Textbook - BIOLOGICAL CHEMISTRY - Hubsky Y.I. - 2000

Chapter VI. BIOCHEMISTRY OF PHYSIOLOGICAL FUNCTIONS AND SPECIALIZED TISSUES

CHAPTER 26. BIOCHEMISTRY OF HUMAN NUTRITION. I. NUTRITIONAL COMPONENTS. DIGESTION OF NUTRIENTS

26.3. MECHANISMS OF NUTRIENT TRANSFORMATION IN THE GASTROINTESTINAL TRACT

Nutrient Digestion (Proteins, CARBOHYDRATES, Lipids) is The process of Hydrolysis of respective compounds within food products that takes place in the alimentary canal, leading to The formation of simple Biomolecules that are absorbed into the bloodstream via specialized membrane transport mechanisms.

The initial processes of digestion occur in the Oral Cavity with the participation of saliva, a biological fluid with a pH of 6.8, which consists of 99.5 % Water and contains various proteins (Enzymes, mucins, IMMUNOGLOBULINS, Lysozyme, etc.) and inorganic salts. Saliva provides a lubricating effect on dry foods, facilitating the chewing process and creating conditions for the subsequent conversion of nutritional components under METABOLISM/18.html">The Influence of specific enzymes.

Salivary enzymes include glycosidases, which catalyze specific carbohydrate hydrolysis processes — specifically α-amylase and maltase. These enzymes can break down starch into high-molecular-weight dextrins and maltose into glucose; however, since the exposure time of saliva to the food bolus is brief, these products are formed in the oral cavity only in insignificant amounts.

The main processes of food nutrient digestion take place in The Stomach — where proteins are broken down into peptide molecules — and in various sections of the Small Intestine — where Peptides, carbohydrates, and fats (lipids) are hydrolyzed. The stomach produces its own Proteolytic Enzymes (pepsinogen, rennin); the intestine (Brunner's and Lieberkühn's glands) synthesizes certain peptidases, disaccharidases, phospholipases, and polynucleotidases. Intestinal digestion is impossible without the participation of hydrolytic enzymes delivered from the Pancreas — proteases (Trypsin, Chymotrypsin,

Elastase), carboxypeptidase, amylases, and lipases. The digestion of fats also involves BIOCHEMICAL COMPONENTS OF Bile synthesized in Liver hepatocytes.

Class="center">Protein Digestion

The biochemical processes of digestion of PROTEINS AND PEPTIDES entering The Human Body with food occur in the stomach and small intestine. The hydrolysis of these components proceeds under the action of enzymes produced by the Cells of the alimentary canal mucosa and the exocrine part of the pancreas. Proteases of the stomach, intestine, and pancreas hydrolyze specific peptide bonds in food proteins and peptides, and As a result of their sequential action, a mixture of free L-Amino Acids and simple peptides is formed, which are transported into enterocytes and subsequently into the bloodstream.

Protein Digestion in the Stomach

Gastric juice, which drives Protein Hydrolysis, is an acidic fluid with a pH of 1.5–2.5. The main biochemical components of gastric juice involved in The conversion of dietary proteins are Hydrochloric acid and the proteolytic enzyme Pepsin. In addition, gastric juice contains acid phosphates (primarily NaH₂PO₄) and certain organic acids, which constitute the total acidity of the stomach.

Hydrochloric acid is produced in specialized parietal (oxyntic) cells of the gastric mucosa using chlorides derived from the Blood. The donor of protons required for HCl formation is carbonic acid, produced from H₂O and CO₂ with the participation of Carbonic anhydrase:

The secretion of H⁺ ions into the gastric lumen occurs through the action of the proton pump in the membranes of oxyntic cells — the H⁺, K⁺-ATPase (Fig. 26.2).

Fig. 26.2. Scheme of hydrochloric acid production in the stomach, ~ H⁺, K⁺-ATPase.

The concentration of HCl in gastric juice ranges from 0.45 to 0.60 %. Hydrochloric acid is essential for the Formation of the active enzyme pepsin and the manifestation of its maximum catalytic activity.

Pepsin is a protease with a Molecular Weight of 42 kDa synthesized by the chief cells of the gastric mucosa as a proenzyme, pepsinogen (molecular weight 35 kDa). The Initial Stages of pepsinogen conversion into pepsin are mediated by H⁺ ions, which facilitate the Cleavage of the N-terminal protective peptide from the proenzyme molecule, accompanied by the exposure of the Active Site; subsequently, the process becomes autocatalytic, as pepsin molecules drive their own formation from the proenzyme:

By its MECHANISM OF ACTION, pepsin is an endopeptidase that specifically attacks peptide bonds formed by residues of aromatic (phenylalanine, Tyrosine) as well as dicarboxylic (glutamate, aspartate) amino acids. Under the action of pepsin, proteins are cleaved into large polypeptide fragments — peptones — the hydrolysis of which is completed in the small intestine.

Rennin (chymosin, rennet) is a protease found in the gastric juice of newborns. Rennin is an enzyme that, in the presence of Ca²⁺ ions, converts soluble milk proteins (caseins) into insoluble ones (paracaseins), which are then subjected to the proteolytic action of pepsin ("milk curdling");

Protein DIGESTION IN THE Intestine

The partially digested semi-liquid mass of nutrient compounds formed in the stomach (chyme) periodically passes through the pyloric sphincter into the duodenum. Proteolytic enzymes and peptidases from the pancreas are also delivered into this section of the alimentary canal to act on the peptides arriving from the stomach. The catalytic action of these enzymes takes place in a mildly alkaline environment (pH 7.5–8.0) established by sodium bicarbonate (NaHCO₃) present in intestinal juice.

Most proteolytic enzymes functioning in the small intestine are synthesized in the exocrine cells of the pancreas as proenzymes, which are activated upon entering the duodenum (trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidases A and B).

The Hydrolysis of Proteins and peptides derived from the stomach occurs both in the lumen of the small intestine and On the surface of enterocytes, known as parietal or membrane digestion.

Trypsin is a proteolytic enzyme with a molecular weight of 24.7 kD, formed in the intestinal lumen from the inactive proenzyme trypsinogen through the action of enterokinase, which cleaves the N-terminal hexapeptide from the proenzyme molecule to yield catalytically active trypsin:

Trypsin is an endopeptidase most active toward peptide bonds formed by the basic amino acids Arginine and Lysine.

Chymotrypsin is a proteolytic enzyme (MW 29 kD) generated from the proenzyme chymotrypsinogen through the catalytic action of trypsin, which cleaves several inhibitory peptides from the proenzyme molecule:

Chymotrypsin is an endopeptidase that cleaves up to 50% of peptide bonds in dietary protein and peptide molecules, including bonds insensitive to pepsin and trypsin.

Elastase is an endopeptidase that also exhibits broad substrate Specificity, cleaving peptide bonds formed by small amino acid residues such as Glycine, Alanine, and Serine.

The short peptides produced by the action of the aforementioned Endopeptidases are subjected to the action of intestinal exopeptidases—Carboxypeptidases A and B, aminopeptidases, and dipeptidases.

Carboxypeptidases are peptidases that hydrolyze peptide bonds formed by C-terminal amino acids: Carboxypeptidase A cleaves amino acids with hydrophobic radicals from the C-terminus, whereas carboxypeptidase B cleaves C-terminal lysine and arginine residues.

Aminopeptidases are enterocyte enzymes that cleave N-terminal amino acid residues from short peptides.

Dipeptidases are peptidohydrolases that break down dipeptides into free amino acids.

The sequential action of the entire set of gastric, pancreatic, and intestinal peptidohydrolases ensures the complete Digestion of dietary proteins and peptides down to amino acids. Only free Amino acids are absorbed into the bloodstream by the intestinal mucosa.

Carbohydrate Digestion

The primary carbohydrate breakdown reactions take place in the small intestine due to the action of pancreatic enzymes entering the duodenal lumen and intrinsic Enzymes of the intestinal juice. Similar to the Processing of proteins and peptides, alongside luminal digestion, carbohydrate digestion also occurs at the brush border (on The surface of enterocyte membranes) in the intestine.

Amylases acting in the intestine include α-amylase (predominantly) and β-amylase, which are synthesized in the pancreas. Pancreatic α-amylase is an endoglycosidase similar to salivary amylase, which hydrolyzes starch and Glycogen to yield a mixture of branched and unbranched Oligosaccharides along with some maltose and maltotriose. β-Amylase is a pancreatic exoglycosidase that cleaves maltose residues from unbranched homopolysaccharide chains. Hydrolysis of Homopolysaccharides at branching points (1→6) is catalyzed by α(1→6)-glucosidase.

Disaccharidases and oligosaccharidases are enzymes synthesized in the small intestine that catalyze The breakdown of respective sugars into Monosaccharides; these sugars are either produced by the action of amylases or enter the digestive tract as components of plant-based foods:

maltase (α-glucosidase) is an enzyme that hydrolyzes maltose and cleaves terminal glucose residues from the non-reducing ends of α(1→4)-linked oligosaccharides; maltase and isomaltase (α(1→6)-glucosidase) complete the degradation of homopolysaccharides initiated by amylases;

lactase (β-galactosidase) is an enzyme that breaks down lactose (milk sugar) into two monosaccharides—galactose and glucose; lactase is of paramount physiological importance in infant Nutrition;

sucrase (β-fructosidase) is an intestinal juice enzyme that hydrolyzes the disaccharide sucrose—the main component of beet and cane sugar—yielding glucose and fructose.

As a result of the action of these glycosidase enzymes on PLANT AND ANIMAL dietary carbohydrates, a mixture of monosaccharides is formed (mainly glucose, fructose, and galactose), which are absorbed by the intestinal epithelial cells and enter the blood. Glucose accounts for up to 90% of all blood monosaccharides, with the remainder consisting of other hexoses and pentoses, collectively forming the total blood sugar (4.5–6.5 mmol/L).

Disaccharidase Deficiency

There is a group of inherited enzymopathies associated with a deficiency in the Synthesis and Secretion into the intestinal juice of enzymes that hydrolyze Disaccharides. These enzymatic defects manifest as impaired DIGESTION AND ABSORPTION of the corresponding sugars.

Lactase Deficiency

A hereditary enzyme deficiency results in the inability of intestinal juice to break down milk sugar, a condition known as lactose intolerance.

In relatively rare cases, the pathology (congenital alactasia) manifests clinically during the very first days of a newborn's life when fed breast milk. However, in most cases, this enzymopathy presents as low lactase activity. This form of lactose intolerance is inherited as an autosomal recessive disorder and first appears during adolescence or early adulthood. The prevalence of lactase deficiency varies widely across different racial groups, being particularly common among populations in Eastern countries and people of color in North America. Specifically, the prevalence of this condition is 3 % among Danes and 97 % in Thais.

Sucrase deficiency is usually detected together with isomaltase deficiency as a combined defect—the intolerance of two disaccharides. This enzymopathy manifests after infants are transitioned to mixed feeding with The addition of fruit juices and other products containing plant sugars.

Clinically, disaccharidase deficiency manifests with symptoms of carbohydrate dyspepsia, such as diarrhea and meteorism; newborn infants fall behind in their development.

Fig. 26.3. Digestion of neutral fats by pancreatic lipase: TG - triacylglycerol; 1,2-DG - 1,2-diacylglycerol; 2-MG - 2-monoacylglycerol; FA - fatty acid.

Lipid Digestion

The digestion of dietary lipids takes place in the duodenum under the action of enzymes synthesized in an inactive form by the exocrine cells of the pancreas, namely lipase, phospholipase A₂, Cholesterol esterase, and endogenous intestinal enzymes.

1. Hydrolysis of neutral fats is driven by pancreatic lipase. Pancreatic lipase is specific to the ester bonds at the 1 and 3 positions of triacylglycerols, making free Fatty acids and 2-monoacylglycerol the products of this enzymatic action:

The optimal functioning of pancreatic lipase requires optimal alkalinity (pH of pancreatic secretion = 7.5–8.0) and the presence of amphipathic bile acid molecules (primarily glycocholic and taurocholic acids), which are essential for the emulsification of dietary fats and the formation of triacylglycerol micelles. The interaction between the lipase enzyme protein and the phase boundary in the bile salt/triacylglycerol system also requires an additional cofactor—colipase, a protein found in pancreatic secretion.

In addition to emulsifying dietary fats—a prerequisite for the action of pancreatic lipase—bile acids also participate in the formation and absorption of micellar structures (free fatty acids, monoglycerides) generated following the hydrolysis of triacylglycerols.

The bulk of bile acids (90–95 % of their total amount)

is absorbed into the blood via the portal vein in the lower sections of the small intestine and transported to the liver, where they are reused to form bile—a process known as enterohepatic Circulation. Thus, only up to 0.5 g of bile acids is excreted daily with feces; this loss is replenished through the synthesis of new primary bile acid molecules (cholic and chenodeoxycholic acids) from cholesterol in hepatocytes.

2. Hydrolysis of Phospholipids (Glycerophospholipids) is catalyzed by phospholipase A₂, which is synthesized in the pancreas as a proenzyme and converted into its active form through the tryptic hydrolysis of specific peptide bonds within the catalytically inactive protein molecule.

Pancreatic phospholipase A₂ hydrolyzes the ester bonds at position 2 of phosphoglycerides, yielding lysophospholipids. Other phospholipases present in intestinal juice break down glycerophospholipids into glycerol, Higher Fatty Acids, nitrogenous bases, and phosphoric acid:

Fig. 26.4. Scheme of glycerophospholipid molecule hydrolysis (X - nitrogenous base).

3. Hydrolysis of cholesterol esters occurs under the action of cholesterol esterase (cholesteryl ester hydrolase), yielding cholesterol, which is absorbed by enterocytes in its free form.

As a result of these biochemical processes affecting dietary lipids in the intestinal lumen, a complex mixture of products is formed, the Main Components of which are:

- free higher fatty acids (as Na⁺ and K⁺ salts);

- 2-monoacylglycerols;

- free (unesterified) cholesterol;

- glycerophospholipid hydrolysis products (glycerol, amino alcohols, phosphoric acid salts);

- triacylglycerols containing short-chain (primarily C₈-C₁₀) fatty acid residues. Such triacylglycerols make up to 10 % of the total neutral dietary fats; they can be absorbed by the epithelium of the small intestinal mucosa in an unhydrolyzed form \ and are cleaved into glycerol and fatty acids inside enterocytes.

Absorption of Lipid Digestion Products

The complex mixture of lipid hydrolysis products mentioned above forms lipid micelles that can be absorbed by the intestinal mucosa, and virtually all dietary fats enter the thoracic lymphatic duct through the absorption of these micelles. The penetration of lipid micelles into enterocytes occurs via pinocytosis or the diffusion of individual lipid molecules across the apical membrane of the cells.

Impaired Lipid Digestion Processes

Impaired hydrolysis and absorption of dietary lipids in the intestine lead to The Development of steatorrhea—the presence of an increased amount of fat in the feces.

The following types of disorders in human intestinal lipid digestion are distinguished (A.Sh. Byshevsky, O.A. Tersenov, 1994):

1) pancreatic lipase deficiency caused by pancreatic diseases—pancreatic steatorrhea;

2) bile deficiency in the intestine associated with liver or biliary tract diseases—hepatogenic steatorrhea;

3) inhibition of the enzyme systems responsible for lipolysis and triacylglycerol resynthesis in the intestine during intestinal diseases—enterogenic steatorrhea.