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Neural and Neuroendocrine Control of Digestion: Regulation of Gastrointestinal Hormone Secretion

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Neural and Neuroendocrine Control of Digestion: Regulation of Gastrointestinal Hormone Secretion Neural and Neuroendocrine Control of Digestion: Regulation of Gastrointestinal Hormone Secretion (Chapter 15 in “Eckert Animal Physiology) (Chapter 4 in Hill, Wise & Anderson: “Animal Physiology”) (Chapter 10 in Hadley: “Endocrinology”) General Concepts Covered: — neural and neuroendocrine integration of a complex physiological process — co-ordination of endocrine and exocrine secretion — exocrine secretion affecting endocrine status — endocrine influences on neural, muscle and secretory functions — paracrine and autocrine effects — local influences — positive and negative “feed-back” actions — enzymatic cascades — integration of carbohydrate, fat and protein digestion and appetite control General Introduction — digestion requires co-ordination of movement of food particles, mechanical and chemical digestion of food — opening and closing of sphincter muscles to contain food particles in certain gut compartments for appropriate processing, also control passage through compartments — proper sequential enzymatic processing General Introduction (cont.) — peristaltic action to move food through gut — kneading movement to mix food particles with enzymes and to expose new surfaces for digestion, as well as for absorption From Eckert Secretin - first proposed hormone — 1902, WM Baylist and EH Starling (observations in dogs) — addition of food or acid in stomach is usually followed by pancreatic enzyme secretion into intestine — dennervate and tie off duodenum from stomach, then 1) add acid to stomach - no pancreatic enzyme secretion 2) add acid to blood - no pancreatic enzyme secretion 3) add partly digested food from stomach to duodenum - pancreatic enzyme secretion 4) add acid to duodenum - pancreatic enzyme secretion 5) tie off blood supply to and from duodenum and add acid to duodenum - no pancreatic enzyme secretion — hypothesis: duodenum exposed to acid from stomach releases a blood-borne factor to cause pancreatic enzyme secretion Secretin - first proposed hormone (continues) — scrap off mucosal layer of duodenum (i.e., preparation of epithelial cells of the duodenum) add acid — extraction of soluble products secreted from the resulting mixture — inject crude purified material into blood-stream of an animal under controlled conditions - pancreatic enzyme secretion — conclusion: hormone released from duodenum to stimulate pancreatic enzyme secretion — hormone named SECRETIN Quick Review of Enzymatic Digestion - General — enzymatic digestion usually involves hydrolysis of chemical bonds, separation of building units of the substrate, and the release of energy — some enzymes are very specific, acting on a limited range of substrates; others may be less specific — different conditions (e.g., pH) required for different enzymatic steps — many of these enzymatic steps in digestion take place extracellularly so that bigger molecules are broken down to small units that can be absorbed by the epithelial cells lining the gut — once absorbed, final metabolic processing can occur intracellularly Quick Review of Enzymatic Digestion – Carbohydrate 1 — carbohydrates are sugar molecules — complex polysaccharides digested by polysaccharidase; e.g., amylase in saliva and pancreatic secretions breaks down plant and animal carbohydrates (starch and glycogen) into disaccharides (e.g., maltose, sucrose and lactose) From Eckert Quick Review of Enzymatic Digestion – Carbohydrate 2 — maltase, sucrase and lactase in small intestine further reduces these disaccharides to monosaccharides — monosaccharides (pentose and hexose) can then be absorbed by the gut epithelium via carrier mediated transport systems From Hill et al. Mouth Stomach Intestine From “Principles of Animal Physiology” by Moyes & Schulte, 2nd edition Intestinal villi structure increases surface area for absorption GLUT = glucose transporter SGLT = sodium-glucose transporter From Hill et al. Quick Review of Enzymatic Digestion – Carbohydrate 3 — other structural carbohydrates require other considerations — cellulose - cellulase (present in bacteria, snails, arthropods) — in many vertebrate herbivores, microbiol communities of the gut (bacterial, fungi, yeasts & protists) are important for the digestion of cellulose; specialized fermentation chambers of non-acidic environment required — foregut fermenters (ruminants: cows, sheep); midgut fermenters (herbivorous fishes); hindgut fermenters (in cecum and/or colon: rabbits, horses, elephants) — products of cellulose are often short-chain fatty acids (volatile fatty acid), CO2 and methane gas — short-chain fatty acids are usually easily absorbed since they are both water and fat soluble — chitin - chitinase (present in frogs and other insect eating animals) Example of a foregut fermenter Examples of hindgut fermenters Other roles of gut microflora in addition to helping in digestion? — Metabolites and secretion products of these microflora have been shown to regulate the immune system of the host leading to decreased inflammatory and hypersensitivity responses. — Lowering of cancer rate, infection rate, blood pressure has also been proposed. — Concept of food containing probiotics (e.g., beneficial bacteria) and prebiotics (e.g., nutrients for enhancing the growth of beneficial bacteria) Quick Review of Enzymatic Digestion – Lipid 1 — triglycerides with a glycerol backbone and three fatty acid side-chains or a phosphosugar plus two fatty acid side- chains Quick Review of Enzymatic Digestion – Lipid 2 — digestion of lipid usually occurs in the intestine — small lipid droplets required for digestion - emulsifier needed (e.g., bile salts) — small lipid droplets hydrolyzed by lipases (secreted by pancreas in vertebrates) into glycerol and fatty acid components — chylomicrons (small lipid droplets coated in proteins) formed in epithelial cells of intestine — chylomicrons are carried via the lymphatic system to the venous blood and further processed in the liver From Eckert Quick Review of Enzymatic Digestion – Lipid 3 — once they enter the cell, glycerol and fatty acids can be processed through the Kreb’s cycle (TCA cycle - tricarboxylic acid cycle) and beta-oxidation pathways — in addition to NADH and FADH2, beta-oxidation yields AcetylCoA which also enters the Kreb’s cycle — Note: bile is alkaline so this terminates acidic gastric digestion; also carries water-insoluble wastes filtered from the blood in liver (e.g., steroids, cholesterol, hemoglobin, lipid soluble drugs) Quick Review of Enzymatic Digestion – Protein 1 — proteases or peptidases - endopeptidases and exopeptidases, endopeptidases usually act first — endopeptidase - break bonds in the “middle” of peptides (e.g., pepsin in stomach secretion, trypsin and chemotrypsin in pancreatic secretion) — pepsin requires acidic environment; trypsin and chemotrypsin require a slightly alkaline environment — exopeptidases - cleaves off terminal amino acids (amino- and carboxy-peptidases) - produced by pancreas — short peptide fragments result from gastric and pancreatic digestion — other exopeptidases (tripeptidases and dipeptidases) finishes off the digestion of the small peptide fragments in the intestine — amino acids and some dipeptides are absorbed by the gut epithelium via carrier-mediated transports (e.g., amino acid-Na+ co-transport) From: “Principles of Animal Physiology” by Moyes and Schulte, 2nd edition Quick Review of Enzymatic Digestion – Protein 2 Proline Alanine Glutamine Cysteine Histidine Glycine Arginine Serine Isoleucine Threonine Glutamate Methionine Valine KG Pyruvate α Citrate Succinyl CoA AcCoA Oxaloacetate Fumerate AcetoacetylCoA Phenylalanine Phenylalanine Asparagine Tyrosine Tyrosine Aspartate Leucine Lysine Tryptophan Quick Review of Enzymatic Digestion – others — nucleases, nucleotidases and nucleosidases act on nucleic acids and their residues — esterases act on esters (C-O-C; compounds formed from an alcohol and an acid) — although these processes do not yield products that lead to direct energy production, these products are essential building blocks for other complex molecules in the body Prevention of self-digestion of gut epithelium — thick layer of mucus secreted (sugar-based) — many proteases are secreted as inactive precursor molecules - proenzymes or zymogens — secretion of proenzymes also ensure that co-ordinated digestion is possible as they can be activated as needed, but only under correct conditions — pepsinogen (inactive proenzyme) can be cleaved by acid to pepsin (active enzyme); pepsin can also do this — under alkaline conditions, enterokinase released from the intestine cleaves off the 6 amino acids at the N-terminal of trypsinogen to produce trypsin; trypsin can also do this — trypsin also converts chymotrypsinogen to chymotrypsin Neural and Endocrine Control of Digestive Secretion General: — in vertebrates, control of digestive enzymes secretion is by both neural and endocrine means — neural - quick reflex responses — endocrine - more long-term control — many of these hormones are produced by endocrine cells dispersed throughout the epithelial lining of the gut (a diffused or dispersed endocrine system) — gastrointestinal hormones — also called the enterochromaffin-like cells system (entero- = gut; chromaffin - a cell-type stainable with silver salts) — many of these peptide hormones are also found in neurons in the CNS and in the peripheral nervous system (gut-brain peptides) Digestion in the oral cavity — chewing mechanically breaks down food and mixes food with saliva — amylase present in saliva (slightly alkaline) — amylase action starts carbohydrate digestion —
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