Download Amino Acid Breakdown

Amino Acid Breakdown
OH
O
O
H3N
O
H3N
O
Leucine
O
H3N
O
Valine
S
O
H3N
O
Isoleucine
H3N
O
Threonine
O
Methionine
NH3
Nutritionally Essential
NH
O
O
H3N
O
H3N
O
Phenylalanine
H3N
O
Tryptophan
O
Lysine
H2N
Conditionally Nutritionally Essential
NH2
NH
OH
N
NH
SH
O
H3N
O
O
H3N
O
Tyrosine
O
H3N
O
Cysteine
H3N
O
Arginine
O
Histidine
NH2
O
Nutritionally Non-essential
OH
O
H3N
O
H3N
O
O
H3N
O
Alanine
O
H3N
O
Serine
O
O
Glycine
O
O
Glutamate
O
H3N
O
Aspartate
H2N
O
H3N
O
O
Asparagine
O
O
H3N
O
Glutamine
N
H2
O
Proline
O
Alanine Cycle
Liver
Pyruvate
Glucose
Glucose
4 ATP + 2 GTP
Muscle
2 ATP
Alanine cycle
Protein
Pyruvate
Alanine
NH4
Alanine
α-ketoacids
Amino acids
Urea
Urea
NH4
Kidney
Excretion
Products
Branched-chain
amino acids
Glutamine
Brain
Overview of Nitrogen Flow
α-amino acid
L-amino
acid
oxidase
[FAD]
α-ketoacid
+ H2O2
α-amino acid
Glutamate
α-ketoglutarate
Aminotransferase
ADP
Glutamine + P
i
ATP synthetase
NAD(P)
Glutamate
NAD(P)H
+ α-ketoglutarate
Glutamate
dehydrogenase
α-ketoacid
Glutaminase
NH4+
N-acetylglutamate
Glutamine
H2O
Carbamoyl
phosphate
synthase I
Ornithine
α-amino acid
O
C
NH2
H2N
Urea
Fumarate
Oxaloacetate
Urea Cycle
Aminotransferase
Aspartate
α-ketoacid
Aminotransferases
O
O
O
O
O
O
O
α-Ketoglutarate
H3N
O
Aspartate
aminotransferase
O
Aspartate
O
O
+
O
O
Glutamate
O
O
Oxaloacetate
O
O
O
O
H3N
+
O
O
O
H3N
+
O
O
O
O
α-Ketoglutarate
H3N
O
Alanine
aminotransferase
O
Alanine
O
+
O
O
Glutamate
O
Pyruvate
SGOT (Serum Glutamate Oxaloacetate Transaminase) = AST (Aspartate
aminotransferase)
SGPT (Serum Glutamate Pyruvate Transaminase) = ALT (Alanine
aminotransferase)
O
Enzyme
C
O
α-amino
acid
H
H
H
N
CH
O P O
O
N
O
Enzyme
O
H
NH2
O
HO
H3C
R
H
N
H3C
O
O
α-keto
acid
C
R
CH2
O P O
O
N
H3C
N
H
O
O
HO
H3C
O P O
O
N
Loss of
α-carbon
proton
O
C
Enzyme
R
NH2 O
H
NH
O P O
R
H
Enzyme
O
H
CH
O
O
NH3
C
NH
H
O
HO
O
NH2
CH
O
NH2
Enzyme
R
NH
HO
H
Enzyme
C
O
H
NH2
CH2
Hydrolysis HO
H3C
O
H
O
HO
H3C
R
NH
CH
O
O P O
O P O
N
C
N
H
O
Glutamate Dehydrogenase
O
O
O
NAD(P) NAD(P)H
H 3N
O
O
O
H2O
NH4
O
H2N
O
Glutamate
Dehydrogenase
O
O
O
Glutamate
Glutamate + NAD
Glutamate
Dehydrogenase
O
O
α-Ketoglutarate
∆G´° = +30 kJ/mol
α-ketoglutarate + NADH
Regulators:
Inhibitors: NADH, GTP
Activators: NAD, leucine, ADP
Hyperinsulinemia/Hyperammonemia mutations
Bovine Glutamate Dehydrogenase (PDB ID 3MW9)
Bovine Glutamate Dehydrogenase (PDB ID 3MW9)
Substrate
NADH
Substrate
NADH
Glutamate
Glutamate
GTP
Regulatory
NADH
GTP
Regulatory
NADH
Overview of Amino Acid Breakdown
Alanine
* Denotes amino acids that enter the TCA
cycle in more than one place
Bold denotes gluconeogenic amino acids
Pyruvate
Italics denotes ketogenic amino acids
Bold italics denotes amino acids that are
both glucogenic and ketogenic
Isoleucine*
Leucine*
Threonine*
CO2
Acetyl-CoA
Asparagine
Cysteine
Glycine
Serine
Threonine*
Tryptophan*
Ketone
bodies
Acetoacetyl-CoA
Oxaloacetate
Aspartate
Citrate
Leucine*
Lysine
Phenylalanine*
Tryptophan*
Tyrosine*
Malate
Isoleucine*
Methionine
Valine
Threonine*
Succinate
Both
Isoleucine*
Phenylalanine*
Threonine*
Tryptophan*
Tyrosine*
cis-Aconitate
Isocitrate
Glutamine
CO2
Glutamine
synthetase
Tyrosine*
Phenylalanine*
Ketogenic
Leucine*
Lysine
CO2
Propionyl-CoA
Succinyl-CoA
α-Ketoglutarate
Histidine
NH4
Glutamate
Proline
Glutaminase
Fumarate
Glucogenic
Alanine
Arginine
Asparagine
Glutamate
Glutamine
Glycine
Histidine
Methionine
Proline
Serine
Valine
NH4
Glutamine
Ornithine
Arginine
Glutamine Metabolism
O
O
NH2
H2O
NH4
O
H3N
H3N
Glutaminase
O
O
O
Glutamine
Glutamate
O
O
ATP
O
ADP
H3N
O
Glutamine
Synthetase
O
O
O
Pi
NH4
O P O
H3 N
O
O
H3N
O
Glutamine
Synthetase
O
Glutamate
O
Acetyl-CoA
O
CoA-SH
H3N
O
CH3
O C
O
HN
O
Glutamate
O
O
Glutamine
N-Acetylglutamate
O
NH2
N-Acetylglutamate
Synthase
O
O
N-Acetylglutamate
Urea Cycle
NH2
C
O
NH2
C
NH2
O
Urea
NH3
Ornithine
+
Carbamoyl
phosphate
synthetase I
O
NH3
NH4
2 ATP
O
O P O
Ornithine
2 ADP
+ Pi
OH
O
C
O
H3N
Arginase
O
H3N
O
Pi
NH2
C
HN
NH2
O
O
Ornithine
transcarbamoylase
H2O
NH2
Arginine
C
HN
O
Citrulline
H3N
H3N
O
O
O
O
O
O
Mitochondrial
Matrix
O
Fumarate
Cytoplasm
O
Aspartate O
NH2
O
Argininosuccinase
HN
H3N
NH
HN
O
C
O
C H
N
O
O
ATP
AMP
+ PPi
O
ATP
OH
O
O
O
Argininosuccinate
H3N
O
O
C
O
Citrulline
H3N
O
O
Argininosuccinate synthetase
OH
ADP
O
C
NH4
Pi
OH
O
O P O
O
H2N
C
O
ATP
Carbamoyl
phosphate
synthetase I
ADP
NH2
O
C
O P O
O
O
Metabolism of Small Side-chain Amino Acids
(Glycine, Serine, Cysteine, and Threonine)
Glutamate α-Ketoglutarate
SH
Alanine
aminotransferase
O
O
Thiolpyruvate
H2S
H3N
CH3
O
O
Cysteine
NADH
+
3-Mercaptopyruvate
sulfurtransferase
H2O
+
NH4
Glutamate
α-Ketoglutarate
O
CH3
THF
CoA S
OH
H3N
Serine
hydroxymethyl
transferase
O
O
Serine
2-Amino3-ketobutyrate
CoA lyase
CH3
O
H3N
NADH
O
CH3
O
Propionyl-CoA
N
O
H
CH2
S CoA
NADH
+ CO2
+
O
HN
O
O
O
O
H
CH3
Acetaldehyde
O
AMP
+ PPi
O
O
H2N
HN
CH3
CH2
α-Ketobutyrate
H
N
N5,N10-Methylene
Tetrahydrofolate
H2C
+
O
N
O
O
H3N
O
O
O
H
N
Serine
O
CH3
Acetyl-CoA
N
O
O
CoA S
H2O + NH4
O
N
O
CH3
Acetate
Acetyl-CoA
Synthetase 2
Threonine
α-Ketoacid
dehydrogenase
Serine
hydroxymethyl
transferase
Aldehyde
dehydrogenase
ATP
+ CoA-SH
CH3
Threonine
dehydratase
NAD
+
CoA-SH
O
CH2
O
H
N
Tetrahydrofolate
(THF)
H3N
O
OH
Threonine
dehydrogenase
OH
H
HN
Serine
hydroxymethyl
transferase
NAD
FADH2
O
H3N
2-Amino-3-ketobutyrate
H
H
NH4 + O C O
Glycine
cleavage enzyme
(Glycine synthase)
O
Glycine
CH3
O
N
O
FAD
CoA-SH
H
N5,N10-Methylene
Tetrahydrofolate
O
Acetyl-CoA
N
NAD
+
THF
N5,N10-Methylene
Tetrahydrofolate
H3N
Alanine
Serine
O
O aminotransferase O
O
dehydratase
Alanine
Pyruvate
H2N
SH
H3N
O
Glycine
O
Metabolism of Phenylalanine and Tyrosine
H
OH
OH
TetrahydroH
biopterin
Pterin-4a+
carbinolamine
O2
H3N
H3N
CH2
O
O
Phenylalanine
α-Ketoglutarate Glutamate
Phenylalanine
hydroxylase
CH2
O
Tyrosine
aminotransferase
O
O
Tyrosine
O
O
p-Hydroxy
phenylpyruvate
p-Hydroxy
phenylpyruvate
hydroxylase
O
O
O
+
O
Fumarate
3 steps
O
Phenylalanine
hydroxylase
OH
N
O
H
CH3
OH
NADP
Pterin-4a-carbinolamine
H
H
H2N
N
N
H
OH
H
N
N
CH3
O
O
H
OH
H
H2O
NADPH
Dihydropteridine
reductase
O
Tyrosine
H
HN
CO2 + H2O
Dihydroascorbate
O
Homogentisate OH
Acetoacetate
O2
+
Phenylalanine
Tetrahydrobiopterin
H
H
H2N
N
N
H
Ascorbate + O2
OH
O
O
CH2
H
HN
N
N
H
H
Pterin-4a-carbinolamine
dehydratase
OH
H
HN
N
O
CH3
OH
7,8-Dihydrobiopterin
(quinoid form)
Branched-chain Amino Acids
H3N
H3N
O
O
Valine
H3N
O
O
Isoleucine
O
O
Leucine
α-Ketoglutarate
Branched-chain
amino acid
aminotransferase
α-Ketoglutarate
Branched-chain
amino acid
aminotransferase
Glutamate
O
Branched-chain
α-ketoacid
dehydrogenase
Branched-chain
amino acid
aminotransferase
Glutamate
O
O
O
α-Ketoisovalerate
S CoA
Isobutyryl-CoA
Glutamate
O
O
O
α-Keto-β-methylvalerate
NAD + CoA-SH
Branched-chain
α-ketoacid
dehydrogenase
NADH + CO2
O
α-Ketoglutarate
O
O
α-Ketoisocaproic acid
NAD + CoA-SH
Branched-chain
α-ketoacid
dehydrogenase
NADH + CO2
O
S CoA
α-Methylbutyryl-CoA
4 steps
5 steps
Propionyl-CoA
+
Acetyl-CoA
Propionyl-CoA
NAD + CoA-SH
NADH + CO2
O
S CoA
Isovaleryl-CoA
4 steps
Acetoacetate
+
Acetyl-CoA
Arginine, Proline, and Histidine Conversion to Glutamate
NH2
HN
Arginine
C
N
O
NH2
O
1/
2
NH
Histidine
N Proline
H2
H3N
O2
H3N
O
O
O
O
C
NH2
Urea
Pyrroline5-carboxylate
O
Arginase
NH2
Histidine
ammonia lyase
H2O
H2O
N
H
N
Urocanate
H2O
α-Ketoglutarate
NH4
NH
NH3
H3N
O
O
Proline oxidase
Non-enzymatic
O
O
H2O
Glutamate
Ornithine O
O
O
Ornithine
δ-aminotransferase
urocanate hydratase
H
N
H3N
NH
O
O
4-Imidazolone5-propionate
O
Glutamate
γ-semialdehyde
O
O
NAD(P)
H2O
Glutamate
5-semialdehyde
dehydrogenase
O
NAD(P)H
O
N5-FormiminoTHF
THF
imidazolone
propionase
O
HN
H3N
O
O
HN
O
Glutamate
glutamate-formiminotransferase
O
O
N-Formiminoglutamate
Tryptophan and Lysine
O
H
NH
NH
CH2
O
H2O
H
NH2
O
O
O2
H3N
O
H3N
Tryptophan
2,3-dioxygenase
O
O
Tryptophan
O
CH2
Formamidase
O
H3N
O
N-Formyl
kynurenine
CH2
O
Kynurenine
O2 + NADPH
Kynurenine
3-monooxygenase
H2O + NADP
OH
Nicotinic
acid
(Niacin) O
NH2
O
OH
Many
steps
NH2
O
N
O
H3N
H3N
+
O
O
Alanine
Kynureninase
[PLP]
O
O
O
Lysine
NH3
4 steps
O
O
2 α-Keto2
glutarate Glutamate
O
O
7 steps
O
O
α-Ketoadipate
O
CH2
O
3-Hydroxy
kynurenine
6 steps
H3N
O
H2O
CH3
O
Acetoacetate
Methionine and S-Adenosylmethionine
NH2
Adenosine Triphosphate
(ATP)
N
N
N
O
O
O
N
O P O P O P O CH2 O
O
O
H3N
O
H
OH
CH3
O
+
O
O
Methionine
OH
NH2
S-Adenosyl
methionine
CH3
S
S
O
Methionine
adenosyl
transferase
N
N
N
N
CH2 O
+
OH
Cobalamin
O
+
O
O P O P OH
O
O
Inorganic
phosphate
NH3
OH
O
O P OH
O
Pyrophosphate
R
Methionine
synthase
Methyl
transferase
Methylcobalamin
R CH3
NH2
Adenosine
O
O
SH
O
NH3
S
O
hydrolase
N
N
H2O
N
N
CH2 O
S-Adenosyl
homocysteine
NH3
Homocysteine
OH
OH
NH2
O
H2N
N
HN
H
N
N5,N10-methylene
Tetrahydrofolate
H2N
N
O
H2C
HN
O
NADH
N
O
O
NAD
O
H
N
O
N
N5,N10-methylene
Tetrahydrofolate
reductase
H
N
NH2
O
N5-methyl
Tetrahydrofolate
O
HN
CH3
O
NH2
O
Co3+
N
O
Methionine
synthase
N
NH2
O
THF
NH2
N
N
O
Cobalamin
O
H
N
O
O
H2N
N
O
CH3
HN
N
O
O P O
HO N
O
O
HO
Methylcobalamin
O
Folic Acid
H2N
N
Folic Acid
N
HN
p-Amino
benzoic
acid
N
Pterin
O
HN
O
O
H
N
N5
N10
O
Glutamate
O
O
H2N
O
S
O
NH2
Sulfanilamide
H2N
N
N
HN
NADPH
N
O
HN
H
NADP
H2N
N
HN
O
H2N
HN
O
Folic Acid
O
H3C
O
O
O
CH3
H2N
N
NH2
N
N
HN
O
H
N
O
H
H2N
HN
Trimethoprim
H2N
N
O
H
N
O
O
O
N
HN
O
Methotrexate
H
H
H
N
H
HN
R
Tetrahydrofolate
(THF)
N
H3C
N
O
R
N
NH2
N
HN
Dihydrofolate
N
CH3 O
NADP
Dihydrofolate
reductase
N
R
N
O
N
HN
Dihydrofolate
reductase
Folic Acid
H2N
N
H NADPH
H
N
N
NH2
O
HN
O
H
N
Aminopterin
O
O
O
Folic Acid Metabolism
H
H2N
N
H
HN
N
O
H
HN
Tetrahydrofolate
(THF)
Tetrahydrofolate
R
Glycine
+ NAD
Methylcobalamin
Serine
Glycine
cleavage enzyme
(Glycine synthase)
Methionine
synthase
Serine
hydroxymethyl
transferase
CO2 + NH4
+ NADH
Cobalamin
H2N
H
H
N
N
HN
H
N
NAD
NADH
H2N
H
N
N
HN
N
O
Glycine
HN
CH3
N5-Methyl
Tetrahydrofolate
R
(CH3OH)
N5,N10-Methylene
THF
reductase
Histidine
N
O
N
H2C
N5,N10-Methylene
Tetrahydrofolate
R
(CH2=O)
Tetrahydrofolate
N-Formiminoglutamate
NADP
N5-N10-Methenyl
THF reductase
Glutamate-formiminotransferase
NADPH
H2N
NH4
H
N
N
HN
H2N
N
HN
N
O
Glutamate
N
HC
N5,N10-Methenyl
Tetrahydrofolate
R
N5-Formimino
THF cyclodeaminase
(HCOOH)
ADP
+ Pi
H
N
N
O
HC
HN
NH
R
N5-Formimino
(HCOOH)
Tetrahydrofolate
ATP
O
C
H
O
Formate
+ ATP
ADP
+ Pi
H2N
N
HN
Tetrahydrofolate
N10-Formyl
THF
synthetase
O
ADP
+ Pi
H
N
N
H
HC
ATP
H2N
N
HN
N
N10-Formyl
R
THF
isomerase
O
N10-Formyl
(HCOOH)
Tetrahydrofolate
H
N
N
O
HC
HN
O
R
N5-Formyl
(HCOOH)
Tetrahydrofolate