Digestion

The purpose of digestion is to hydrolyze proteins to small peptides and amino acids so that these can be absorbed. The daily protein load requiring digestion within the gastrointestinal tract includes both the exogenous protein derived from the food consumed and that from endogenous intestinal enzymes and cellular debris. The latter may constitute approximately 40% of the total gastrointestinal protein load, approximately 160-170 g. daily. The digestion of proteins in the gastrointestinal tract involves a coordinated series of events at different levels, with sequential digestion by proteolytic enzymes to a form that can be absorbed into the bloodstream. Figure 1 is a sequential representation of the various sites of protein digestion and absorption in the gastrointestinal tract. The main gastric and pancreatic proteolytic enzymes and their physiological functions are summarized in Table 1.

Stomach Peptic Activity

The digestion of proteins begins in the stomach by the actions of pepsins, which are secreted as the

Figure 1 Cascade of protein hydrolysis in the gastrointestinal tract.

precursor form pepsinogen by the gastric mucosa main cells. The release of pepsinogen is stimulated by gastrin, histamine, and cholinergic stimulation and sinogens are converted to the active form pepsin by the loss of a small basic peptide. Pepsins remain active in the acid pH of the stomach and have a broad proteolytic specificity, splitting peptide bonds mostly involving phenylalanine, tyrosine, and

Table 1 Proteolytic enzyme activity in the gastrointestinal tract

Enzyme

Precursor

Products

Catalyst

Substrate

Action

Stomach

Pepsins

Pepsinogens

Pancreatic proteases

Trypsin Trypsinogen

Chymotrypsin

Elastase

Carboxypeptidase A

Carboxypeptidase B

Chymotrypsinogen

Proelastase

Polypeptides of diverse sizes and some amino acids

Oligopeptides

Oligopeptides

Oligopeptides

Acid pH

Procarboxypeptidase A Aromatic amino acids and peptides

Procarboxypeptidase B Arginine, lysine, and peptides

Protein

Enterokinase Trypsin

Trypsin Trypsin

Trypsin

Trypsin

Proteins Polypeptides

Protein Polypeptides

Elastin

Other proteins

Polypeptides at the free C-terminal end of the chain

Polypeptides at the free C-terminal end of the chain

Hydrolyse bonds between aromatic amino acids (e.g., phenylalanine or amino acid)

Cleaves internal bonds at lysine or arginine amino acids; cleaves other pancreatic proenzymes Cleaves bonds of aromatic or neutral amino acids Cleaves bonds of aliphatic amono acids (e.g., alanine, glycine, and serine) Cleaves aromatic amino acids from C-terminal end of protein and peptides Cleaves arginine or lysine from C-terminal end of protein and peptides

Age (years)

Figure 2 Postnatal development of gastric acid secretion and titratable acidity. Modified from Koldovsky (1987). Digestion and absorption of carbohydrates, proteins and fat in infants and children. In Walker WA and Watkins JB (eds), Nutrition in Pediatrics, Boston, Little Brown. Reproduced with permission from Little Brown & Company.

Age (years)

Figure 2 Postnatal development of gastric acid secretion and titratable acidity. Modified from Koldovsky (1987). Digestion and absorption of carbohydrates, proteins and fat in infants and children. In Walker WA and Watkins JB (eds), Nutrition in Pediatrics, Boston, Little Brown. Reproduced with permission from Little Brown & Company.

leucine. The level of peptic activity and acid production is lower in premature infants and increases in relation to gestational age; pepsin activity increases approximately twofold between infancy and adulthood (Figure 2). Immunohistochemistry indicates two distinct forms of pepsinogen: Pepsinogen I is only found in acid-secreting regions of the stomach, whereas pepsinogen II is also found in the mucous cells of the oxynctic and pyloric regions of the stomach as well as in the duodenal Brunner's glands. Although these two forms of pepsinogen have slightly different pH optima, their substrate specificity is very similar and both are rapidly inactivated by the alkaline pH beyond the pylorus.

A gelatinase liquefying gelatin is also found in the stomach. There is controversy regarding the presence of rennin (a peptidyl peptide hydrolase) in the stomach of young infants; however, the mild clotting activity in human infants is fairly rapid.

The completeness of gastric protein digestion is dependent on several factors, including the rate of gastric emptying, the pH of intragastric contents, and the type of protein ingested. Given the significant buffering capacity of food, it is unlikely that gastric proteolysis plays a major role in protein digestion. This is also verified by the fact that neither patients with achlorhydria nor those recovering from major gastric surgery appear to have a major problem with protein digestion.

Pancreatic Proteases

The pancreatic proteases are secreted as proenzymes and are activated in the lumen. The enteropeptidase (also called enterokinase) released from the brush border membrane removes a hexapeptide from the N-terminal end of trypsinogen, converting it to the active form trypsin. Trypsin, in turn, activates the other protease proenzymes and also autocatalytically promotes further activation of trypsinogen. The pancreatic proteases include the endopeptidases trypsin, chymotrypsin, and elastase, primarily splitting peptide bonds located within the protein molecules resulting in the production of short-chain polypeptides. These are further hydrolyzed by the exopeptidases carboxypep-tidase A and B, acting on aromatic/aliphatic C terminals or basic C terminals, respectively, to remove single amino acids. The end product of this coordinated intraluminal digestion by these endopeptidases and exopeptidases is a mixture of neutral and basic amino acids (30%) with peptide chains varying in length from two to six amino acids (70%). The presence of excess amino acids in the lumen can further limit peptide hydrolysis (product inhibition).

The activity of enterokinase is noticeable after 26 weeks of gestation and its activity at term is approximately 10% of that of adults. Although pancreatic trypsin levels are substantial in both preterm and term infants, the secretory response to secretin and pancreozymin stimulation is somewhat blunted at birth compared with that at 2 years of age. However, such comparatively lower levels of protease activity in newborn infants do not appear to limit protein digestion significantly.

Brush Border Membrane and Cytoplasmic Peptidases

An important step in the final hydrolysis of peptides is their proteolysis to amino acids, either at the level of the intestinal brush border or within the cytoplasm of the intestinal mucosa. An important physiological observation is that protein absorption can occur both as amino acids and as peptides; indeed, absorption as peptides is considered a more efficient way of amino acid absorption compared with that of single amino acids (Figure 3). Even when a di- or tripeptide is subject to rapid hydrolysis by brush border peptidases, 30-50% of it is directly absorbed unconverted. The recognition that peptides are the main physiological routes of entry of amino acids into the enterocytes is a point of fundamental importance in the formulation of special protein hydroly-sates and enteral feeds.

A range of peptidases are present at the level of the brush border membrane or cytoplasm with the capability of hydrolyzing oligopeptides of up to eight amino acid residues (Table 2). These oligopep-tidases are synthesized in the rough endoplasmic reticulum of enterocytes and, after transfer through the Golgi apparatus, are transported to the brush border and extruded by exocytosis. There is little posttranslational processing of these peptidases, and they are attached to the brush border membrane by short anchoring pieces. The brush border pepti-dases differ in several ways from the cytoplasmic

Figure 3 Rates of glycine absorption (mean ± SEM) from perfusion solutions containing equivalent amounts of glycine in free or peptide form. (From Adibi SA, Morse EL, Masilamani SS and Amiu P (1975) Evidence from two different modes of tripeptide appearance in human intestine: Uptake by peptide carrier systems and hydrolysis by peptide hydrolases. Journal of Clinical Investigation 56: 1355-1363. Reproduced with permission from the American Society of Clinical Investigation.)

Figure 3 Rates of glycine absorption (mean ± SEM) from perfusion solutions containing equivalent amounts of glycine in free or peptide form. (From Adibi SA, Morse EL, Masilamani SS and Amiu P (1975) Evidence from two different modes of tripeptide appearance in human intestine: Uptake by peptide carrier systems and hydrolysis by peptide hydrolases. Journal of Clinical Investigation 56: 1355-1363. Reproduced with permission from the American Society of Clinical Investigation.)

peptidases; the bulk of the hydrolysis of tetrapep-tides and longer peptides occurs at the brush order, whereas the converse is true for dipeptidase activity, which is primarily within the cytoplasm. Most oligopeptidases are aminopeptidases, acting at the N-terminal amino acid. The brush border proteo-lysis rate is most rapid for tripeptides and least rapid for dipeptides, whereas the rates of hydrolysis of tetrapeptides and pentapeptides are somewhat intermediate. The brush border peptidases are capable of hydrolyzing all peptide bonds except those with praline at the C terminal.

In general, the cytoplasmic peptidases are more heat labile than brush border peptidases. Of the cytoplasmic peptidases, the most abundant is a dipeptidase that cleaves neutral dipeptides, whereas the aminotripeptidase has a high specificity toward tripeptides with N-terminal amino acids or those containing praline terminally.

Very little is known about the developmental aspects of brush border and cytoplasmic proteases. However, the activity of many of these proteases is discernible by 10-16 weeks of gestation and progressively increases during development. In contrast, 7-glutamyl transpeptidase activity decreases with increasing gestational age, but the significance of this transition is unknown.

Colonic Digestion

Although colonic digestion and fermentation is an important mechanism for energy production in plant-eating animals, its role in human nutrition is of minor importance. Colonic fermentation may lead to the production of short-chain fatty acids from undigested starch, nonstarch polysaccharides, or proteins reaching the colon, providing approximately 5-10% of daily energy requirements from this source. The contributory role of colonic protein digestion may become important for people with reduced small intestinal function such as short bowel syndrome.

Table 2 Peptidases present at the brush border membrane and cytoplasm of villous epithelial cells

Peptidase

Action

Products

Brush border membrane peptidase

Aminooligopeptidases (at least two

Cleave amino acids from C terminal of 3-8 amino acid

Amino acids dipeptides

types)

peptides

Aminopeptidase A

Cleaves dipeptides with acidic amino acids at N terminal

Amino acids

Aminopeptidase I

Cleaves dipeptides containing methionine

Amino acids

Aminopeptidase III

Cleaves glycine-containing dipeptides

Amino acids

Dipeptidyl aminopeptidase IV

Cleaves praline-containing peptides with free C terminal

Peptides and amino acids

Carboxypeptidase P

Cleaves praline-containing peptides with free C terminal

Peptides and amino acids

Angiotensin I converting enzyme

Cleaves 7-glutamyl bonds and transfers

7-Glut amino and/or

(ACE) 7-glutamyl transpeptidase

peptide

Endopeptidases (two, including PABA

peptidase)

Folate conjugase

Cleaves pteroyl polyglutamates

Monoglutamate

Cytoplasmic peptidases

Endopeptidases (several, including

Cleaves most dipeptides

Amino acids

Gly-Leu dipeptidase)

Aminotripeptidase

Cleaves tripeptides

Amino acids

Proline depeptidase

Cleaves X-Pro bonds in praline-containing depeptides

Proline and amino acids

PABA, para-aminobenzoic acid.

PABA, para-aminobenzoic acid.

30 Day Low Carb Diet Ketosis Plan

30 Day Low Carb Diet Ketosis Plan

An Open Letter To Anyone Who Wants To Lose Up To 20 Pounds In 30 Days The 'Low Carb' Way. 30-Day Low Carb Diet 'Ketosis Plan' has already helped scores of people lose their excess pounds and inches faster and easier than they ever thought possible. Why not find out what 30-Day Low Carb Diet 'Ketosis Plan' can do for you by trying it out for yourself.

Get My Free Ebook


Post a comment