH
3
(
+
)
(
-
)
CH2
CH2
NH C
O CCH C
H
2 2 2
(
-
) (
-
)
CO
(
+
)
Argininosuccinat e
Liver cyt oplasm
O C C C
H
2 2
(
-
) (
-
)
CO
H
Fumarat e
H O
2
C
O
Urea
NH2
NH2
NH2
NH3
NH2
NH2
NH2
NH2
NH2
NH2
1
5
4
3
2

22. CPS I is St im u la t e d b y N A G
HO C
O
O
ATP
ADP
P
NH
P
HO C
O
O
bicarbonate
carbonyl
phosphate i
HO C
O
NH
carbamate
ATP
ADP
O C
O
NH
P
carbamoyl
phosphate
g lu t am at e
C
H
OOC CH
NH
CH C
O
OH
+ Co A -
C
H
OOC CH
NH
CH C
O
OH
C O
CH
C O
CH
a c et y l Co A
N - ac et y l g lu t am a t e
( N A G)
N -a c e t y l
g lu t a m a t e
s y n t h e t as e
( 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 )

23. Muscle
Liver
Glucose Pyruvate
Alanine
Amino acids
(Amines)
-ketoglutarate
Glutamate
Alanine
Pyruvate
Glucose
blood
transport
-ketoglutarate
Glutamate N
H
Urea
--

24. Arginine
Amino acids:
Alanine Glutamate
Glutamine
Transamination Deamination
purine
deamination:
NH4
(+)
Glutamine
Alanine NH4
(+)
Citrulline
NH4
(+)
Urea
Muscle:
Liver:
Intestine:
Alanine
Aspartate
Glu
Glutamine
NH3
Kidney:
Arginine
Citrulline
Glutamine
NH4
(+)
Complicating the picture: Other tissues may be involved

25. Why is Ammonia Toxic?

26. Why is Ammonia Toxic?
• Possible neurotoxic effects on
glutamate levels (and also GABA)
(due to shifting equilibria of reactions
involving these compounds)

27. 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

28. Liver mitochondrion
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH3
(
+
)
Ornit hine
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH3
(
+
)
Ornit hine
C
H
OOC CH
2
NH
3
(
+
)
(
-
) CH2
CH2
NH C
(
+
)
Arginine
C
H
OOC CH2
NH3
(
+
)
(
-
) CH
2CH
2
NH C
O
Cit rulline
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH C
O
Cit rulline
2ATP + HCO +
3
NH2C
O
3
OPO(
-
)
Carbamoyl
phosphat e
Pi
2ADP + Pi
O CCH C
H
2 2 2
aspartate
(
-
) (
-
)
CO
i
ATP
AMP + PP
C
H
OOC CH
2
NH
3
(
+
)
(
-
)
CH2
CH2
NH C
O CCH C
H
2 2 2
(
-
) (
-
)
CO
(
+
)
Argininosuccinat e
Liver cyt oplasm
O C C C
H
2 2
(
-
) (
-
)
CO
H
Fumarat e
H O
2
C
O
Urea
NH2
NH2
NH2
NH3
NH2
NH2
NH2
NH2
NH2
NH2
1
5
4
3
2

29. 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
Inherited Defects of Urea Cycle Enzymes: Diagnosis

30. Liver mitochondrion
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH3
(
+
)
Ornit hine
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH3
(
+
)
Ornit hine
C
H
OOC CH
2
NH
3
(
+
)
(
-
) CH2
CH2
NH C
(
+
)
Arginine
C
H
OOC CH2
NH3
(
+
)
(
-
) CH
2CH
2
NH C
O
Cit rulline
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH C
O
Cit rulline
2ATP + HCO +
3
NH2C
O
3
OPO(
-
)
Carbamoyl
phosphat e
Pi
2ADP + Pi
O CCH C
H
2 2 2
aspartate
(
-
) (
-
)
CO
i
ATP
AMP + PP
C
H
OOC CH
2
NH
3
(
+
)
(
-
)
CH2
CH2
NH C
O CCH C
H
2 2 2
(
-
) (
-
)
CO
(
+
)
Argininosuccinat e
Liver cyt oplasm
O C C C
H
2 2
(
-
) (
-
)
CO
H
Fumarat e
H O
2
C
O
Urea
NH2
NH2
NH2
NH3
NH2
NH2
NH2
NH2
NH2
NH2
1
5
4
3
2

31. CPS I is St im u la t e d b y N A G
HO C
O
O
ATP
ADP
P
NH
P
HO C
O
O
bicarbonate
carbonyl
phosphate i
HO C
O
NH
carbamate
ATP
ADP
O C
O
NH
P
carbamoyl
phosphate
g lu t am at e
C
H
OOC CH
NH
CH C
O
OH
+ Co A -
C
H
OOC CH
NH
CH C
O
OH
C O
CH
C O
CH
a c et y l Co A
N - ac et y l g lu t am a t e
( N A G)
N -a c e t y l
g lu t a m a t e
s y n t h e t as e
( 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 )

32. Liver mitochondrion
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH3
(
+
)
Ornit hine
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH3
(
+
)
Ornit hine
C
H
OOC CH
2
NH
3
(
+
)
(
-
) CH2
CH2
NH C
(
+
)
Arginine
C
H
OOC CH2
NH3
(
+
)
(
-
) CH
2CH
2
NH C
O
Cit rulline
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH
2
NH C
O
Cit rulline
2ATP + HCO +
3
NH2C
O
3
OPO(
-
)
Carbamoyl
phosphat e
Pi
2ADP + Pi
O CCH C
H
2 2 2
aspartate
(
-
) (
-
)
CO
i
ATP
AMP + PP
C
H
OOC CH
2
NH
3
(
+
)
(
-
)
CH2
CH2
NH C
O CCH C
H
2 2 2
(
-
) (
-
)
CO
(
+
)
Argininosuccinat e
Liver cyt oplasm
O C C C
H
2 2
(
-
) (
-
)
CO
H
Fumarat e
H O
2
C
O
Urea
NH2
NH2
NH2
NH3
NH2
NH2
NH2
NH2
NH2
NH2
1
5
4
3
2

33. Clinical Management of Urea Cycle Defects
• Dialysis to remove ammonia
• Provide the patient with alternative ways to excrete
nitrogenous compounds:
• Levulose - acidifies the gut
• Low protein diet
* Intravenous sodium benzoate or phenylacetate
* Supplemental arginine
O
rnithine
A
rgin
in
e
C
itrulline
i
A
T
P
A
M
P+P
P
A
rgin
inosuccinate
HO
2
C
O
U
rea
N
H
2
N
H
2 A
spa
rta
te
Excreted by kidney
Excreted by kidney
X
D
ieta
ry
A
rg
in
in
e
carbam
oyl phosphate
XASD
ALD

34. Degrading the Amino Acid Carbon Backbone

35. Easily-degraded products after transamination:
O CCH C
H
NH3
2 2 2
aspartate
(
-
)
CO
transamination
O CCH C
O
2 2 2
(
-
)
CO
oxaloacetate
(
-
) (
-
)
(
+
)
O C CH C
H
NH
3
2 2 2
glutamate
(
-
)
transamination
CH C
O
2 2
(
-
)
-ketoglutarate
CH2 O C
2 CH2
CO CO
(
-
) (
-
)
(
+
)
CH C
H
NH
3
3 2
alanine
(
-
)
CO
transamination
CH C
O
3 2
(
-
)
CO
pyruvate
(
+
)
We also already know how to degrade Glutamine:
Glutamine ----------------> glutamate + ammonia
Asparagine ---------------> aspartate + ammonia
…and by analogy, how to degrade Asparagine:
glutaminase
asparaginase
glutaminase

36. Many amino acids are purely glucogenic:
Glutamate, aspartate, alanine, glutamine,
asparagine,…
Some amino acids are both gluco- and ketogenic:
Threonine, isoleucine, phenylalanine,
tyrosine, tryptophan
Amino Acids are categorized as ‘Glucogenic’
or ‘ketogenic’ or both.
The only PURELY ketogenic Amino Acids:
leucine, lysine

37. C
H
OOC CH
2
NH
3
(
+
)
(
-
)
CH2
CH2
NH NH2
C
NH2
(
+
)
Arginine
Urea (via
t he urea cycle)
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
CH2
NH3
(
+
)
Ornit hine
-ket oglut arat e
glutamat e
C
H
OOC CH2
NH3
(
+
)
(
-
)
CH
2
C
glut amat e - 5 - semialdehyde
O
H
NAD(P)
NAD(P)H
(
+
)
C
H
OOC CH
2
NH
3
(
+
)
(
-
)
CH2
C
glut amate
O
OH
 - ketoglutarate
N
H
(
+
)
OOC
(
-
)
Proline
glutamine
C
H
OOC CH
2
NH
3
(
+
)
(
-
)
CH2
C
O
NH
2
H O
2
NH
3
Amino acids with 5-carbon
backbones tend to form
-ketoglutarate

38. C
H
OOC NH3
(
+
)
(
-
)
H
Glycine
NAD NADH
(
+
)
THF N -N - methylene THF
5 1
0
+
CO NH
4
(
+
)
2
C
H
OOC NH
3
(
+
)
(
-
)
2
Glycine
THF N -N - methylene THF
5 1
0
Serine
CH
OOC NH
3
(
+
)
(
-
)
CH OH
2
Glycine
Synthase:
Serine
Hydroxymethyl-
transferase:
Serine
CH
OOC NH3
(
+
)
(
-
)
CH OH
2
H O
2
C
OOC NH3
(
+
)
(
-
)
CH2
C
OOC NH
2
(
+
)
(
-
)
CH
3
C
OOC
(
-
)
CH
3
H O
2
NH4
(
+
)
O
Serine
Dehydratase:
Degradation and Biosynthesis of Serine and Glycine

39. C
H
C
OO
C
H
N
H
C
H
Methionine
Serine
C
H
C
OO
C
H
N
H
HO
S
C
H
C
H
C
OO
C
H
N
H
C
H
S-Adenosyl Met hionine
S
C
H
ATP +
H O
PPi +
Pi
C
H
O
H
H H H
OH OH
Adenine
C
H
CO
O
CH
NH
CH
Homocysteine
HS
C
H
C
OO
C
H
N
H
C
H
S-Adenosyl Homocyst eine
H
S
C
H
O
H
H H H
OH OH
Adenine
Bios ynt het ic
Met hy lat ion
react ion
Met hyl accept or
Met hylat ed acc eptor
* see exam ples
C
H
CO
O
CH
NH
Cyst eine
H
S
(remainder of
homocysteine
degraded
for energy)
tet rahydrofolat e
N5 methyl
t et rahydrofolate
Methionine Cycle
And Biological
Methyl Groups

40. Phenylalanine and Tyrosine
CH2 CH COO
NH3
(+)
(-)
Phenylalanine
Tetrahydrobiopterin + O2
Dihydrobiopterin + H2O
CH2 CH COO
NH3
(+)
(-)
Tyrosine
HO
Homogent isat e
Enzyme:
Phenylalanine
hydroxylase
Enzyme:
homogent isat e
dioxygenase
CH2 C COO
(-)
Phenylpyruvat e
O
Phenylketonuria
(no phenylalanine
hydroxylase)
(Normal path shown in black, pathological reaction shown in red)
(you don’t need to
know the rest)
Deficiency:
Alkaptonuria
“Ochronosis”

41. Branched Chain Amino Acids
Isoleucine Leucine Valine
CH COO
(
-)
NH3
(+
)
CH
CH2
CH3
CH3
CH COO
(
-
)
NH3
(
+)
CH
CH 2
CH3
CH3
CH COO
(-
)
NH3
(+
)
CH
CH3
CH3
C COO
(
-)
O
CH
CH2
CH3
CH3
C COO
(-
)
CH
CH 2
CH3
CH3
C COO
(
-
)
CH
CH3
CH3
O O
C
O
CH
CH2
CH3
CH3
C
CH
CH 2
CH3
CH3
C S-CoA
CH
CH3
CH3
O O
NAD, CoASH
+
NADH +
CO
2
NAD, CoASH
+ NAD, CoASH
+
NADH + CO
2 NADH + CO2
S-CoA
S-CoA
-KG -KG -KG
Glu Glu Glu
---------------- Transamination ----------------
--- Branched-chain -keto acid dehydrogenase ---
(continues on to degradation path similar to -oxidation of fatty acids)

42. Synthesis of Bioact ive Amines
CH 2 CH COO
NH 3
(+)
(-)
Tyrosine
HO CH 2 CH COO
NH 3
(+)
(-)
HO
HO
Dihydroxypheny lalanine
Tyrosine
hydroxylase
( L-DOPA)
HO
HO
CH 2CH NH 3
(+)
2
Dopam ine
CH CH NH 3
(+)
2
Norepinephrine
OH
H
HO
HO
CH CH N
H
2
Epinephrine
OH
H
HO
HO
CH 3

43. N
CH 2 CH COO
NH3
(+)
(-) HO
N
CH2 CH COO
NH3
(+)
(-)
Tryptophan 5-hydroxytryptophan
Tryptophan
hydroxylase
CO2
HO
N
CH 2 CH NH3
(+)
Serotonin
2
PLP-dependent
decvarboxylat ion
NAD+
Synthesis of Bioactive Amines

44. CH2 CH COO
NH3
(+)
(-)
CH 2
COO
(-)
Glut amate
Glutamate
decarboxylase
( PLP-dependent )
CH 2 CH NH3
(+)
CH 2
COO
(-)
-aminobut yric acid
(GABA)
2
N
N
H
CH2 CH COO
NH3
(+)
(-
)
Hist idine
Hist idine
decarboxylase
( PLP-dependent )
N
N
H
CH2 CH NH3
(+)
Hist amine
2
Synthesis of Bioactive Amines

45. Glutamate, aspartate, alanine, glutamine, asparagine,
(proline), glycine, serine (cysteine, tyrosine)
NON-Essential Amino Acids:
Essential Amino Acids:
Arginine (!), phenylalanine, methionine, histidine,
Isoleucine, leucine, valine, threonine, tryptophan, lysine