4) Amino Acid Breakdown Handout - Rose-Hulman - Top Ranked
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Amino Acid Breakdown H 3 N O O H 3 N O O H 3 N O O OH H 3 N O O H 3 N O O Leucine Valine Isoleucine Threonine Methionine H 3 N O O Phenylalanine H 3 N O O Tryptophan H 3 N O O Lysine NH NH 3 H 3 N O O Tyrosine H 3 N O O SH Cysteine H 3 N O O Arginine H 3 N O O Histidine OH NH NH 2 H 2 N NH N H 3 N O O Glycine H 3 N O O Alanine H 3 N O O OH Serine H 3 N O O Aspartate O O H 3 N O O Asparagine NH 2 O H 3 N O O Glutamate O O H 3 N O O Glutamine O H 2 N N H 2 O O Proline S Nutritionally Essential Conditionally Nutritionally Essential Nutritionally Non-essential
Transcript of 4) Amino Acid Breakdown Handout - Rose-Hulman - Top Ranked
Amino Acid Breakdown
H3NO
OH3N
O
OH3N
O
O
OH
H3NO
OH3N
O
OLeucine Valine Isoleucine Threonine Methionine
H3NO
OPhenylalanine
H3NO
OTryptophan
H3NO
OLysine
NH
NH3
H3NO
OTyrosine
H3NO
O
SH
Cysteine
H3NO
OArginine
H3NO
OHistidine
OH NH
NH2H2N
NHN
H3NO
OGlycine
H3NO
OAlanine
H3NO
O
OH
Serine
H3NO
OAspartate
O
O
H3NO
OAsparagine
NH2
O
H3NO
OGlutamate
OO
H3NO
OGlutamine
OH2N
NH2
O
OProline
S
Nutritionally Essential
Conditionally Nutritionally Essential
Nutritionally Non-essential
Alanine Cycle
Overview of Nitrogen Flow
Pyruvate Glucose Glucose
Pyruvate
Alanine
Protein
Amino acidsα-ketoacids
AlanineNH4
Glutamine Branched-chainamino acids
Urea
MuscleLiver
UreaExcretionProducts
NH4Kidney
Alanine cycle
Brain
2 ATP4 ATP + 2 GTP
Ornithine
Fumarate Oxaloacetate
α-amino acid
α-ketoacid
Urea CycleH2NC
O
NH2
Urea
N-acetylglutamate
Aspartate
NH4+
α-amino acid
α-ketoacid
α-ketoglutarate
Glutamate
NAD(P)NAD(P)H
+ α-ketoglutarateAmino-
transferase
Amino-transferase
Glutamatedehydrogenase Carbamoyl
phosphatesynthase I
Glutamate Glutamine
Glutaminase
GlutaminesynthetaseATP
ADP+ Pi
H2O
α-amino acid
α-ketoacid+ H2O2
L-aminoacidoxidase[FAD]
Aminotransferases
SGOT (Serum Glutamate Oxaloacetate Transaminase) = AST (Aspartate aminotransferase) SGPT (Serum Glutamate Pyruvate Transaminase) = ALT (Alanine aminotransferase)
O O
O
O
O
+
O O
H3N
OO
Aspartateaminotransferase
α-Ketoglutarate Aspartate
O O
H3N
O
O
+
O O
O
OO
Glutamate Oxaloacetate
O O
O
O
O
+
O O
H3NAlanine
aminotransferase
α-Ketoglutarate Alanine
O O
H3N
O
O
+
O O
O
Glutamate Pyruvate
N
HO
H
CHN
O
Enzyme
H
P
O
O
O
RC
NH2
HO
OH
N
HO
H
CHN
O
Enzyme
H
P
O
O
O
RC
NH
HO
OH
N
HO
H
CH
O P
O
O
O
RC
NH
HO
OEnzyme
N
HO
H
CH2
O P
O
O
O
RC
NH
O
O
NH2
Enzyme
N
HO
H
CH2
O P
O
O
O
NH3NH2
EnzymeRC
O
OO
Hydrolysis
α-aminoacid
α-ketoacid
Loss ofα-carbonproton
H3C H3C H3C
H3CH3C N
HO
H
CH
O P
O
O
O
RC
NH
O
OEnzyme
H3C
NH2
NH2
H
Glutamate Dehydrogenase
Regulators: Inhibitors: NADH, GTP Activators: NAD, leucine, ADP Hyperinsulinemia/Hyperammonemia mutations Bovine Glutamate Dehydrogenase (PDB ID 3MW9)
O O
H3N
Glutamate
O
ONAD(P) NAD(P)H
O O
H2N
GlutamateDehydrogenase
O
OH2O NH4
O O
O
O
O
GlutamateDehydrogenase
α-Ketoglutarate
Glutamate + NAD α-ketoglutarate + NADH∆G´° = +30 kJ/mol
Bovine Glutamate Dehydrogenase (PDB ID 3MW9)
GTP
RegulatoryNADH
Glutamate
SubstrateNADH
GTP
RegulatoryNADH
Glutamate
SubstrateNADH
Overview of Amino Acid Breakdown
CO2
CO2
Acetyl-CoA
cis-Aconitate
Isocitrate
α-Ketoglutarate
Succinyl-CoA
Succinate
Tyrosine*Phenylalanine*
Propionyl-CoA
Glutamate
Isoleucine*MethionineValine
Threonine*
Histidine Proline
Glutamine
Glu
tam
ina
se
NH4
GlutamineG
luta
min
esy
nth
eta
se
NH4
Leucine*LysinePhenylalanine*Tryptophan*Tyrosine*
Acetoacetyl-CoA
Ketonebodies
Isoleucine*Leucine*Threonine*
CysteineGlycineSerineThreonine*Tryptophan*
CO2
Pyruvate
Alanine
Fumarate
Malate
Oxaloacetate
Asparagine
Aspartate
Ornithine
Arginine
Citrate
GlucogenicAlanineArginineAsparagineGlutamateGlutamineGlycineHistidineMethionineProlineSerineValine
KetogenicLeucine*Lysine
BothIsoleucine*
Phenylalanine*Threonine*
Tryptophan*Tyrosine*
* Denotes amino acids that enter the TCA cycle in more than one place
Bold denotes gluconeogenic amino acids
Italics denotes ketogenic amino acids
Bold italics denotes amino acids that are both glucogenic and ketogenic
Glutamine Metabolism
N-Acetylglutamate
H2O NH4
Glutaminase
O O
H3N
O
NH2
Glutamine
O O
H3N
Glutamate
O
O
O O
H3N
Glutamate
O
O ATP ADP
O O
H3N
O
O P
O
O
O
PiNH4
O O
H3N
O
NH2
Glutamine
GlutamineSynthetase
GlutamineSynthetase
O O
H3N
Glutamate
O
O
N-AcetylglutamateSynthase
Acetyl-CoA CoA-SH
O O
HN
N-Acetylglutamate
O
OCO
CH3
Urea Cycle
H2O
NH2
COO
P OO
O
O O
H3N
NH3
O
O
O
O Fumarate
O O
H3N
NH3
O O
H3N
HNC
NH2
O
O O
H3N
HNC
NH2
O
Ornithinetranscarbamoylase
Ornithine
Citrulline
Argininosuccinate
Arginine
Carbamoylphosphatesynthetase I
Argininosuccinate synthetase
Argininosuccinase
Arginase
OrnithineO
CO
OH
NH4
+
2 ADP+ Pi 2 ATP
MitochondrialMatrix
Cytoplasm
Pi
CitrullineO O
H3N
OAspartate O
ATPAMP+ PPi
O O
H3N
HNC
NH
O O
N
OO
H
O O
H3N
HNC
NH2
NH2
OC
NH2
NH2
Urea
Carbamoylphosphatesynthetase I
NH4
OCO
OH
ATP ADPOH
COO
P OO
O
Pi
OH
COH2N
ATP
ADP
NH2COO
P OO
O
Metabolism of Small Side-chain Amino Acids (Glycine, Serine, Cysteine, and Threonine)
Serinehydroxymethyl
transferase
O O
H3N
Glycine
N5,N10-MethyleneTetrahydrofolateTHF
NH4 + O C OGlycine
cleavage enzyme(Glycine synthase)
N5,N10-MethyleneTetrahydrofolate
NAD+
THF
NADH+
O O
H3N
OH
Serine
NH4
SerinedehydrataseO O
CH3O
Pyruvate
O O
H3N
OH
Threonine
CH3
Serinehydroxymethyl
transferaseH
O
CH3
Acetaldehyde
NADNADH
O O
H3N
O
2-Amino-3-ketobutyrate
CH3
Threoninedehydrogenase
CoA-SH
S
O
CH3CoA 2-Amino-3-ketobutyrateCoA lyase Aldehyde
dehydrogenase
FAD FADH2
O
O
CH3
Acetate
ATP+ CoA-SH
AMP+ PPi
Acetyl-CoASynthetase 2
S
O
CH3CoA
AlanineaminotransferaseO O
CH3H3N
Alanine
Glutamateα-Ketoglutarate
O O
H3N
SH
Cysteine
Alanineaminotransferase
Glutamate α-Ketoglutarate
O O
O
SH
Thiolpyruvate
H2S 3-Mercaptopyruvatesulfurtransferase
Acetyl-CoA
Acetyl-CoA
H2O+
NH4H2O +Threoninedehydratase
O O
CH2O
CH3
NAD+
CoA-SH
NADH+ CO2
Propionyl-CoA S
CH2O
CH3
CoA α-Ketobutyrateα-Ketoaciddehydrogenase
Tetrahydrofolate(THF)
O O
CH2H3N
OH
+
Serine
Serinehydroxymethyltransferase
O O
H3N+
Glycine
N5,N10-MethyleneTetrahydrofolate
HN
N
N
HN
N
O
HN
O O
O
O
H2N
O H2C
HN
N
N
N
HN
O
HN
O O
O
O
H2N
O H
H
HHH
Metabolism of Phenylalanine and Tyrosine
TyrosineaminotransferaseO O
CH2H3N
Tyrosine
Glutamateα-Ketoglutarate
O O
CH2H3N
Phenylalanine
Phenylalaninehydroxylase
O2
OH
O O
CH2O
p-Hydroxyphenylpyruvate
OH
CO2
p-Hydroxyphenylpyruvate
hydroxylase
OH
OH
Tetrahydro-biopterin
Pterin-4a-carbinolamine
Ascorbate
Dihydroascorbate
O2
H2O
O
O3 steps
O
OO
Acetoacetate
O
O
O
OFumarate
+
Homogentisate
H
H
+
+
+
HN
N
N
N
OH
H2N
O
H
HH
H
HCH3
OH
Tetrahydrobiopterin
N
N
N
N
OH
H2N
O
H
HH
H
HCH3
OH
Pterin-4a-carbinolamine
O
H
TyrosinePhenylalanine
Phenylalaninehydroxylase
O2+
HN
N
N
N
OH
HN
O
H
HH
HCH3
OH
H2OPterin-4a-carbinolaminedehydratase
7,8-Dihydrobiopterin(quinoid form)
NADP
NADPHDihydropteridine
reductase
Branched-chain Amino Acids
O O
H3N
LeucineO O
H3N
ValineO O
H3N
Isoleucine
Branched-chainamino acid
aminotransferase
Glutamate
α-Ketoglutarate
Branched-chainamino acid
aminotransferase
Glutamate
α-Ketoglutarate
Branched-chainamino acid
aminotransferase
Glutamate
α-Ketoglutarate
O O
O
O O
O
α-KetoisovalerateO O
O
α-Keto-β-methylvalerate α-Ketoisocaproic acid
NAD + CoA-SH
NADH + CO2
Branched-chainα-ketoaciddehydrogenase
NAD + CoA-SH
NADH + CO2
Branched-chainα-ketoaciddehydrogenase
NAD + CoA-SH
NADH + CO2
Branched-chainα-ketoaciddehydrogenase
S
O
S
O
S
O
α-Methylbutyryl-CoACoA CoA CoA
Isobutyryl-CoA Isovaleryl-CoA
4 steps 5 steps 4 steps
Acetoacetate+
Acetyl-CoA
Propionyl-CoAPropionyl-CoA+
Acetyl-CoA
Arginine, Proline, and Histidine Conversion to Glutamate
H2O
O O
H3N
NH3
Arginine
Arginase
Ornithine
O O
H3N
HNC
NH2
NH2
OC
NH2
NH2
Urea
Ornithineδ-aminotransferase
Glutamate
α-Keto-glutarate
O O
H3N
O
Glutamateγ-semialdehyde
H
NH2O
O
H2O
Proline oxidase
1/2 O2
NHO
O
Proline
H2O
Non-enzymatic
NAD(P)
NAD(P)H
Glutamate5-semialdehydedehydrogenase
O O
H3N
O
Glutamate
O
Histidine
O O
H3N
NH
N
NH4
Histidineammonia lyase
O O
NH
N
H2O
urocanate hydratase
O O
NH
N
O
H2O
O O
HN
O
N-Formiminoglutamate
OHNTHF
N5-Formimino-THF
imidazolonepropionase
glutamate-formimino-transferase
Pyrroline-5-carboxylate
Urocanate
4-Imidazolone-5-propionate
Tryptophan and Lysine
O O
CH2H3N
Tryptophan
NH
O O
CH2H3N
N-Formylkynurenine
O
NH
O H
O O
CH2H3N
Kynurenine
O
NH2
O H
O O
CH2H3N
3-Hydroxykynurenine
O
NH2
OH
O
NH2
OH
O
O2
Tryptophan2,3-dioxygenase
H2O O
Formamidase
O2 + NADPH
H2O + NADP
H2O
Kynureninase[PLP]O O
CH3H3N
Alanine
+
6 steps
Kynurenine3-monooxygenase
OO
O
O
O
α-Ketoadipate
7 stepsO
OO
AcetoacetateO O
H3N
Lysine
NH3 4 steps
2Glutamate
2 α-Keto-glutarate
N
O
O Manysteps
Nicotinicacid
(Niacin)
Methionine and S-Adenosylmethionine
P
O
O
O O P
O
O
O
OHOHH
CH2O
N
N N
N
NH2
P
O
O
O
Adenosine Triphosphate(ATP)
+ P
O
O
O OH
Inorganicphosphate
+ P
O
O
O O P
O
O
OH
Pyrophosphate
O
OHOH
CH2
N
N N
N
NH2
SO
O
NH3
CH3
O O
H3N
Methionine
SCH3
Methionineadenosyltransferase
+
Methyltransferase
R CH3
R
O
OHOH
CH2
N
N N
N
NH2
SO
O
NH3
H2OAdenosine
hydrolase
SHO
O
NH3
Homocysteine
Methyl-cobalamin
Cobalamin
Methioninesynthase
N5-methylTetrahydrofolate
HN
N
N
HN
HN
O
HN
O O
O
O
H2N
OCH3
N5,N10-methyleneTetrahydrofolate
HN
N
N
HN
N
O
HN
O O
O
O
H2N
O H2CNADNADH
Methylcobalamin
CH3
O
P
O
O O
O
HO
N
N
HO
NN
O NH2 NH2
O
NH2
O
NN
H2N
O
O
NH2
O
HN
Co3+
O
NH2
Cobalamin
THF
N5,N10-methyleneTetrahydrofolatereductase
Methioninesynthase
S-Adenosylmethionine
S-Adenosylhomocysteine
Folic Acid
HN
N
N
N
HN
O
HN
O O
O
O
H2N
O
Folic Acid
Pterin
p-Aminobenzoicacid
Glutamate
N5
N10
SNH2
O
O
H2N
Sulfanilamide
HN
N
N
N
HNR
H2N
O
HN
N
N
N
HN
H2N
OR
H
HH
HN
N
N
N
HN
H2N
OR
H
HH
H
H
NADPNADPH
Folic Acid Dihydrofolate Tetrahydrofolate(THF)
Dihydrofolatereductase
NADPNADPH
Dihydrofolatereductase
HN
N
N
N
HN
O
HN
O O
O
O
H2N
O
Folic Acid
HN
N
N
N
N
O
HN
O O
O
O
H2N
NH2
Methotrexate
H3C
HN
N
N
N
HN
O
HN
O O
O
O
H2N
NH2
Aminopterin
N
N
OCH3
O
CH3
OH3C
NH2H2N
Trimethoprim
Folic Acid Metabolism
Tetrahydrofolate(THF)
HN
N
N
N
HNR
H2N
O H
H
HH
H
HN
N
N
HN
NR
H2N
O H2C
N5,N10-MethyleneTetrahydrofolate
Glycine+ NAD
CO2 + NH4+ NADH
Glycinecleavage enzyme
(Glycine synthase)
Serinehydroxymethyltransferase
Serine
Glycine
N-Formimino-glutamate
Glutamate-formimino-transferase
Tetrahydrofolate
Glutamate
N5-N10-MethenylTHF reductase
NADP
NADPH
(CH2=O)
HN
N
N
HN
NR
H2N
O HC
N5,N10-MethenylTetrahydrofolate
(HCOOH)
HN
N
N
HN
HNR
H2N
O
N5-FormiminoTetrahydrofolate (HCOOH)
HCNH
Histidine
N5-FormiminoTHF cyclodeaminase
NH4
ATP
ADP+ Pi
HN
N
N
HN
HNR
H2N
O
N5-FormylTetrahydrofolate (HCOOH)
HCO
HN
N
NH
HN
NR
H2N
O
N10-FormylTetrahydrofolate (HCOOH)
ATP
ADP+ Pi
N10-FormylTHF
isomerase
HC
O
Tetrahydrofolate
HC
O
OFormate
+ ATP
ADP+ Pi
N10-FormylTHF
synthetase
N5,N10-MethyleneTHF
reductase
NADHNAD
HN
N
N
HN
HNR
H2N
O
N5-MethylTetrahydrofolate
(CH3OH)
CH3
Methyl-cobalamin
Cobalamin
Methioninesynthase
Tetrahydrofolate
