Biochemistry

Seminar 1 Review
Nitrogen Metabolism
Alvin M. Tapia, MD, DPBO-HNS, FPSO-HNS
Department of Biochemistry
University of Perpetual Help Rizal JONELTA Foundation School of
Medicine

Digestion of Dietary
Protein
1. Digestion in the Stomach
2. Digestion by Pancreatic Enzymes
3. Digestion of Oligopeptides in the
small intestines

Digestion of Dietary
Protein
1. Digestion in the Stomach
a. Pepsin major proteolytic
enzyme
b. HCI cleaves pepsinogen to
pepsin

Digestion of Dietary
Protein
2. Digestion by Pancreatic Enzymes
a. Bicarbonate neutralizes stomach
acid
b. Endopeptidase
1.Trypsin
2.Chymotrypsin
3.Elastase

c.Exopeptidase
1.Carboxypeptidase A
2.Caboxypeptidase B

Digestion of Dietary
Protein
3. Digestion of Oligopeptides in
the small intestines
a. Aminopeptidase
b. Dipeptidase
c. Tripeptidase

Transport of Amino
Acids
1. Sodium-amino acid carrier
system
2. Gamma-glutamyl cycle
(pathway for synthesis and
degradation of glutathione and
drug and xenobiotic
detoxification)

Removal of Nitrogen
from Amino Acids
A. Transamination
Involves the transfer of an amino
group from one amino acid to an
alpha-keto group
Enzyme: Aminotransferase
Cofactor: Pyridoxal phosphate
B. Oxidative Deamination
Result in the liberation of the
amino group as free ammonia

1. Glucogenic Amino
Acids
Non-Essential

Essential

Alanine

Arginine*

Asparagine

Histidine

Aspartate

Methionine*

Cysteine

Threonine

Glutamate

Valine

Glycine

(Phenylalanine)*

Proline
Serine

2. Ketogenic Amino
Acids
a. Leucine
b. Lysine

3. Both Glucogenic and

Ketogenic Amino Acid
a.
b.
c.
d.
e.

Tyrosine
Isoleucine
Phenylalanine
Tryptophan
Threonine

Amino Acid Catabolism

What is the role of the urea
cycle in amino acid Breakdown?
It is the central pathway in nitrogen
metabolism. The urea cycle is a liver
resident process removing nitrogen
in form of ammonia to be excreted
from the body..

The Urea Cycle

The urea cycle consists of five reactions:
two mitochondrial and three cytosolic. The
mitochondrial matrix performs the biosynthetic
part of the precursors citrulline and aspartate,
and the cytoplasm (cytosol), which after
formation of arginino-succinate cleaves this
intermediate into three different products, one of
which is the net product (urea), the other two
(ornithine and fumarate) are recycled into the
matrix compartment and their respective cycle to
start a new round of urea formation.

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Urea Cycle
1. Carbamoyl Phosphate + Ornithine = Citrulline
2. Citrulline + Aspartate = Arginosuccinate
3.

Cleavage

of

Arginosuccinate

Arginine

&

Fumarate
4. Cleavage of Arginine Releases Urea & re-forms
Ornithine
5. Control of the Urea cycle Involves Carbamoyl
Phosphate Synthetase

Regulation of the
Urea Cycle
a. Arginine stimulates the synthesis of
N-acetyl glutamate
b. N-acetyl glutamate is an activator of
carbomoyl PO4 synthetase I
(mitochondrial enzyme involved in
production of urea)
c. High protein diet activates enzymes
of urea cycle

Degradation of
Amino Acids
1. Amino acids that are converted
to Pyruvate
a. Alanine
b. Serine
c. Glycine
d. Cysteine
e. Threonine

Degradation of
Amino Acids
2. Amino acids that can form
alpha-ketoglutarate
a. Glutamate
b. Proline
c. Arginine
d. Histidine

Degradation of
Amino Acids
3. Amino acids that can form
Succinyl CoA
a. Threonine
b. Methionine
c. Valine
d. Isoleucine

Degradation of
Amino Acids
4. Amino acids that can form
Fumarate
a. Phenylalanine
b. Tyrosine
c. Asparate

Degradation of
Amino Acids
5. Amino acids that can form Acetyl
CoA of Acetoacetate
a. Lysine
b. Threonine
c. Isoleucine
d. Phenylalanine
e. Tyrosine

Metabolism of
Ammonia
1. Sources of Ammonia
a. Amino acids
b. Glutamine
c. Bacterial action in the intestines
d. Amines
e. Purines and pyrimidines
2. Transport of Ammonia
a. Urea formation in the liver and
kidneys
b. Glutamine formation in muscle

Metabolism of
Ammonia
3. Hyperammonemia
Elevated concentration of
ammonia in the blood
Symptoms:
a.
b.
c.
d.

Tremors
Slurring of speech
Blurring of vision
Coma death

Metabolism of
Ammonia
4.Mechanism of Ammonia Toxicity
Increase in NH4 shift in the
equilibrium of glutamate dehydrogenase
reaction toward the direction of
glutamate formation:

alpha-ketoglutarate + NADPH + H+ NH3 glutamate +

NADP+

Catabolism of the
Carbon Skeletons of
Amino Acids

Involves the removal of alpha-amino

groups followed by the breakdown of the
resulting carbon skeletons forming 7
products:
1. Oxaloacetate
2. Alpha-ketoglutarate
3. Pyruvate
4. Fumarate
5. Acetyl CoA
6. Acetoacetyl CoA

THANK YOU!