DEAMINATION OF AMINO ACIDS - THE UREA CYCLE

-OOCCH CH COCOO2 2

2-Oxoglutarate

2.6.1.42

+ -OOCCH CH CH(NH )COO2 2 3

MAINLY VALINE, LEUCINE, & ISOLEUCINE (Branched Chain Amino Acids)

AMINO ACID
RCOCOO-

R.CH(NH3)COO-

2-Oxoglutarate
-OOCCH CH CH(NH +)COO2 2 3

Glutamate

LYSIS CO LY G

Pyruvate
2.6.1.2

2-Oxo Acid (Branched Chain)

Catabolism or Transport to Liver

Glutamate

ATP
6.3.1.2 ADP+Pi

Glucose

Serine Cysteine (?) Malate

NH4+ Nucleotide Cycle

+

Purine

2-Oxoglutarate

+ CH3CH(NH3)COO

Alanine

MUSCLE

H2NOOCCH2CH2CH(NH3)COO-

Glutamine

GLUCOSE ALANINE CYCLE

Alanine
2.6.1.2

LIVER
-OOCCH CH COCOO2 2

Glutamine
R.CH(NH3)cOO-

2-Oxoglutarate

AMINO ACID 2-Oxo acid

Alanine

Glucose
L

Pyruvate GLUTAMATE
S
G
U

Catabolism or Gluconeogenesis

CO

NEO GEN Pyruvate

GLUTAMATE
NAD(P)+ Oxidative 1.4.1.3 deamination NAD(P)H+H+ REACTANTS PRODUCTS

+ H2NOOCCH2CH2CH(NH3)COO-

Glutamine

Alanine

2.6.1.2 2-Oxoglutarate

NH4+
6.3.4.16

NH4+

3.5.1.2
+ -OOCCH CH CH(NH )COO2 2 3

H2O

Mitochondrial Outer Membrane Mitochondrial Inner Membrane

Mitochondrial Matrix

Liver Cell Membrane

N-Acetylglutamate
CH3CO.SCoA HSCoA

HCO32ATP 2ADP Pi

Glutamate

SMALL INTESTINE

O + + H3N(CH2)3CH(NH3)COO- H2N-C-OP

Oxaloacetate
2.6.1.1

ORNITHINE

Carbamoyl-P
2.1.3.3

2-Oxoglutarate

UREA CYCLE
ORNITHINE NO
O

Pi

+ -OOCCH CH(NH ) COO2 3

CITRULLINE
+
-OOCCH CH COO2

ASPARTATE

H2N-C-HN(CH2)3CH(NH3)COO-

CITRULLINE

-OOCCH CHCOO_ 2 + NH

Aspartate
ATP AMP
PPi
-OOCCH=CHCOO_

NH3

2-Oxoglutarate
2.6.1.1

6.3.4.5
+

Glutamate Oxaloacetate
-OOCCH CH(OH)COO_ 2 -OOCCH COCOO_ 2

1.5 NADPH+H+ 1.14.13.39 1.5 NADP+

H2N=C-HN(CH2)3CH(NH3)COO-

Argininosuccinate
4.3.2.1

NADH+H+ 1.1.1.37 NAD+

Glutam

NH2 + + H2N=C-HN(CH2)3CH(NH3)COO1.5O2 + + H3N(CH2)3CH(NH3)COO-

Fumarate

Malate

4.2.1.2

ine

ARGININE

H2O
H2NCONH2

3.5.3.10

ORNITHINE

UREA

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

Glutamine Urea 3.5.1.2

NH4+

KIDNEY

Aspartate

UREA

Fumarate

Pyrophosphate (PPi) is rapidly hydrolysed so 4 high-energy phosphates from ATP are needed to form 1 urea

NH4+

Glutamate

1.4.1.3

2-Oxoglutarate

Red and Blue arrows denote pathways of amino groups from amino acids to urea
Glucose
1.1.1.37 1.4.1.3 1.14.13.39 2.1.3.3 2.6.1.1 Malate dehydrogenase Glutamate dehydrogenase (NAD(P)) Nitric oxide synthase Ornithine carbamoyltransferase Aspartate aminotransferase

2.6.1.2 Alanine aminotransferase 2.6.1.42 Branched-chain amino acid aminotransferase 3.5.1.2 Glutaminase 3.5.3.10 Arginase

4.2.1.2 Fumarate hydratase

4.3.2.1 Argininosuccinate lyase 6.3.1.2 Glutamine synthase 6.3.4.5 Argininosuccinate synthase 6.3.4.16 Carbamoyl-phosphate synthase

Designed by Donald Nicholson