книги студ / color atlas of physiology 5th ed[1]. (a. despopoulos et al, thieme 2003)

Digestion and Absorption of

Carbohydrates and Protein

!p. 22). The hydrolysis of saccharose, lactose, and trehalose is catalyzed by other brush border enzymes: lactase, saccharase (sucrase) and trehalase. In addition to glucose, these reactions release galactose (from lactose), which is absorbed by the same carriers as glucose, and fructose, which crosses the enterocytes by passive uniporters, GLUT5 in the luminal and GLUT2 in the basolateral membrane (!A2).

Lactase deficiency. Lactose cannot be broken down and absorbed unless sufficient lactase is available. Lactase deficiencies lead to diarrhea 1) because water is retained in the intestinal lumen due to osmotic mechanisms, and 2) because intestinal bacteria convert the lactose into toxic substances.

Protein digestion starts in the stomach (!B1). 258 HCl in the stomach denatures proteins and converts the three secreted pepsinogens into

about eight different pepsins. At a pH of 2–5, these endopeptidases split off proteins at sites where tyrosine or phenylalanine molecules are incorporated in the peptide chain. The pepsins become inactive in the small intestine (pH 7–8). Pancreatic juice also contains proenzymes of other peptidases that are activated in the duodenum (!p. 246). The endopeptidases trypsin, chymotrypsin and elastase hydrolyze the protein molecules into short-chain peptides. Carboxypeptidase A and B (from the pancreas) as well as dipeptidases and aminopeptidase (brush border enzymes) act on proteins at the end of the peptide chain, breaking them down into tripeptides, dipeptides, and (mostly) individual amino acids. These cleavage products are absorbed in the duodenum and jejunum.

Amino acids (AA) are transported by a number of specific carriers (!B2) similar to those found in the kidneys (!p. 158). Neutral (without net charge) and anionic (“acid”) L- amino acids are transported with Na+ symporters (secondary active transport; !p. 28) from the intestinal lumen into mucosal cells, from which they passively diffuse with carriers into the blood. Cationic (“basic”) L-amino acids such as L-arginine+, L-lysine+ and L-or- nithine+ are partly taken up into the enterocytes by Na+ independent mechanisms, as the membrane potential is a driving force for their uptake. Anionic amino acids like L-glutamate– and L-aspartate– which, for the most part, are broken down in the mucosal cells, also have their own (Na+ and K+ dependent) carrier systems. Neutral amino acids use several different transporters.

AA absorption disorders can be congenital and affect various amino acid groups. These disorders are often associated with defects of renal tubular reabsorption (renal aminoaciduria, e.g. cystinuria).

Dipeptides and tripeptides can be absorbed as intact molecules by a symport carrier (PepT1). The carrier is driven by an H+ gradient (!B2), which in turn is generated by H+ secretion (tertiary active H+-peptide symport, !p. 29 B5). Amino acids generally are much more rapidly absorbed as dipeptides and tripeptides than as free amino acids. Once they enter the cells, the peptides are hydrolyzed to free amino acids.

Vitamin Absorption

Since higher animals cannot synthesize cobalamins (vitamin B12), they must obtain this cobalt-containing coenzyme from the diet. Animal products (liver, kidneys, fish, eggs, milk) are the main source.

duodenum, resulting in the release of cobalamin, which is then bound by (trypsinresistant) intrinsic factor. The mucosa of the terminal ileum has highly specific receptors for the cobalamin-IF complex. IT binds to these receptors and is absorbed by receptor-mediated endocytosis, provided a pH of !5.6 and Ca2+ ions are available (!A2). The receptor density and, thus, the absorption rate increases during pregnancy. Cobalamin binds to TC I, II and III in plasma (!A3). TC II mainly distributes cobalamin to all cells undergoing division (TC II receptors, endocytosis). TC III (from granulocytes) transports excess cobalamin and unwanted cobalamin derivatives to the liver (TC III receptors), where it is either stored or excreted in the bile. TC I has a half-life of roughly 10 days and serves as a short-term depot for cobalamin in the plasma.

A vegan diet or disturbed cobalamin absorption can

260lead to severe deficiency symptoms like pernicious anemia and spinal cord damage (funicular myelosis).

It takes years for these symptoms to manifest as the body initially has a reserve of 1000 times the daily requirement of 1 µg (!p. 90).

Folic acid/folate (= pteroylglutamic acid). N5, N10-methylenetetrahydrofolate, the metabolically active form of folic acid (daily requirement: 0.1–0.2 mg) is needed for DNA synthesis (formation of deoxythymidylate from deoxyuridylate). Folic acid in the diet usually occurs in forms that contain up to seven glutamyl residues (γ-linked peptide chain; Pte-Glu7) instead of pteroylglutamic acid (Pte-Glu1). Since only Pte-Glu1 can be absorbed from the lumen of the proximal jejunum (!B), its polyglutamyl chain must be shortened before absorption. This is done by pteroylpolyglutamate hydrolases located in the luminal membrane of enterocytes. The absorption of Pte-Glu1 is mediated by a specific active transporter. In mucosal cells, Pte-Glu1 is than broken down to yield N5-methyltetrahydrofolate (5-Me-H4-fo- late) and other metabolites. If already present in the ingested food, these metabolites are absorbed from the intestinal lumen by the aforementioned mechanism. (The same applies to the cytostatic drug, methotrexate.) Methylcobalamin is needed to convert 5-Me-H4-folate to tetrahydrofolate (see above). The body stores about 7 mg of folic acid, enough for several months (cf. folic acid deficiency,

!p. 90).

The other water-soluble vitamins—B1 (thi-

amin), B2 (riboflavin), C (ascorbic acid), and H (biotin, niacin)—are absorbed via Na+ symport carriers (!C). Vitamin C is absorbed from the ileum, whereas vitamins B1, B2, and H are absorbed from the jejunum. Members of the vitamin B6 group (pyridoxal, pyridoxine, pyridoxamine) are probably absorbed by passive mechanisms.

Fat-soluble vitamins—A (retinol), D3

(cholecalciferol), E (tocopherol), K1 (phylloquinone), and K2 (menaquinone)—must be incorporated into micelles for absorption (cf. lipid digestion, p. 252). The exact absorption mechanism has not yet been explained, though it is known to be partly saturationand energy-dependent. Fat-soluble vitamins are incorporated into chylomicrons and VLDL for transport in plasma (!p. 254ff.).

C. Secondary active vitamin absorption

Water and Mineral Absorption

fluxes into cells of the duodenum and jejunum via symporter carriers, which actively cotransport glucose, amino acids, phosphates and other compounds (secondary active transport; !D1). Since this is an electrogenic transport mechanism (!p. 28), a lumen-negative transepithelial potential (LNTP; !p. 162) that drives Cl– out of the lumen forms (!D2).

Parallel transport of Na+ and Cl–: Na+ ions in the lumen of the ileum are exchanged for H+ ions (!D3) while Cl– is exchanged for HCO3– at the same time (!D4). The H+ ions combine with HCO3– to yield H2O + CO2, which diffuse out of the lumen. Most Na+, Cl– and, by sub-

Na+ diffusion: Na+ in the colon is mainly absorbed through luminal Na+ channels (!D5). This type of Na+ transport is electrogenic and aldosterone-dependent (!p. 182). The related lumen-negative transepithelial potential (LNTP, see above) either leads to K+ secretion or drives Cl– out of the lumen (!D2).

The Cl– secretion mechanism of epithelial cells (mainly Lieberkühn’s crypts, !p. 245, A16) is similar to that of the acini of salivary glands (!p. 236). The efflux of Cl– into the lumen and the associated efflux of Na+ and water are stimulated by cAMP and regulated by neurons and hormones such as VIP (vasoactive intestinal peptide) and prostaglandins. The physiological function of this form of H2O secretion could be to dilute viscous chyme or to ensure the recirculation of water (from the crypts !lumen !villi !crypts) to promote the absorption of poorly soluble substances. Cholera toxin inhibits the GTPase of the Gs proteins (!p. 274), thereby maintaining a maximal cAMP concentration and therefore a marked increase in Cl– secretion. In response to it, large quantities of water and Na+ are secreted into the lumen, which can lead to severe diarrhea (up to 1 L/hour!).

In addition to HCO3– from pancreatic juice, HCO3– is also secreted into the intestinal lumen by the small and large intestine (!A). K+ is secreted (aldosterone-dependent) by crypt cells of the colon (luminal K+ concentration !90 mmol/l!) and reabsorbed via the H+-K+ pump of the surface epithelium (similar to the mechanism in the stomach). The aldosteronedependent K+ secretion/absorption ratio determines the net amount of K+ excreted (!A and p. 180). Diarrhea results in losses of K+ and HCO3– (hypokalemia and metabolic acidosis; !p. 142).

Ca2+. The stool contains one-third of the dietary Ca2+ intake. Ca2+ is absorbed in the upper part of the small intestine (!A) with the aid of intracellular calcium-binding protein (CaBP). Calcitriol increases CaBP synthesis, thereby increasing Ca2+ absorption (!p. 292). Deficiencies of vitamin D or substances that form water-insoluble compounds with Ca2+ (phytin, oxalate, fatty acids) decrease Ca2+ absorption. Mg2+ is absorbed by similar mechanisms, but iron (Fe) is absorbed by a different mechanism (!p. 90).

B. Na+ and H2O absorption in the gut (model)

Plate 10.19

Integrative Systems of the Body

Hormones. Like neurotransmitters (see below) and the immune system’s cytokines and chemokines (!p. 94ff.), hormones serve as messenger substances that are mainly utilized for slower, long-term transmission of signals. Endocrine hormones are carried by the blood to target structures great distances away. Paracrine hormones (and other paracrine transmitters) only act on cells in the immediate vicinity of the cells from which they are released. Hormones that act on the cells that produced the messenger substance are referred to as autocrine hormones.

Hormones are synthesized in specialized glands, tissues and cells (e.g., neuroendocrine cells). Their target organ is either a subordinate endocrine gland (glandotropic hormone) or non-endocrine tissue (aglandotropic hormone). The target cells have high-affinity binding sites (receptors) for their specific hormone, so very low concentrations of the hormone suffice for signal transduction (10– 6 to 10– 12 mol/L). The receptors on the target cells pick out the substances specifically intended for them from a wide variety of different messenger substances in their environment.

Hormones work closely with the nervous system to regulate digestion, metabolism, growth, maturation, physical and mental development, maturation, reproduction, adaptation, and the internal milieu of the body (homeostasis) (!A). Most of these actions are predominately autonomous functions subject to central control by the hypothalamus, which is controlled by higher centers of the brain (!p. 330).

Neurotransmitters released at chemical synapses of nerve endings transmit signals to postsynaptic nerve fibers, muscles or glands (!p. 50ff.). Some neuropeptides released by presynaptic neurons also exert their effects in neighboring synapses, resulting in a kind of “paracrine” action.

Neurons can also secrete hormones, e.g., epinephrine, oxytocin and antidiuretic hormone. Some transmitter substances of the immune system, e.g. thymosin and various cytokines, also have endocrine effects.

Plate 11.1 Integrative Systems of the Body

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