BIOCHEMISTRY FOR MEDICAL LABORATORY SCIENCE

SAMANTHA GRICEL L. MENDOZA | BSMLS 2-Y1-2 FINALS | LECTURE

TOPIC: PROTEIN METABOLISM

PROTEIN DIGESTION AND ABSORPTION

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 the stomach into

small intestine:
- pH in the small intestine is 7.0 -8.0 and helps
neutralize the acidified gastric content
- Trypsin, chymotrypsin, and carboxypeptidase in NITROGEN BALANCE
pancreatic juice released into the small intestine
help hydrolyze proteins to smaller peptides - The state that results when the amount of nitrogen
- Aminopeptidase secreted by intestinal mucosal taken into the human body as protein equals the
membrane further hydrolyze the small peptides to amount of nitrogen excreted from the body in waste
amino acids materials.
- Amino acids (aa) liberated are transported into
blood stream via active transport process TWO TYPES OF NITROGEN IMBALANCE

Negative nitrogen imbalance

- Protein degradation exceeds protein synthesis

- The passage of polypeptides and small proteins
- Amount of N in urine exceeds nitrogen consumed
across the intestinal wall is uncommon in adults.
results in tissue wasting
- In infants, the transport of polypeptides allows the
passage of proteins such as antibodies in colostrum
milk from a mother to a nursing infant to build up Positive nitrogen imbalance
immunologic protection in the infant. - Rate of protein synthesis (anabolism) is more than
- Enzymes (Trypsin, chymotrypsin carboxypeptidase, protein degradation (catabolism)
and aminopeptidase) are produced in inactive - Results in large amounts of tissue synthesis during
forms called zymogens that are activated at their growth, pregnancy, etc.
site of action.

AMINO ACID AMINO ACID UTILIZATION

PROTEIN SYNTHESIS
- Amino acids formed through the digestion process
enter the amino acid pool in the body - About 75% of amino acids go into the synthesis of
proteins that need continuous replacement of old
Amino acid pool tissues (protein turnover) and to build new tissues
- the total supply of free amino acids available for (growth).
use in the human body
SYNTHESIS OF NON-PROTEIN NITROGEN-CONTAINING
The amino acid pool is derived from 3 sources: COMPOUNDS

1. Dietary protein - Synthesis of purines and pyrimidines for nucleic

2. Protein turnover acid synthesis
- A repetitive process in which the body - Synthesis of heme for hemoglobin,
proteins are degraded and resynthesized neurotransmitters, and hormones
3. Biosynthesis of amino acids in the liver
- only non-essential amino acids are
synthesized
BIOCHEMISTRY FOR MEDICAL LABORATORY SCIENCE
SAMANTHA GRICEL L. MENDOZA | BSMLS 2-Y1-2 FINALS | LECTURE

SYNTHESIS OF NON-ESSENTIAL 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
INITIAL EFFECT OF TRANSAMINATION
-

AMINO ACID UTILIZATION: DEGRADATION PATHWAYS - Collect the amino groups from a variety of amino
acids into just two amino acids—glutamate (most
- The amino nitrogen atom is removed and converted cells) and alanine (muscle cells)
to ammonium ion, which ultimately is excreted from
the body as urea.
NET EFFECT OF TRANSAMINATION
- The remaining carbon skeleton is then converted to
pyruvate, acetyl CoA, or a citric acid cycle
- Collection of the amino groups from a variety of
intermediate, depending on its makeup, with the
amino acids into a single compound—the amino
resulting energy production or energy storage.
acid glutamate

TRANSAMINATION AND OXIDATIVE DEAMINATION - To regenerate pyruvate and oxaloacetate for use in
further transamination reactions
Degradation of an amino acid takes place in two stages:

1. The removal of the -amino group and

2. The degradation of the remaining carbon skeleton

Removal of amino group is a two step process:

1. Transamination - Ammonium ion (NH4+) group is liberated from the

- biochemical process in which the amino group of an
alpha-amino acid is transferred to an alpha-keto
acid.
2. 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.
glutamate amino acid formed from transamination
- Oxidative deamination reaction is a biochemical
reaction catalyzed by glutamate dehydrogenase in
which glutamate is converted into alpha-keto
glutarate with the release of an ammonium ion
- Occurs in liver and kidney

TRANSAMINATION

- Involves transfer of the amino group of an -amino

acid to an alpha keto acid as shown in the reaction
below:
- 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 in mammals
- Two amino acids, serine and threonine, undergo
- An enzyme catalyzed reactions
direct deamination by dehydration-hydration
- There are at least 50 transaminase enzymes
process rather than oxidative deamination
associated with transamination reactions
BIOCHEMISTRY FOR MEDICAL LABORATORY SCIENCE
SAMANTHA GRICEL L. MENDOZA | BSMLS 2-Y1-2 FINALS | LECTURE

UREA CYCLE STAGE 4: HYDROLYSIS OF UREA FROM ARGININE

- The net effect of amino acid degradation is the
production of ammonium ion which is toxic and it is
converted to urea (a relatively non-toxic
compound) in the liver via the 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.
- 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
- Orthinine is transported back to mitochondria to be
used in the urea cycle

Urea:
● white solid
● melting point 133oC
● very soluble in water
● odorless and colorless and has a salty
taste

CARBAMOYL PHOSPHATE

- The fuel for the urea cycle

- Two ATP molecules are expanded 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: CARBOMYL GROUP TRANSFER
- The carbamoyl group of carbamoyl phosphate is
transferred to ornithine to form citrulline
STAGE 2: CITRULLINE-ASPARTATE CONDENSATION
LINKAGE BETWEEN THE UREA AND CITRIC ACID CYCLES
- 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)
STAGE 3: ARGININOSUCCINATE CLEAVAGE
- Argininosuccinate is cleaved to arginine and
fumarate by the enzyme argininosuccinate lyase
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
- 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
produces 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 4 are
intermediates in the citric acid cycle
BIOCHEMISTRY FOR MEDICAL LABORATORY SCIENCE
SAMANTHA GRICEL L. MENDOZA | BSMLS 2-Y1-2
A. The amino acids converted to citric acid cycle
intermediates can serve as glucose precursors
(glucogenic amino acids).
Glucogenic amino acid
- An amino acid that has a carbon-containing
degradation product that can be used to produce
glucose via gluconeogenesis.
B. The amino acids converted to acetyl CoA or
acetoacetyl CoA can serve as fatty acids and/or
ketone body precursors (ketogenic amino acids)
Ketogenic amino acid
- An amino acid that has a carbon-containing
degradation product that can be used to produce
ketone bodies
FATES OF CARBON SKELETONS OF AMINO ACIDS
AMINO ACID BIOSYNTHESIS
FINALS | LECTURE
STARTING MATERIALS FOR THE BIOSYNTHESIS OF 11
NON-ESSENTIAL 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
- The life span of a red blood cell is about 4 months
- Red blood cells are formed in the bone marrow
- 200 billion new red blood cells are formed
daily
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
BIOCHEMISTRY FOR MEDICAL LABORATORY SCIENCE
SAMANTHA GRICEL L. MENDOZA | BSMLS 2-Y1-2 FINALS | LECTURE

- Old RBCs are broken down in the spleen (primary ➔ Body protein is broken down to
site) and liver (secondary site) amino acids to synthesize
glucose.
Degradation of hemoglobin ➔ Fats are converted to ketone
- Globin protein part is converted to amino acids and bodies.
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 pigm

BILE PIGMENTS

- The tetrapyrrole degradation products secreted via

the bile.

There are four bile pigments:

1. Biliverdin - green in color
2. Bilirubin - reddish orange in color.
3. Stercobilin – brownish in color (gives feces their
characteristic brown color).
4. Urobilin - yellow in color and present in urine
(gives characteristic yellow color to urine).

- Daily normal excretion of bile pigments: 1–2 mg in

urine and 250–350 mg in feces.

Jaundice: Results from liver, spleen and gallbladder

malfunction.
● Results in higher than normal bilirubin
levels in the blood and gives the skin and
white of the eye yellow tint.

INTERRELATIONSHIP AMONG METABOLIC PATHWAYS

- 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 (over eating): 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,