Amino acid catabolism

Distinquish between essential and non-essential amino acids.

Describe the mechanism of transamination.
List other compounds which are synthesised from amino acids.
Fate of the keto or carbon skeletons of deaminated amino acids.
Describe the steps in the urea cycle, ie carbamoyl phosphate synthesis,
citrulline formation, etc

Refer to chapter 23, Stryer, 5e and chapter 18, Lehninger,

4e.
Lecture 28, Michael Schweizer

Overview of amino acid catabolism in mammals.

Amino group catabolism.

H
R1 C COO

R2

NH3

C COO

O
Transaminase
H

R1 C COO
O

R2

C COO

NH3

Transaminase enzymes (aminotransferases) catalyze

the reversible transfer of an amino group between
two -keto acids.

Transaminase Roles
Transaminases equilibrate amino groups among
available -keto acids.
This permits synthesis of non-essential amino acids,
using amino groups from other amino acids & carbon
skeletons synthesized in a cell. Thus a balance of
different amino acids is maintained, as proteins of
varied amino acid contents are synthesized.
Although the amino N of one amino acid can be used
to synthesize another amino acid, N must be
obtained in the diet as amino acids (proteins).

COO

COO

COO

CH2

COO

CH2

CH2

CH2

CH2

CH2

HC

NH3+

COO

COO

COO

HC

NH3+

COO

aspartate -ketoglutarate oxaloacetate glutamate

Aminotransferase (Transaminase)

Example of a Transaminase reaction:

Aspartate donates its amino group, becoming the
-keto acid oxaloacetate.
-Ketoglutarate accepts the amino group,
becoming the amino acid glutamate.

H
O

P
O

H2
C

O
OH

N
H

CH3

pyridoxal phosphate (PLP)

The prosthetic group of Transaminase is

pyridoxal phosphate (PLP), a derivative of
vitamin B6.

Amino acid

-keto acid

-ketoglutarate

glutamate

Transaminase

NADH + NH4+

NAD+ + H2O

Glutamate
Dehydrogenase

Summarized above: the role of transaminases in

funneling amino N to glutamate, which is deaminated
via Glutamate Dehydrogenase, producing NH4+.

O
H2N

NH2

urea

Most terrestrial land animals convert excess nitrogen to

urea, prior to excreting it. Urea is less toxic than
ammonia.
The Urea Cycle occurs mainly in liver.
The 2 nitrogen atoms of urea enter the Urea Cycle as NH3
(produced mainly via Glutamate Dehydrogenase) and as
amino N of aspartate.
The NH3 and HCO3 (carbonyl C) that will be part of urea
are incorporated first into carbamoyl phosphate.

Nitrogen-acquiring
reactions in the
synthesis of urea.

HCO3

Carbamoyl Phosphate
Synthetase (Type I)
catalyzes a 3-step reaction,
with carbonyl phosphate
and carbamate
intermediates.
NH3 is the N input.
The reaction, which
involves cleavage of 2 ~P
bonds of ATP, is essentially
irreversible.

ATP
ADP
O
HO
NH3
Pi
H2N

OPO32

carbonyl phosphate

O
C

ATP
ADP

carbamate

O
H2N

OPO32

carbamoyl phosphate

Links between the urea cycle and citric acid cycle.

Glucogenic acids are shaded red, ketogenic ones are shaded yellow. Most
amino acids are both glucogenic and ketogenic.