PROTEIN

METABOLISM
Stoker Chapter 26
Lippincott Chapter 19 and 20

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• Protein digestion starts in the stomach
• Dietary protein present in the stomach stimulates the release
of gastrin
• Gastrin promotes secretion of pepsinogen and HCl
• HCl in the stomach has 3 functions
• Antiseptic properties kill most bacteria
• Denaturing action “unwinds” globular properties
• Acidic property leads to activation of pepsinogen
• Pepsin affects the hydrolysis of 10% peptide bonds

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 Production of secretin is stimulated by
the passage of small amounts of acidic
protein content into the small intestine
Secretin stimulates bicarbonate (HCO3-) production,
which in turn helps neutralize acidified gastric content
• Promotes secretion of pancreatic digestive enzymes trypsin,
chymotrypsin, and carboxypeptidase in their inactive forms

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 PROTEIN DIGESTIVE ENZYMES
IN THE INTESTINE
• Proteolytic enzymes
• Enzymes that attack peptide bonds
• Pepsin
• Trypsin
• Chymotrypsin

• Zymogens
• Proteolytic enzymes produced in inactive form

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• Liberated amino acids are transported into the bloodstream 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 colostrum milk
from a mother to a nursing infant to build up
immunologic protection in the infant

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 FIGURE 26.1 - DIGESTION OF
PROTEIN IN HUMANS

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 AMINO ACID POOL

• Amino acids formed through digestion process enter the amino

acid pool in the body
• Amino acid pool: The total supply of free amino acids available
for use in the human body
• Sources
• Dietary protein
• Protein turnover: The repetitive process in which proteins
are degraded and resynthesized
• Biosynthesis of amino acids in the liver
• Only nonessential amino acids are synthesized
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 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
• Types of nitrogen imbalance
• Negative nitrogen imbalance - Protein degradation exceeds
protein synthesis
• Amount of nitrogen in urine exceeds consumed amount
• Results in tissue wasting
• Positive nitrogen imbalance - Rate of protein synthesis
(anabolism) is more than protein degradation (catabolism)
• Indicated by the synthesis of large amounts of tissue
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USES OF AMINO ACIDS IN
THE HUMAN BODY
• Protein synthesis
• Uses approximately 75% of free amino acids
• Synthesis of non-protein nitrogen-containing compounds
• Synthesis of purines and pyrimidines
• Synthesis of heme for hemoglobin
• Synthesis of nonessential amino acids
• Essential amino acids cannot be synthesized due to the lack of an
appropriate carbon chain
• Production of energy
• Amino acids are not stored in the body
• Excesses are degraded
• Each amino acid has a unique degradation pathway

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DEGRADATION PATHWAYS

• The amino nitrogen atom is removed

and excreted from the body as urea
• The remaining carbon skeleton is
converted to pyruvate, acetyl CoA, or a
citric acid cycle intermediate

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• Degradation of an amino acid takes place in two stages
̶ Removal of the α-amino group
̶ Degradation of the remaining carbon skeleton
• Removal of amino groups requires:
• Transamination: A biochemical reaction characterized by
the interchange of the amino group in an α-amino acid with
the keto group in an α-keto acid
• Oxidative deamination

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 GLUTAMATE PRODUCTION
VIA TRANSAMINATION
Glutamate is produced through transamination when α-ketoglutarate is the amino
group acceptor

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 ASPARTATE PRODUCTION VIA
TRANSAMINATION
This occurs when glutamate is the reacting acid and oxaloacetate is the reacting
keto acid
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 AMMONIUM PRODUCTION VIA
OXIDATIVE DEAMINATION
• Oxidative deamination is a biochemical reaction in which an α-
amino acid is converted to an α-keto acid with release of an
ammonium ion
• Occurs in the mitochondria of the liver and kidney

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 They undergo direct
deamination by a
dehydration–hydration
process rather than
oxidative deamination.
SERINE AND
THREONINE This different behavior
results from the presence
of a side-chain b-hydroxyl
group, a feature unique to
these two acids

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 • The net effect of transamination and deamination reactions is the
production of ammonium ions and aspartate
• Urea cycle: A series of biochemical reactions in which urea is
produced from ammonium ions and aspartate as nitrogen sources
• Urea produced in the liver is transported via blood to the kidneys
and eliminated from the body in urine
• Urea is an odorless white solid with a salty taste, has a melting
point of 133oC, and is soluble in water

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 INTERMEDIATES
arginine, ornithine, and citrulline

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 One of the sources of fuel for the
urea cycle

Two ATP molecules are

expended in the formation of one
carbamoyl phosphate molecule
CARBAMOYL
PHOSPHATE
It contains a high-energy
phosphate bond

It is formed in the mitochondrial

matrix

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 Stage Carbamoyl group transfer
1 • The carbamoyl group of carbamoyl
phosphate is transferred to ornithine
to form citrulline

STEPS OF
Stage Citrulline–aspartate condensation
THE UREA 2
• Citrulline is transported into the cytosol and
reacts with aspartate to produce

CYCLE argininosuccinate synthetase, utilizing ATP

Stage Argininosuccinate cleavage

• Argininosuccinate is cleaved to arginine
3 and fumarate by the enzyme
argininosuccinate lyase

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 STEPS OF THE
UREA CYCLE
• Stage 4 - Urea from arginine
hydrolysis
• Hydrolysis of arginine produces
urea and regenerates ornithine
under the influence of arginase
• The oxygen atom present in urea
comes from water
• Ornithine is transported back to
mitochondria to be used in the urea
cycle

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 UREA CYCLE NET
REACTION
• The equivalent of four ATP molecules
is expended in the production of one
urea molecule
• Two molecules of ATP are
consumed in the production of
carbamoyl phosphate
• The equivalent of two ATP
molecules is consumed in step two
of the urea cycle to give AMP and
the PPi

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 FIGURE 26.6 - CONVERSION OF
CARBAMOYL PHOSPHATE TO UREA

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 LINKAGE BETWEEN THE UREA AND
CITRIC ACID CYCLES
• Fumarate produced is ultimately converted to asparte
• Aspartate re-enters the urea cycle at step two

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 OXALOACETATE
PRODUCED FROM
FUMARATE
• can be:
• (1) converted to glucose via
gluconeogenesis
• (2) condensed with acetyl CoA to form
citrate
• (3) converted to pyruvate.

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 UREA CYCLE INTERMEDIATES
AND NO PRODUCTION

• Arginine and citrulline:

production of the biochemical
messenger molecule nitric
oxide, NO

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• Transamination/oxidative deamination removes the amino group from
an amino acid
• An α-keto acid that contains the skeleton of the amino acid is
produced
• Each of the 20 amino acids undergo a different degradation process
• Products formed are among a group of seven intermediates
• Four products are intermediates in the citric acid cycle
• Three products are pyruvate, acetyl CoA, and acetoacetyl CoA

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• The amino acids converted to citric acid cycle intermediates can serve
as glucose precursors
• Glucogenic amino acid: An amino acid that has a carbon-
containing degradation product that can be used to produce
glucose via gluconeogenesis
• The amino acids converted to acetyl CoA or acetoacetyl CoA can
contribute to the formation of fatty acids
• Ketogenic amino acid: An amino acid that has a carbon-
containing degradation product that can be used to produce
ketone bodies

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FIGURE 26.9 - FATES OF CARBON
SKELETONS OF AMINO ACIDS

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 Nonessential amino
acids are synthesized
in fewer steps than
essential amino acids

The primary source

of essential amino
acids for humans and
animals is plants

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 FIGURE 26.10 - SUMMARY OF THE STARTING MATERIALS
FOR THE BIOSYNTHESIS OF THE 11 NONESSENTIAL
AMINO ACIDS

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• They 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 hemoglobin
• Red blood cells are formed in the bone marrow
• Approximately 200 billion new red blood cells are
formed daily
• The life span of a red blood cell is approximately four
months

RED BLOOD CELLS

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 Hemoglobin is a
conjugated protein
with two components
• Globin - The protein portion
• Heme - The prosthetic group

Iron atom present in

heme interacts with
oxygen

A reversible complex is
formed

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• Old RBCs are broken down in the spleen and liver
• Degradation of hemoglobin
• Globin protein part is converted to amino acids, which
become part of the amino acid pool
• The iron atom becomes part of ferritin
• An iron-storage protein
• The tetrapyrrole carbon arrangement of heme is degraded to
bile pigments
• Eliminated in feces or urine

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 • Colored tetrapyrrole
degradation products
present in bile
• Types of bile pigments
BILE • Biliverdin - Green in color
PIGMENTS
• Bilirubin - Reddish orange in
color
• Stercobilin - Brownish in
color
• Urobilin - Yellow in color

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 • Daily normal excretion of
bile pigments
• 1–2 mg in urine
• 250–350 mg in feces
BILE
• Jaundice
PIGMENTS
• Caused by an imbalance
between the formation and
removal of bilirubin
• Gives the skin and white of
the eye the characteristic
yellow tint of the illness
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 BIODEGRADATION OF CYSTEINE

• Occurs in two steps

• A transamination reaction
• Release of —SH

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 BIOSYNTHESIS OF CYSTEINE
Serine is the precursor

Serine is converted to cysteine in two steps

• Activation of serine by an acetyl CoA molecule
• Sulfhydration with hydrogen sulphide
• Hydrogen sulphide is produced by sulfate
assimilation

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 FIGURE 26.13 (A) - STEPS 1 AND
2 OF SULFATE ASSIMILATION

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 FIGURE 26.13
(B) - STEPS 3
AND 4 OF
SULFATE
ASSIMILATION

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 HYDROGEN SULFIDE AS A
BIOCHEMICAL SIGNALLING AGENT

• It regulates vascular blood flow and blood

pressure
• Acts as a smooth muscle relaxant and vasodilator

• It influences brain function

• Brain levels of H2S are lower than normal in cases of
Alzheimer’s disease

• It influences insulin levels in type I diabetes

• Excess of H2S leads to reduced insulin production
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• 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 - Food is not ingested
− The body uses its stored glycogen and fat for
energy
− Starvation - Prolonged fasting
− Body protein is broken down to amino acids to
synthesize glucose

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• All eight B vitamins participate in
various pathways of protein
metabolism
• Niacin
• Oxidative deamination reactions
• PLP
• Transamination reactions

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FIGURE 26.15 - INVOLVEMENT OF B
VITAMINS IN PROTEIN
METABOLISM

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