Metabolic Pathways for Protein

and Amino Acids

Dr. Lilia Dewiyanti, SpA,MsiMed

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I. Introduction
II. Digestion of Proteins
III. Degradation of Amino Acids
IV. Urea Cycle

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 I. Introduction
Proteins provide:
 Amino acids for

protein synthesis.
 Nitrogen atoms for

nitrogen-containing
compounds.
 Energy when

carbohydrate and
lipid resources are
not available.

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Functions of Proteins

4
II. Digestion of Proteins

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 Amino Acids Metabolism
Nonessential AA synthesis AA catabolism

Vitamin B6
AA L-glutamate
.
Transamniation

Oxidative deamination

Urea Blood

Kidney

Urine
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 Transamination
In transamination:
 Amino acids are degraded in the liver.

 An amino group is transferred from an amino

acid to an -keto acid, usually -ketoglutarate.

 The reaction is catalyzed by a transaminase or

aminotransferase.
 A new amino acid, usually glutamate, and a new

-keto acid are formed.

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 A Transamination Reaction

NH3+ O Alanine
| || aminotransferase
CH3—CH—COO- + -OOC—C—CH2—CH2—COO-

Alanine -Ketoglutarate

O NH3+
|| |
CH3—C—COO- + -OOC—CH—CH2—CH2—COO-
Pyruvate Glutamate

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 B. Oxidative Deamination
Oxidative deamination:
 Removes the amino group as an ammonium ion from

glutamate.
 Provides -ketoglutarate for transamination.

NH3+ Glutamate
| dehydrogenase
-OOC—CH—CH —CH —COO- + NAD+ + H O
2 2 2
Glutamate
O
||
-OOC—C—CH —CH —COO- + NH + + NADH
2 2 4
-Ketoglutarate

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 Urea Cycle
The urea cycle:
 Detoxifies ammonium ion from amino acid

degradation.
 Converts ammonium ion to urea in the liver.

O
||
H2N—C—NH2 urea
 Provides 25-30 g urea daily for urine
formation in the kidneys.
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Urea Cycle

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 Carbamoyl Phosphate
 In the mitochondria, an ammonium ion reacts
with CO2 from the citric acid cycle, 2 ATP,
and water.
NH4+ + CO2 + 2ATP + H2O
O O
|| ||
H2N—C—O—P—O- + 2ADP + Pi
|
O-
Carbamoyl phosphate

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 Reaction 1 Transfer of Carbamoyl
Group
 The carbamoyl group is transferred to
ornithine to form citrulline.
 Citrulline moves across the mitochondrial
membrane into the cytosol.

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 Reaction 2 Condensation with
Aspartate
 In the cytosol,
citrulline combines
with aspartate.
 Hydrolysis of ATP
to AMP provides
energy. Cytosol
 The N in aspartate
is part of urea.

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 Reaction 3 Cleavage of Fumarate
Fumarate:
 Is cleaved from argininosuccinate.

 Enters the citric acid cycle.

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 Reaction 4 Hydrolysis Forms
Urea
Hydrolysis of arginine:
 Forms urea.

 Forms ornithine,

which returns to the

mitochondrion to
pick up another
carbamoyl group to
repeat the urea cycle.

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Urea Cycle

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 Summary of Urea Cycle
The urea cycle converts:
 Ammonium ion to urea

 Aspartate to Fumarate

 3ATP to 2ADP, AMP, 4P

i

NH4+ + CO2 + 3ATP + Aspartate + 2H2O

Urea + 2ADP + AMP + 4Pi + Fumarate

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Fates of the Carbon Atoms from
Amino Acids

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 Carbon Atoms from Amino Acids
Carbon skeletons of amino acids are intermediates or
converted to intermediates for use in the citric acid
cycle.
 Three-carbon skeletons:
Alanine, serine, and cysteine Pyruvate
 Four-carbon skeletons:
Aspartate, asparagine Oxaloacetate
 Five-carbon skeletons:
Glutamine, glutamate, proline,
arginine, histidine Glutamate

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Three carbon skeletons
O O O

H2N CH C OH H2N CH C OH H2N CH C OH

CH3 CH2 CH2

OH SH

alanine serine cysteine

O O O
O O

H3C C C O- H3C C COO-

H3C C C OH

pyruvate

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Four carbon skeletons
O O

H2N CH C OH H2N CH C OH

CH2 CH2

C O C O

OH NH2

aspartate asparagine

COO- C OH

C O C O
or
CH2 CH2

COO- C O

OH

oxaloacetate

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Five-carbon skeletons
O
O
H2N CH C OH
C OH
CH2

CH2
HN
C O O

NH2 H2N CH C OH
proline
glutamine CH2

CH2

O C O O

H2N CH C OH OH H2N CH C OH

CH2 glutamate CH2

CH2
N
CH2
NH
NH

C NH

histidine
NH2

arginine

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 Glucogenic and Ketogenic Amino
Acids
Amino acids are classified as:
 Glucogenic if they generate pyruvate or

oxaloacete, which can be used to synthesize

glucose.
 Ketogenic if they generate acetoacetyl CoA or

acetyl CoA, which can form ketone bodies or

fatty acids.

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Ketogenic
Glucogenic

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 Sources of Amino Acids
 Essential amino acids must be obtained in the
diet.
 Nonessential amino acids are synthesized in
the body.

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 Synthesis of Amino Acids
 In humans, transamination of compounds from
glycolysis or the citric acid cycle produces
nonessential amino acids.

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 Essential Amino Acids
Essential amino acids are:
 Found in milk and eggs

(complete proteins).
 Not all found in grains and

vegetables
(incomplete proteins).
 Obtained by combining two

or more vegetables that

provide complementary
proteins.

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 Synthesis of Glutamine
 Glutamine is synthesized by adding another amino
group to glutamate.
NH3+ Glutamine
| synthetase
-OOC—CH—CH —CH —COO- + NH + ATP
2 2 3
Glutamate

NH3+ O
| ||
-OOC—CH—CH —CH —C—NH + ADP + P
2 2 2 i
Glutamine

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Disorders of AA metabolism
 Phenylketonuria
 Albinism
 Alkaptonuria
 type 1 tyrosinaemia
 nonketotic hyperglycinaemia
 Histidinaemia
 Homocystinuria
 maple syrup urine disease
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 Phenylketonurea (PKU)
In phenylketonurea (PKU):
 The gene that converts phenylalanine to tyrosine

is defective.
 Phenylalanine forms phenylpyruvate

(transamination), which goes to phenylacetate

(decarboxylation).
 High levels of phenylacetate cause severe mental

retardation.
 A diet low in phenylalanine and high in tyrosine

is recommended.

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Phenylketonurea (PKU)

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 Overview of Metabolism
In metabolism:
 Catabolic pathways degrade large molecules.

 Anabolic pathway synthesize molecules.

 Branch points determine which compounds are

degraded to acetyl CoA to meet energy needs or

converted to glycogen for storage.

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REFERENCES
1. Radwell VW. Metabolisme Protein dan Asam Amino. Dalam: Murray
RK, Granner DK, Rodwell VW. Biokimia Harper. Ed. 27. EGC. 2009:
250-89.
2. Poedjiadi A, Supriyanti T. Dasar-dasar Biokimia. UI Press. 2006: 297-
343
3. http://themedicalbiochemistrypage.org/home.html
4. http://www.runnersweb.com
5.
http://www.wiley.com/legacy/college/boyer/0470003790/animations/a
nimations.htm

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