METABOLISME ASAM AMINO Protein Biologi

METABOLISME PROTEIN
DAN ASAM AMINO
(DEGRADASI ASAM AMINO)

THE PATHWAYS OF AMINO ACID CATABOLISM ARE QUITE
SIMILAR IN MOST ORGANISMS.
In animals, amino acids undergo oxidative degradation in three different

metabolic circumstances:
1. During the normal synthesis and degradation of cellular proteins
(protein turnover) some amino acids that are released from protein
breakdown and are not needed for new protein synthesis undergo
oxidative degradation.
2. When a diet is rich in protein and the ingested amino acids exceed the
body’s needs for protein synthesis, the surplus is catabolized; amino
acids cannot be stored.
3. During starvation or in uncontrolled diabetes mellitus, when

carbohydrates are either unavailable or not properly utilized, cellular
proteins are used as fuel.
Metabolic Fates of Amino Groups
Dietary Protein Is Enzymatically Degraded to Amino Acids
STEPS IN THE CATABOLISM OF MOST L-AMINO ACIDS
(BIOSYNTHESIS OF UREA)
Urea biosynthesis occurs in four stages:

(1) transamination,
(2) oxidative deamination of glutamate,
(3) ammonia transport, and
(4) reactions of the urea cycle
1. TRANSAMINATION
once L-amino acids have reached the liver, is removal of the - amino groups,
promoted by enzymes called aminotransferases or transaminases
Aminotransferases are classic examples of enzymes catalyzing
bimolecular Ping-Pong reactions
a b
(a) close-up view of the active site, with PLP (red,

with yellow phosphorus) in aldimine linkage with
PLP (red) bound to one of the two the side chain of Lys258 (purple);
active sites of the dimeric enzyme (b) another close-up view of the active site, with
aspartate aminotransferase, a PLP linked to the substrate analog 2-
typical aminotransferase methylaspartate (green) via a Schiff base (PDB ID
1AJS).
Measurement Of The Alanine Aminotransferase And Aspartate
Aminotransferase Levels In Blood Serum Is Important In Some Medical
Diagnoses.
(2) OXIDATIVE DEAMINATION OF GLUTAMATE
Glutamate Releases Its Amino Group as Ammonia in the Liver

In hepatocytes, glutamate is transported from the cytosol into
mitochondria, where it undergoes oxidative deamination catalyzed by
Lglutamate dehydrogenase (Mr 330,000).
In mammals, this enzyme is present in the mitochondrial matrix.
It is the only enzyme that can use either NAD or NADP as the acceptor
of reducing equivalents
The α -ketoglutarate formed from glutamate deamination can be used

in the citric acid cycle and for glucose synthesis.
(3) AMMONIA TRANSPORT
(A) Glutamine Transports Ammonia in the Bloodstream
Ammonia is quite toxic to animal and the levels present in blood are
regulated
In many tissues,including the brain, some processes such as nucleotide

degradation generate free ammonia.
In most animals much of the free ammonia is converted to a nontoxic

compound before export from the extrahepatic tissues into the blood and
transport to the liver or kidneys.
For this transport function, glutamate, critical to intracellular amino

group metabolism, is supplanted by L-glutamine.
The free ammonia produced in tissues is combined with glutamate to

yield glutamine by the action of glutamine synthetase
REAKSI
PEMBENTUKAN
GLUTAMIN
(B) Alanine Transports Ammonia
from Skeletal Muscles to the Liver
Alanine also plays a special role in

transporting amino groups to the
liver in a nontoxic form, via a
pathway called the glucose-alanine
cycle
In muscle and certain other tissues
that degrade amino acids for fuel,
amino groups are collected in the form
of glutamate by transamination
FIGURE 18–9 Glucose-alanine cycle.

Alanine serves as a carrier of ammonia
and of the carbon skeleton of pyruvate
from skeletal muscle to liver. The
ammonia is excreted and the pyruvate
is used to produce glucose, which is
returned to the muscle.
(4) REACTIONS OF THE UREA CYCLE
 In ureotelic organisms, the ammonia deposited in the mitochondria of

hepatocytes is converted to urea in the urea cycle
 This pathway was discovered in 1932 by Hans Krebs (who later also
discovered the citric acid cycle) and a medical student associate, Kurt
Henseleit.
 Urea production occurs almost exclusively in the liver and is the fate of
most of the ammonia channeled there.
 The urea passes into the bloodstream and thus to the kidneys and is
excreted into the urine
Urea cycle
UREA IS PRODUCED FROM AMMONIA IN FIVE ENZYMATIC STEPS
The urea cycle begins inside liver mitochondria, but three of the
subsequent steps take place in the cytosol; the cycle thus spans two cellular
compartments
The first amino group to enter the urea cycle is derived from ammonia in
the mitochondrial matrix—NH4+ arising by the pathways of oxidative
deamination of glutamat
NH4 generated in liver mitochondria is immediately used, together with CO 2
(as HCO3 ) produced by mitochondrial respiration, to form carbamoyl
phosphate (an activated carbamoyl group donor, now enters the urea cycle).
in the matrix catalyzed by carbamoyl phosphate synthetase I
The cycle has four enzymatic steps
First, carbamoyl phosphate donates its carbamoyl group to ornithine to

form citrulline, with the release of Pi catalyzed by Ornithine
Transcarbamoylase and the citrulline passes from the mitochondrion to
the cytosol.
The second amino group now enters from aspartate (generated in

mitochondria by transamination and transported into the cytosol) by a
condensation reaction between the amino group of aspartate and the
ureido (carbonyl) group of citrulline, forming argininosuccinate catalyzed
by argininosuccinate synthetase, requires ATP and proceeds through a
citrullyl-AMP intermediate
The argininosuccinate is then cleaved bynargininosuccinase to form free
arginine and fumarate, the latter entering mitochondria to join the pool of
citric acid cycle intermediates. This is the only reversible step in the urea
cycle.
In the last reaction of the urea cycle (step 4 ), the cytosolic enzyme arginase
cleaves arginine to yield urea and ornithine. Ornithine is transported into the
mitochondrion to initiate another round of the urea cycle.
PATHWAYS OF AMINO ACID DEGRADATION
The pathways of amino acid catabolism, taken

together,normally account for only 10% to 15% of the human
body’s energy production; these pathways are not nearly as
active as glycolysis and fatty acid oxidation
The 20 catabolic pathways converge to form only six

major products, all of which enter the citric acid cycle
From here the carbon skeletons are diverted to

gluconeogenesis or ketogenesis or are completely oxidized
to CO2 and H2O.
Summary of amino acid catabolism
A. Six Amino Acids Are Degraded to Pyruvate
B. Seven Amino Acids Are Degraded to Acetyl-CoA (tryptophan, lysine, phenylalanine,
tyrosine, leucine, isoleucine, and threonine )
The degradative pathways of two of these seven amino acids deserve special mention
1. Tryptophan breakdown is the most complex of all the pathways of amino acid
catabolism in animal tissues; portions of tryptophan (four of its carbons) yield
acetyl-CoA via acetoacetyl- CoA
Some of the intermediates in

tryptophan catabolism are
precursors for the synthesis of
other biomolecules including
nicotinate, a precursor of NAD
and NADP in animals;
serotonin, a neurotransmitter
in vertebrates; and
indoleacetate, a growth factor
in plants.
2. The breakdown of phenylalanine is noteworthy because genetic defects in the
enzymes of this pathway lead to several inheritable human diseases
Phenylalanine Catabolism Is Genetically Defective in Some People
Genetic defect in
phenylalanine hydroxylase
(phenylalanine- 4-
monooxygenase), the first
enzyme in the catabolic
pathway for phenylalanine is
responsible for the disease
phenylketonuria (PKU), the
most common cause of
elevated levels of
phenylalanine
(hyperphenylalaninemia).
C. Five Amino Acids Are Converted to -Ketoglutarate
D. Four Amino Acids Are Converted to Succinyl-CoA
E. Asparagine and Aspartate Are Degraded to Oxaloacetate
SUMMARY Pathways of Amino Acid Degradation
■ After removal of their amino groups, the carbon skeletons of amino acids undergo
oxidation to compounds that can enter the citric acid cycle for oxidation to CO 2 and H2O.
■ Depending on their degradative end product, some amino acids can be converted to
ketone bodies, some to glucose, and some to both. Thus amino acid degradation is
integrated into intermediary metabolism and can be critical to survival under conditions
in which amino acids are a significant source of metabolic energy.
■ The carbon skeletons of amino acids enter the citric acid cycle through five
intermediates: acetyl-CoA, -ketoglutarate, succinyl-CoA, fumarate, and oxaloacetate.
Some are also degraded to pyruvate, which can be converted to either acetyl-CoA or
oxaloacetate.
■ The amino acids producing pyruvate are alanine, cysteine, glycine, serine, threonine,
and tryptophan. Leucine, lysine, phenylalanine, and tryptophan yield acetyl-CoA via
acetoacetyl-CoA. Isoleucine, leucine, threonine, and tryptophan also form acetyl-
CoA directly.
■ Arginine, glutamate, glutamine, histidine, and proline produce -ketoglutarate;
isoleucine, methionine, threonine, and valine produce succinyl-CoA; four
carbon atoms of phenylalanine and tyrosine give rise to fumarate; and
asparagine and aspartate produce oxaloacetate.
■ A number of serious human diseases can be traced to genetic defects in the enzymes
of amino acid catabolism.

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METABOLISME PROTEIN

DAN ASAM AMINO

(DEGRADASI ASAM AMINO)

In animals, amino acids undergo oxidative degradation in three different

3. During starvation or in uncontrolled diabetes mellitus, when

Urea biosynthesis occurs in four stages:

(a) close-up view of the active site, with PLP (red,

Glutamate Releases Its Amino Group as Ammonia in the Liver

The α -ketoglutarate formed from glutamate deamination can be used

(A) Glutamine Transports Ammonia in the Bloodstream

In many tissues,including the brain, some processes such as nucleotide

In most animals much of the free ammonia is converted to a nontoxic

For this transport function, glutamate, critical to intracellular amino

The free ammonia produced in tissues is combined with glutamate to

Alanine also plays a special role in

FIGURE 18–9 Glucose-alanine cycle.

 In ureotelic organisms, the ammonia deposited in the mitochondria of

First, carbamoyl phosphate donates its carbamoyl group to ornithine to

The second amino group now enters from aspartate (generated in

The pathways of amino acid catabolism, taken

The 20 catabolic pathways converge to form only six

From here the carbon skeletons are diverted to

Some of the intermediates in

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