Babylon Medical College

Clinical Biochemistry
Protein Digestion
Second stage Lectures 1
2022
Assistant. Prof D.Thana mohammed
E mail thanaswedi@yahoo.com
Digestion and Absorption Of
Proteins
 Protein
a class of nitrogenous organic
compounds which have large
molecules composed of one or
more long chains of amino acids
that consists of amino acid
residues joined by peptide bonds.
and are an essential part of all
living organisms, especially as
structural components of body
tissues such as muscle, hair, etc.,
and as enzymes and antibodies
Amino acid structure

• General structural
formula for α-amino
acids.
• There are 20 different
R groups in the
commonly occurring
amino acids.
 Amino acids are the building blocks of
proteins

• Structure of amino acid contain

Three major parts: carboxyl group,
amino group, and side chain.
• Central C atom called alpha
carbon.
• Amino acids can differ in their side
chains (R).
• The alpha carbon is a chiral center.
Classification of amino acid
Amino acids join together by forming
peptide bonds
The 20 amino acids
commonly found in
proteins are joined
together by peptide
bonds. Proteins are
chains of these peptide
units (polypeptides)
 Protien structure
Proteins do not exist as linear polypeptides
but rather fold to adopt a unique 3-
dimensional structure.
Protein structure is often discussed in
terms of a hierarchy
 Structure of proteins
• 1.Primary:simply the sequence of amino acids within the protein.
• 2.Secondary:folding of primary structure into a helical
arrangement or pleated sheets based on the sequence of amino
acids
• 3. Tertiary:is its complete three-dimensional conformation
• 4. Quarternary:
• refers to the association of two or more peptide chains in the
complete protein
Protein structure
 Biology/Chemistry of Protein Structure

Primary Assembly
STRUCTURE

PROCESS
Secondary
Folding

Tertiary
Packing

Quaternary
Interaction
 Biological Roles of Proteins
(examples
• ) 1. Catalysis (enzymes)
• 2. Transport (e.g., hemoglobin - O2 transport in blood; transport of ions
across cell membranes)
• 3. Storage (e.g., myoglobin - oxygen storage in muscle; Ferritin storage
of iron
• 4. Coordinated motion (e.g., in muscle like actine and myosin,)
• 5. Mechanical support (e.g., collagen)
• 6. Protection (e.g., immune system - antibodies; blood clotting
proteins)
• 7. Regulation and communication (e.g., hormones, receptors,)
Globular and Fibrous Proteins
• Globular Proteins
• Molecule forms a coiled shape
(globule)
• Hydrophobic amino acid located
inside centre of molecule away
from water
• Only hydrophilic amino acid are
exposed outside the molecule so
globular proteins are soluble
• Globular proteins have roles in
metabolic reactions:
– Enzymes - catalyse metabolic
reactions
– Haemoglobin - binds to
oxygen to transport it around
body
 Fibrous Proteins

• Polypeptides form long chains

running parallel to each other
• These chains are linked by
disulphide cross bridges – making
the proteins very stable and strong
• Fibrous proteins have Structural
functions:
– Keratin in skin and hair
– Collagen - found in bone,
cartilage, tendons and
ligaments for tensile strength
 Metabolism of protein
Metabolism consists of
anabolism (the buildup of
substances) and catabolism
(the breakdown of
substances). The term
metabolism is commonly
used to refer specifically to
the breakdown of food and
its transformation into
energy.
Dr.Saba 18
Amino acid catabolism is part of the larger process of the metabolism of
nitrogencontaining molecules. Nitrogen enters the body in a variety of
compounds present in food,the most important being amino acids
contained in dietary protein. Nitrogen leaves the
body as urea, ammonia, and other products derived from amino acid
metabolism.
Digestion of protein
• The dietary proteins are denatured on cooking and
• therefore more easily digested by enzyme called peptidase an
enzyme that hydrolyzes simple peptides these enzymes
• are hydrolases (class 3 enzymes) Depending on the source of
peptidases, the protein digestive process can be divided into 3
phases:
• 1-Gastric
• 2-Pancreatic
• 3-Intestinal
• Peptidase are Proteolytic enzymes are secreted as inactive form
called zymogens which are converted to their active form
• in the intestinal lumen. This would prevent autodigestion
• of the secretory acini.
• Protein digestion begins in the stomach.
• Entry of dietary protein into the stomach stimulates the
gastric mucosa to secrete gastrin which is a peptide
hormone primarily responsible secretion of hydrochloric
acid (HCl) into the stomach.
• HCI secreted by the parietal cells reduces the pH of
stomach to 1-2
• The acidic gastric juice is both an antiseptic agent, killing
most bacteria and other foreign cells, and a denaturating
agent, unfolding globular proteins.
Gastric Digestion of protein
Activation of pepsine
• Pepsin is an
endopeptidase,
Pepsin catalyses
hydrolysis of the
bonds formed by
• carboxyl groups of
Phe, Tyr, Trp and
Met.
 Pancreatic Digestion of
Proteins
• Pancreatic juice contains the important endopeptidases,namely Trypsin,
Chymotrypsin, Elastase and Carboxypeptidase.
• These enzymes are also secreted as zymogens
• (trypsinogen, chymotrypsinogen and pro-elastase),
• so that the pancreatic acinar cells are not autolysed.
• All the three are serine proteases, i.e.
• the active centers of these enzymes contain serine residues .The part
of the enzyme where the substrate binds is called the active site (since
that's where the catalytic “action” happens). A substrate enters the
active site of the enzyme.
• The optimum pH for the activity of pancreatic enzymes (pH 8) is provided by
the alkaline bile and pancreatic juice. The secretion of pancreatic juice is
• stimulated by the peptide hormones, Cholecystokinin
 Pancreatic Digestion of
Proteins
Exopeptidase: An enzyme
that catalyzes the cleavage
of the terminal (last) or next-
to-last peptide bond from a
polypeptide or protein,
releasing a single amino
acid or dipeptide. By
contrast, an endopeptidase
catalyzes the cleavage of
then internal peptide bonds
within a polypeptide or
protein
Action of protease
Endopeptidases (cleave
internal peptide bonds)
Exopeptidases
Carboxypeptidases
Aminopeptidases
Hormons regulation of protein digestion

• Secretin stimulates the pancreas to

secrete bicarbonate into the small intestine
to neutralize gastric HCI, abruptly
increasing pH to about 7.
• Gastric protein digests stimulate
cholecytokinin release in the duodenum,
triggering the release of main digestive
enzymes by the pancreas.
• Pancreatic proteases have different
substrate specificity with respect to
peptide bond cleavage.
• Trypsin arginine and Iysine residues
• Chymotrypsin aromatic amino acids
• Elastase hydrophobic amino acids
• The end products of this surface enzyme activity
are free amino acids, and di-and tripeptides
which are absorbed across the enterocyte
membrane by specific carrier-mediated
transport.
• Di-and tri-peptides are further hydrolyzed to their
constituent amino acids within the enterocyte.
• Final step is the transfer of amino acids out of
the enterocyte into portal blood.
• In humans, most globular proteins from
animal sources are almost completely
hydrolyzed to amino acids in the GI tract,
some fibrous proteins, such as keratin, are
only partly digested.
 Clinical significant
• Food Allergy
• Dipeptides and tripeptides can enter the brusborder of mucosal cells; they are
immediately hydrolysed into single amino acids. They are then
• transported into portal vein. Rarely, larger moleculesmay pass paracellularly
(between epithelial cells) and enter blood stream. These are immunogenic,
• causing antibody reaction, leading to food allergy.
• Celiac disease (celiac sprue) is a disease of malabsorption resulting from
• immune-mediated damage to the small intestine in response to ingestion of
• gluten (or gliadin produced from gluten), a protein found in wheatwheat, barley and
• rye.
• Abnrmalities in protein digestion: In individuals with a deficiency in pancreatic
• secretion (for example, due to chronic pancreatitis, cystic fibrosis, or surgical
• removal of the pancreas), the digestion and absorption of fat and protein are
• incomplete.
Review of protein metabolism
Transport summary

simple
diffusion
Passive transport

facilitated
diffusion

active ATP
transport
Transport of amino acid
• The absorption of amino acids
occurs mainly in
• the small intestine. It is an
energy requiring
• process. These transport
systems are carrier
• mediated and or ATP sodium
dependent symport
• systems.
There are different carriers for
amino acids:
1. Neutral amino acids (Alanine,
Valine, Leucine,Methionine,
Phenylalanine,Tyrosine,
Isoleucine)
2. Basic amino acids (Lys, Arg)
and Cysteine
3. Acidic amino acids (Asp, Glu)