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Dr. Walaa AL-Jedda – 2016/2017
Proteins are fundamental structural components of the body. They are "nitrogenous
macromolecules” composed of many amino acids.
Biomedical importance of proteins
1- Proteins are the main structural components of the cytoskeleton. They are the sole
source to replace Nitrogen of the body.
2- Biochemical catalysts known as enzymes are proteins.
3- Proteins known as immunoglobulin’s serve as the first line of defense against
bacterial and viral infections.
4- Several hormones are protein in nature.
5- Structural proteins furnish mechanical support and some of them like actin and
myosin are contractile proteins and help in the movement of muscle fiber,
microvillus…
6- Some proteins present in cell membrane, cytoplasm and nucleus of the cell act as
receptors.
7- The transport proteins carry out the function of transporting specific substances
either across the membrane or in the body fluids.
8- Storage proteins bind with specific substances and store them, e.g. iron is stored as
ferritin.
9- Few proteins are constituents of respiratory pigments and occur in electron
transport chain, e.g. cytochrome, hemoglobin, myoglobin.
10- Under certain conditions proteins can be catabolised to supply energy.
11- Proteins by means of exerting osmotic pressure help in maintenance of electrolyte
and water balance in body.
Dietary proteins: Proteins which we take in our diet are either from:
- animal source like milk and dairy products, meat, fish, liver, eggs.
- vegetable source like cereals, pulses, peas, beans and nut.
Digestion of proteins
-The (70- 100) g of protein consumed each day and an equal or larger amount of
protein that enters the digestive tract as digestive enzymes or in sloughed- off cells
from the intestinal epithelium are converted to amino acids by digestive enzymes.
- Many of the digestive proteases are produced and secreted as inactive zymogens.
They are converted to their active forms by removal of a peptide fragment in the
lumen of the digestive tract.
-Removal of these amino acids permits the proper folding required for an active
enzyme.
1- Digestion in the mouth: there are no proteolytic enzymes in mouth.
2- Digestion in the stomach: Gastric juice contains a number of proteolytic
enzymes, they are
*Pepsin is the major proteolytic enzyme. It cleaves proteins to smaller polypeptides.
. Pepsin is secreted as inactive zymogene form, pepsinogen. It is synthesized in
" chief cells" of stomach
HCl produced by the parietal cells of the stomach, HCl maintain the gastric pH at
about 1-2 and ensures maximum pepsin activity, causes a conformational changes in
pepsinogen that enables it to cleave itself (auto catalytically), forming pepsin.
Optimum pH for pepsin is 1.6-2.5, it gets denatured if pH is > 5.
Pepsin is a proteinase and it hydrolyzes peptide bonds inside the protein molecule
and produces proteoses and peptones.
Pepsin is active on peptide bond which connects to the carboxyl group of an
aromatic amino acids.
*Rennin is absent in adults, certain amount of rennin activity is seen in babies, in
infancy. It is secreted as prorennin, which is activated in the stomach to form active
rennin. Optimum pH for rennin is 4,and its action is similar to pepsin.
3- Digestion in the duodenum: Food 's bolus after leaving stomach reach
duodenum, where it meets with pancreatic secretions, which include bicarbonate and
a group of proteolytic enzymes.
A number of proteolytic enzymes are present in pancreatic juice to act on proteins and
partly digested products. Chief enzymes are:
(1) - Trypsin :is a proteinase secreted as an inactive zymogen form trypsinogen,
which is activated to form active Trypsin, which has strong proteolytic activity
- Trypsin acts in alkaline medium pH(8-9)( optimum pH 7.9).
Trypsin cleaves peptide bonds in which the carboxyl group is contributed by
arginine or lysine, and has many functions like:
(2) Chymotrypsin usually cleaves peptide bonds in which the carboxyl group is
contributed by the aromatic amino acids or by leucine.
-Chymotrypsinogen, the inactive zymogene, is cleaved to form Chymotrypsin by
Trypsin.
α-Chymotrypsin is the active form, optimum pH(7-8), it converts the proteoses,
peptones and peptides to smaller peptides and amino acids.
(3)- Elastase : has maximum activity on peptide bonds connected to carbonyl groups
of neutral aliphatic amino acids.
- Proelastase, the inactive zymogene is cleaved to elastase by trypsin.
(4)- Collagenase: it act on proteins present in collagen.
(5)- Carboxy peptidase: Two types of carboxy peptidase A and B.
The carboxy peptidases are produced as procarboxy peptidases, which are cleaved to
the active form by trypsin. Carboxypeptidases A and B cleave one amino acid at a
time from the C-terminal end of peptide.
- Carboxypeptidase A:a metallo-enzyme contain Zn, it is an exopeptidase that
cleaves aromatic amino acids from the C-terminal end of peptides.
Carboxypeptidase B : is also an exopeptidase cleaves the basic amino acids, lysine
and arginine, from the C- terminal end of peptides.
Both enzymes are ineffective in hydrolyzing dipeptides, with optimum pH(7.5).
4- Digestion in small intestine: proteolytic enzymes present in intestinal juice are:
1- Enterokinase: also known as enteropeptidase. A glycoprotein enzyme.
2- Amino peptidase: can hydrolyze peptides to tripeptides, but can't hydrolyze
a dipeptide, it requires presence of Zn++,Mn++ and Mg++.
Amino peptidase can hydrolyze a terminal peptide bond from the N-terminal
end, so split off the end a. a.
3- Prolidase: an exopeptidase and can hydrolyze a proline peptide of collagen
molecule, liberating a proline molecule.
4- Tri and Di-peptidases: they requires the presence of Zn++, Mn++ and Co++
as cofactors for their activity.
- Tri-peptidase acts on tri-peptide and produces a di-peptide and free a. a.
-Di-peptidase hydrolyzes a di-peptide to produce two molecules of a. a.
- Only free amino acids are found in the portal vein after a meal containing protein.
- These amino acids are either metabolized by the liver or released in the general
circulation.
*Abnormalities in protein digestion: due to a deficiency in
pancreatic secretion for example due to chronic pancreatitis, cystic fibrosis or
surgical removal of the pancreas leading to incomplete digestion and absorption
of fat and protein that result in abnormal appearance of lipid (steatorrhea) and
indigestible protein in the feces.
Transport of amino acids
The concentration of free amino acids in the extracellular fluids is significantly
lower than within the cells of the body. This concentration gradient is maintained
because active transport system derived by the hydrolysis of ATP, are required for
the movement of amino acid from the extracellular space into cell.
-L-amino acids are absorbed (by active transport process) more rapidly than Damino acid which absorbed slowly by simple passive diffusion.
-Amino acids are absorbed by intestinal epithelial cells and released into the blood by
two types of transport systems.
- At least seven different carrier proteins are known, that have overlapping specificities
for transport different groups of amino acids.
1. Sodium- amino acid carrier system
-The major transport system involves the uptake by the cell of a sodium ion and an
amino acid by the same carrier protein on the luminal surface.
-The sodium ion is pumped from the cell into the blood by the Na+- K+ ATPase, while
the amino acid travels down its concentration gradient into the blood.
- Thus, the transport of amino acids from the intestinal lumen to the blood is driven by
the hydrolysis of ATP.
2. - Glutamyl cycle
- An amino acid in the lumen reacts with tri-peptide glutathione (- Glutamylcysteinyl- Glycine) in the cell membrane, forming a - glutamyl amino acid and the
dipeptide cysteinyl-glycine
- The amino acid is carried across the membrane attached to - glutamate and released
into the cytoplasm. The - glutamyl moiety is used in the resynthesis of glutathione.
-The transport of one molecule of amino acid requires 3 molecules of ATP.