CHEM123
Ms. Rose Dyane F. Nunag, RMT, MPH
S.Y 2023- 2024: FINALS
LESSON 3: PROTEIN METABOLISM
PROTEIN DIGESTION & ABSORPTION
- Protein digestion (denaturation and hydrolysis)
starts in the stomach:
● Denatured by HCl in gastric juice (pH of
1.5-2.0)
● Enzyme pepsin hydrolyzes about 10%
peptide bonds
- Large polypeptide chains pass from stomach into
small intestine:
● pH in small intestine is 7.0- 8.0 and helps
neutralize the acidified gastric content
● Trypsin, chymotrypsin, and
carboxypeptidase in pancreatic juice
released into the small intestine help
hydrolyze proteins to smaller peptides.
● Aminopeptidase secreted by intestinal
mucosal membrane further hydrolyze the
small peptides to amino acids
● Amino acids (aa) liberated are
transported into blood stream via active
transport process
- The passage of polypeptides and small proteins
across the intestinal wall is uncommon in adults.
- In infants the transport of polypeptides allows the
passage of proteins such as antibodies in colostral
milk from a mother to a nursing infant to build up
immunologic protection in the infant
- Enzymes (Trypsin, chymotrypsin
carboxypeptidase, and aminopeptidase) are
produced in inactive forms called zymogens that
are activated at their site of action.
- Amino acids formed through digestion process
enters the amino acid pool in the body:
● Amino acid pool: the total supply of free
amino acids available for use in the human
body
- The amino acid pool is derived from 3 sources:
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1. Dietary protein
2. Protein turnover: a repetitive process in
which the body proteins are degraded and
resynthesized
3. Biosynthesis of amino acids in the liver
● Only non-essential amino acids
are synthesized
● 10 essential amino acids:
phenylalanine, valine, threonine,
tryptophan, isoleucine,
methionine, histidine, arginine,
lysine, and leucine
● Arginine and histidine are only
essential in infants
AMINO ACID UTILIZATION
NITROGEN BALANCE
- The state that results when the amount of
nitrogen taken into the human body as protein
equals the amount of nitrogen excreted from the
body in waste materials.
Two types of nitrogen imbalance can occur in
human body
1. Negative nitrogen imbalance: Protein degradation
exceeds protein synthesis
● Amount of N in urine exceeds nitrogen
consumed
● Results in tissue wasting
2. Positive nitrogen imbalance: rate of protein
synthesis (anabolism) is more than protein
degradation (catabolism)
● Results in large amounts of tissue
synthesis
● During growth, pregnancy, etc.
USES OF AMINO ACIDS
- Protein synthesis
● About 75% of amino acids go into
synthesis of proteins that is needed
continuous replacement of old tissues
(protein turnover) and to build new tissues
(growth).
- Synthesis of non- protein nitrogen-
containing compounds
● Synthesis of purines and pyrimidines for
nucleic acid synthesis
● Synthesis of heme for hemoglobin,
neurotransmitters, and hormones
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 - Synthesis of nonessential amino acids
● Essential amino acids can’t be synthesized
because of the lack of appropriate carbon
chain
- Production of energy
● Amino acids are not stored in the body, so
the excess is degraded
● Each amino acid has a different
mechanism of degradation
DEGRADATION PATHWAYS
- The amino nitrogen atom is removed and
converted to ammonium ion, which ultimately is
excreted from the body as urea.
- The remaining carbon skeleton is then converted
to pyruvate, acetyl CoA, or a citric acid cycle
intermediate, depending on its makeup, with the
resulting energy production or energy storage.
TRANSAMINATION AND OXIDATIVE DEAMINATION
Degradation of an amino acid takes place in two
stages
1. The removal of the -amino group
2. The degradation of the remaining carbon skeleton
Removal of amino group is a two- step process
- Transamination- biochemical process in which
the amino group of an alpha- amino acid is
transferred to an alpha- keto acid.
- Oxidative deamination- an amino acid is
converted into the corresponding keto acid by the
removal of the amine functional group as
ammonia and the ammonia eventually goes into
the urea cycle.
TRANSAMINATION
- Involves transfer of the amino group of an amino
acid to an alpha keto acid as shown in the reaction
below:
- Transamination is an enzyme catalyzed reactions
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- There are at least 50 transaminase enzymes
associated with transamination reactions
Initial effect of transamination
- Collect the amino groups from a variety of amino
acids into just two amino acids- glutamate (most
cells) and alanine (muscle cells)
● Net effect of transamination: Collection
of the amino groups from a variety of
amino acids into a single compound- the
amino acid glutamate
● To regenerate pyruvate and oxaloacetate
for use in further transamination reactions
OXIDATIVE DEAMINATION
- Ammonium ion (NH4+) group is liberated from the
glutamate amino acid formed from transamination
- Oxidative deamination reaction is a biochemical
reaction catalyzed by glutamate dehydrogenase in
which glutamate is converted into alpha-
ketoglutarate with the release of an ammonium
ion
- Occurs in liver and kidney
- The ammonium ion produced by oxidative
deamination is a toxic substance, so it is quickly
converted carbamoyl phosphate and then to urea
via the urea cycle mammals
- Two amino acids, serine, and threonine, undergo
direct deamination by dehydration- hydration
process rather than oxidative deamination
THE UREA CYCLE
- The net effect of amino acid degradation is the
production of ammonium ion which is toxic, and it
is converted to urea (relatively non- toxic
compound) in the liver via urea cycle.
- Urea cycle is a series of biochemical reactions in
which urea is produced from ammonium ions and
carbon dioxide.
- Urea is transported via the blood from the liver to
the kidneys and eliminated from the body via
urine.
Characteristics of Urea
● White solid
● Melting point 133oC
● Very soluble in water
● Odorless and colorless and has a salty taste
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CARBAMOYL PHOSPHATE
- The fuel for the urea cycle
- Two ATP molecules are expended in the formation
of one carbamoyl phosphate molecule
- A high energy phosphate bond is present in
carbamoyl phosphate
- It takes place in mitochondrial matrix
STEPS OF THE UREA CYCLE
Stage 1: Carbamoyl group transfer
- The carbamoyl group of carbamoyl phosphate is
transferred to ornithine to form citrulline
Step 2: Citrulline- aspartate condensation
- Citrulline is transported into the cytosol, citrulline
reacts with aspartate to produce argininosuccinate
utilizing ATP
- In this reaction the second of two nitrogen atoms
of urea is introduced into the cycle (one nitrogen
comes from carbamoyl phosphate and the other
from aspartate- original source of both is
glutamate)
Step 3: Argininosuccinate cleavage
- Argininosuccinate is cleaved to arginine and
fumarate by the enzyme argininosuccinate lyase
Stage 4: Hydrolysis of urea from arginine
- Hydrolysis of arginine produces urea and
regenerates ornithine- one of the cycle’s starting
materials
- The oxygen atom present in the urea comes from
water
- Ornithine is transported back to mitochondria to
be used in the urea cycle
UREA CYCLE NET REACTION
- Total of four ATP molecules is expended in the
production of one urea cycle molecule
● Two molecules are consumed in the
production of carbamoyl phosphate and
the equivalent of two ATP molecule is
consumed in step 2 of the urea cycle to
give AMP and two Pi
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LINKAGE BETWEEN THE UREA AND CITRIC ACID
CYCLES
- Fumarate produced is used in citric acid cycle
- Aspartate produced through transamination is
used in the urea cycle at step 2
AMINO ACID CARBON SKELETONS
- Transamination and oxidative deamination
produce an alpha- keto acid that contains the
carbon skeleton from the amino acid
- Each of 20 amino acids carbon skeletons undergo
a different degradation process
- Degraded products are pyruvate, acetyl CoA,
acetoacetyl CoA, alpha- ketoglutarate, succinyl
CoA, fumarate, and oxaloacetate
● Last four are intermediates in the citric
acid cycle
GLUCOGENIC AND KETOGENIC AMINO ACIDS
- Glucogenic Amino Acid
● The amino acids converted to citric acid
cycle intermediates can serve as glucose
precursors (glucogenic amino acids)
● An amino acid that has a carbon
containing degradation product that can
be used to produce glucose via
gluconeogenesis
- Ketogenic Amino Acid
● The amino acids converted to acetyl CoA
or acetoacetyl CoA can serve as fatty acids
and/or ketone body precursors (ketogenic
amino acids)
● An amino acid that has a carbon
containing degradation product that can
be used to produce ketone bodies
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FATES OF CARBON SKELETONS OF AMINO ACIDS
AMINO ACID BIOSYNTHESIS
- Non- essential amino acids are synthesized in 1-3
steps
- Essential amino acids are synthesized in 7-10
steps
- Excess amino acids are converted to fat and
stored
- Diet with lack of high- quality proteins results in
breakage of body proteins
Summary of the Starting Materials for the
Biosynthesis of the 11 Nonessential Amino Acids
HEMOGLOBIN CATABOLISM
- Red blood cells (RBCs) are highly specialized cells
whose primary function is to deliver oxygen to
cells and remove carbon dioxide from body tissues
- Mature red blood cells have no nucleus or DNA-
filled with red pigment hemoglobin
- Red blood cells are formed in the bone marrow
● ~200 billion new red blood cells are
formed daily
- The lifespan of a red blood cell is about 4 months
- Hemoglobin is a conjugated protein with two
parts:
● Protein portion is globin
● Prosthetic group is heme
- Iron atom interacts with oxygen forming a
reversible complex (oxygen can come on and off)
with it
- Old RBCs are broken down in the spleen (primary
site) and liver (secondary site)
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- Degradation of hemoglobin:
● Globin protein part is converted to amino
acids and are put in amino acid pool
● Fe atom becomes part of ferritin- an iron
storage protein- saves the iron for use in
biosynthesis of new hemoglobin molecules
● The heme (tetrapyrrole) is degraded to
bile pigments and eliminated in feces or
urine.
BILE PIGMENTS
- Bile pigments: The tetrapyrrole degradation
products secreted via the bile.
- There are four bile pigments:
● Biliverdin- green in color
● Bilirubin- reddish orange in color
● Stercobilin- brownish in color (gives
feces their characteristics brown color)
● Urobilin- yellow in color and present in
urine (gives characteristic yellow color to
urine).
- Daily normal excretion of bile pigments: 1-2mg in
urine and 250-350mg in feces.
- Jaundice: Results from liver, spleen, and
gallbladder malfunction.
● Results in higher than normal bilirubin
levels in blood and gives the skin and
white of the eye yellow tint.
INTERRELATIONSHIP AMONG METABOLIC
PATHWAY
- The metabolic pathways of carbohydrates, lipids,
and proteins are integrally linked to one another.
● A change in one pathway can affect many
other pathways.
- Examples:
● Feasting (overeating): Causes the body
to store a limited amount as glycogen and
the rest as fat.
● Fasting (no food ingestion): The body
uses its stored glycogen and fat for
energy.
● Starvation (not eating for a prolonged
period):
○ Glycogen stores are depleted
○ Body protein is broken down to
amino acids to synthesize glucose
○ Fats are converted to ketone
bodies
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