protien digestion

digestion and absorption of proteins
proteins are large polypeptide molecules coiled by bonds in their tertiary structure, proteins are most important constituent of cell membranes and cytoplasm. muscle and blood plasma also contain certain specific proteins. protein is the most important biological molecules in building up and maintenances of the structure of body, giving as much energy as carbohydrates in the course of metabolism in the body. the digestion of proteins involves the gradual breakdown of this polypeptide by enzymatic hydrolysis in to amino acid molecules which are absorbed in the blood stream.
the protein load received by the gut is derived from two sources 70-100g dietary protein which is required daily and 35 -200g endogenous protein (secreted enzymes and proteins in the gut or from intestinal epithelia cell turnover)only 1-2g of nitrogen equivalent to 6-12g of proteins are lost in the feces on a daily basis.
digestion and absorption of proteins
proteins are large polypeptide molecules coiled by bonds in their tertiary structure, proteins are most important constituent of cell membranes and cytoplasm. muscle and blood plasma also contain certain specific proteins. protein is the most important biological molecules in building up and maintenances of the structure of body, giving as much energy as carbohydrates in the course of metabolism in the body. the digestion of proteins involves the gradual breakdown of this polypeptide by enzymatic hydrolysis in to amino acid molecules which are absorbed in the blood stream.
the protein load received by the gut is derived from two sources 70-100g dietary protein which is required daily and 35 -200g endogenous protein (secreted enzymes and proteins in the gut or from intestinal epithelia cell turnover)only 1-2g of nitrogen equivalent to 6-12g of proteins are lost in the feces on a daily basis.
proteolytic enzymes responsible for degrading proteins are produced by three different organs: the stomach, the pancreas, and the small intestine (figure 19.4).



the process of protein digestion can be divided, depending on the sources of peptidases.
a. gastric digestion
the digestion of proteins begins in the stomach, which secretes gastric juice a unique solution containing hydrochloric acid and the proenzyme, pepsinogen: entry of a protein in to stomach stimulates the gastric mucosa to secrete a hormone gastrin which in turn stimulates the secretion of hcl by the parietal cells of the gastric glands and pepsinogen by the chief cells.
the gastric digestion role are included the following
1. hydrochloric acid: stomach acid is too dilute ph 2 to 3) to hydrolyze proteins. the acid functions instead to kill some bacteria and to denature proteins, thus making them more susceptible to subsequent hydrolysis by proteases.
2. pepsin: this acid-stable endopeptidase is secreted by the serous cells of the stomach as an inactive zymogen (or proenzyme),
pepsinogen. in general, zymogens contain extra amino acids in their sequences, which prevent them from being catalytically active. [note: removal of these amino acids permits the proper folding required for an active enzyme.] pepsinogen is activated to pepsin, either by hci ,or autocatalytically by other pepsin molecules that have already been activated. this active pepsin cleaves the ingested protein at their amino terminus of aromatic amino acids (phe, tyr, and trp.) the major products of pepsin action are large peptide fragments and some free amino acids.

b. pancreatic digestion
pancreatic zymogens proceed digestion as the acidic stomach contents pass in to the small intestine, a low ph triggers the secretion of hormone secretin in the blood. secretin stimulates the pancreas to secrete hco-3 (bicarbonate), which in the small intestine neutralizes the gastric hcl and abruptly change the ph to 7.0.the entry of large peptide fragments and some free amino acids in the upper part of the small intestine (duodenum), excites the release of a hormone cholecytokinin (cck).cck function:
1) stimulates gall bladder contraction.
2) stimulate secretion of several pancreatic enzymes whose activity is between ph 7and 8 in proenzyme forms.
three of these pro-enzyme are trypsinogen, chymotrypsinogen and procarboxy peptidase, localized in the exocrine cells.synthesis of these enzymes as inactive precursors protects the exocrine cells from destructive proteolytic attack.when the proenzyme reach the lumen of the small intestine, initially the enteropeptidase (oldname enterokinase) a protease produced by duodenal epithelial cells, activates pancreatic trypsinogen to trypsin by the removal of a hexapeptide from nh2 – terminus trypsin in turn auto catalytically activates more trypsinogen to trypsin and other proenzymes and liberating chymotrypsin, elastas, and carboxypeptidase’s

by the sequential action of these proteolytic enzymes and peptides ingested proteins are hydrolyzed to yield a mixture of free amino acids which can be transported across the epithelial lining of the small intestine



table 5.4: digestive enzymes and their specificity

c. intestinal digestion
since pancreatic juice does not contain appreciable aminopeptidase activity final digestion of dia and oligopeptides depends on the small intestinal enzymes.
the lumenal surface of epithelial cells is rich in endopeptidase ,dipeptidase and aminopeptidase activity, the end products of the cell surface digestion are free amino acids and di and tripeptides.these are passed in to the interior of the epithelial cell where other specific peptidases convert almost all of them to a single amino acids that are transported to the blood stream by the opposite side of the cell membrane and carried to liver (primarily) and other tissues for oxidative degradation. this process complete the absorption of 99% of digested proteins. the whole scheme is as shown in the figure below.




ii. transport of amino acids in to intestinal epithelial cells.
the absorption of amino acids occurs mainly in the small intestine. it is active transport mechanism and energy requiring process. (for l-aas and dipeptides): there are mainly two mechanism
1- carrier protein transport system
( sodium – amino acid carrier system ).
2-h- depend trasport system
the mechanism of active transport of amino acids are similar with that of glucose uptake at the brush - border membrane the na+ - depend symporters a.as are absorbed by specific carrier protein in the cell membrane of the small intestinal cells.this carrier protein has one site for the a.a. and another site for the na+. it transports them from the intestinal lumen across the cell membrane to the cytoplasm. then the a.a. passes to the blood down its conc. gradient, while the na+ is pumped out from the cell to the intestinal lumen by na/k+ pump utilizing atp as a source of energy derived from na/k+ pump.
a similar h+ dependent symport is present on the brush border surface of di and tripeptides active transport in to the cell.
there are at least six specific symporter systems have been identified for the uptake of l-amino acids from the intestinal lumen.
1. neutral amino acid symporters with short or polar side chains.
ser, thr, ala,
2. neutral amino acid symporter for aromatic or hydropinghobic side chains.
phe, tyr,
3. lmino acid symporter pro,and oh – pro
4. basic amino acid symporter lys, arg and cys.
5. acidic amino acid symporter. asp, glu
6. ? amino acid symporter ?-ala,.
these transporter systems are also present in the renal tubules and defects in their constituent protein structure can lead to disease called hartnup disease( hartnup disease is an autosomal recessive disorder caused by the defective transport of amino acids in the small intestine and the kidneys).
intracellular protein degradation
protein degradation: all proteins in the body are constantly being degraded. half life(t 1/2) of a protein is the time taken to lower its concentration to half of the initial value. there are two major enzyme systems responsible for degrading damaged or unneeded proteins: the
1 -energy-dependent ubiquitin-proteasome mechanism,
2-the non-energy-dependent degradative enzymes of the lysosomes. proteasomes mainly degrade endogenous proteins, that is, proteins that were synthesized within the cell.
lysosomes primarily degrade extracellular proteins, such as plasma proteins that are taken into the cell by endocytosis, and cell-surface membrane proteins that are used in receptor-mediated endocytosis.
1. ubiquitin-proteasome proteolytic pathway: proteins destined for degradation by the ubiquitin-proteasome mechanism are first covalently attached to ubiquitin, a small, globular protein. ubiquitination of the target substrate occurs through linkage of the ?-carboxyl glycine of ubiquitin to a lysine e-amino group on the protein substrate. the consecutive addition of ubiquitinmoieties generates a polyubiquitin chain. proteins tagged with ubiquitin are then recognized by a large, barrel-shaped,proteolytic molecule called proteasome, a which functions like a garbage disposal (figure 19.3). the proteosome cuts the target protein into fragments that are then further degraded to amino acids, which enter the amino acid pool. degradation of proteins by the ubiquitinproteosome complex (unlike simple hydrolysis by proteolyticenzymes) requires atp, that is, it is energy-dependent.




b. chemical signals for protein degradation: because proteins have different half-lives, it is clear that protein degradation cannot be random, but rather is influenced by some structural aspect of the protein. for example, some proteins that have been chemically altered by oxidation or tagged with ubiquitin are preferentially degraded. the half-life of a protein is influenced by the nature of the n-terminal residue. for example ,proteins that have serine as the n-terminal amino acid are long-lived, with a half-life of more than twenty hours. contrast, proteins with aspartate as the n-terminal amino acid have a half-life of only three minutes.
nitrogen balance:
a healthy adult eating a varied and plentiful diet is generally in “normal nitrogen balance” a state where the amount of nitrogen ingested each day is balanced by the amount excreted resulting no net change in the amount of the body nitrogn and this occure in a well fed condition, excreted nitrogen comes from digestion of excess protein or from normal turnover protein turnover (synthesis and degradation) .under some conditions the nitrogen imbalances include is either in negative or positive nitrogen balance.
in negative nitrogen balance more nitrogen is excreted than ingested. this occurs in starvation and certain diseases.during starvation the carbon skeleton of most amino acids from proteins fed in to gluconeogenesis to maintain the blood glucose level in this process ammonia is released and excreted mostly as urea and is not reincorporated in to protein.
a diet deficient in an essential amino acid also leads to a negative nitrogen balance since body proteins are degraded to provide the deficient essential amino acid.

positive nitrogen balance occurs in pregnancy and during feeding after starvation and occurs in growing children who are increasing their body weight

amino acid pool and protein turnover.
amino acid catabolism is part of the larger process of whole body nitrogen metabolism. 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. the role of body proteins in these transformations involves two important concepts: the amino acid
pool and protein turnover.

a. amino acid pool
the entire collection of free amino acids in the body called amino acid pool.amino acids released by hydrolysis of dietary or tissue protein, or synthesized denova mix with other free amino acids distributed throughout the body. collectively, they constitute the amino acid pool (figure 19.2). the amino acid pool, containing about 100g of amino acids, is small in comparison with the amount of protein in the body (about 12kg in a 70 kg man).

b. protein turnover
protein turnover is the balance between protein synthesis and protein degradation.most proteins in the body are constantly being synthesized and then degraded, permitting the removal of abnormal or unneeded proteins. for many proteins, regulation of synthesis determines the concentration of protein in the cell .in healthy adults, the total amount of protein in the body remains constant, because the rate of protein synthesis is just sufficient to replace the protein that is degraded. the process, protein turnover, leads to the hydrolysis and resynthesis of 300 to 400 g of body protein each day. the rate of protein turnover varies widely for individual proteins. short-lived proteins (for example, many regulatory proteins and misfolding proteins) are rapidly degraded, having half-lives measured in minutes or hours. long-lived proteins, with half-lives of days to weeks, constitute the majority of proteins in the cell. structural proteins, such as collagen