DEAMINATION OF AMINO ACIDS - THE UREA CYCLE

+
-OOCCH CH COCOO-
2 2
R.CH(NH3)COO-
2-Oxoglutarate 2.6.1.42
AMINO ACID 2-Oxoglutarate
MAINLY VALINE, LEUCINE,
& ISOLEUCINE
+
-OOCCH CH CH(NH -
(Branched Chain Amino Acids)
-OOCCH CH CH(NH +)COO-
2 2 3)COO 2 2
RCOCOO- 3
Glutamate 2-Oxo Acid Glutamate
(Branched Chain)
LYSIS Pyruvate
CO Catabolism or Purine
G
LY Transport to Liver ATP NH4+ Nucleotide
Cycle
Serine 2.6.1.2 6.3.1.2
Glucose 2-Oxoglutarate ADP+Pi
Cysteine (?)
Malate + +
CH3CH(NH3)COO
- H2NOOCCH2CH2CH(NH3)COO-
Alanine MUSCLE Glutamine
GLUCOSE
ALANINE
CYCLE
Alanine Glutamine
LIVER
+
2.6.1.2 -OOCCH CH COCOO-
2 2 R.CH(NH3)cOO-
2-Oxoglutarate AMINO ACID

Alanine
Pyruvate 2-Oxo acid
Glucose
Catabolism or
GLUTAMATE Gluconeogenesis
G
S

L I
U S
GLUTAMATE +
CO E H2NOOCCH2CH2CH(NH3)COO-
NEO GEN
NAD(P)+ Glutamine
Pyruvate Oxidative 1.4.1.3
deamination NAD(P)H+H+ REACTANTS PRODUCTS H 2O
2.6.1.2

Mitochondrial Outer Membrane

NH4+ 3.5.1.2

Mitochondrial Inner Membrane

Alanine 2-Oxoglutarate
NH4+

Mitochondrial Matrix

Liver Cell Membrane

HCO3-
+
-OOCCH CH CH(NH -
N-Acetylglutamate 6.3.4.16 2ATP 2 2 3)COO
CH3CO.SCoA 2ADP Glutamate
HSCoA

SMALL INTESTINE
+ + O Oxaloacetate
H3N(CH2)3CH(NH3)COO- H2N-C-OP Pi
ORNITHINE Carbamoyl-P 2.6.1.1

2-Oxoglutarate
2.1.3.3 +
UREA Pi -OOCCH CH(NH
2 3) COO
-
CYCLE CITRULLINE ASPARTATE

O + -OOCCH CH COO-
ORNITHINE H2N-C-HN(CH2)3CH(NH3)COO- 2
+
CITRULLINE NH3 2-Oxoglutarate
NO Aspartate
-OOCCH CHCOO_ 2.6.1.1
2 6.3.4.5 ATP
Glutamate
NH AMP
+ + -OOCCH COCOO_
H2N=C-HN(CH2)3CH(NH3)COO- 2
1.5 NADPH+H+ PPi Oxaloacetate
Argininosuccinate
1.14.13.39
1.5 NADP+ NADH+H+
Glutam

4.3.2.1 -OOCCH=CHCOO_ -OOCCH CH(OH)COO_

2
Fumarate Malate 1.1.1.37
NH2
+ + 4.2.1.2 NAD+
H2N=C-HN(CH2)3CH(NH3)COO-
ine

1.5O2 ARGININE H2O

3.5.3.10
+ + H2NCONH2
H3N(CH2)3CH(NH3)COO-
ORNITHINE UREA

Glutamine
UREA CYCLE EQUATION Urea 3.5.1.2
+ NH4+
NH4+ + HCO3- + -OOCCH2CH(NH3)COO- + 3ATP H2NCONH2 + -OOCCH=CHCOO- + 2ADP + 2Pi + AMP + PPi
KIDNEY

Aspartate UREA Fumarate Glutamate

NH4+
1.4.1.3
Pyrophosphate (PPi) is rapidly hydrolysed so 4 high-energy phosphates from ATP are needed to form 1 urea
2-Oxoglutarate
Red and Blue arrows denote pathways of amino groups from amino acids to urea
Glucose
1.1.1.37 Malate dehydrogenase 2.6.1.2 Alanine aminotransferase 4.2.1.2 Fumarate hydratase
1.4.1.3 Glutamate dehydrogenase (NAD(P)) 2.6.1.42 Branched-chain amino acid 4.3.2.1 Argininosuccinate lyase
1.14.13.39 Nitric oxide synthase aminotransferase 6.3.1.2 Glutamine synthase
2.1.3.3 Ornithine carbamoyltransferase 3.5.1.2 Glutaminase 6.3.4.5 Argininosuccinate synthase
2.6.1.1 Aspartate aminotransferase 3.5.3.10 Arginase 6.3.4.16 Carbamoyl-phosphate synthase