SZM2.6 ANIMAL PHYSIOLOGY Physiology of the digestive system Lecture 3 1

This week contents Digestion and absorption, recap Control of appetite Gastrointestinal motility 2

Digestion & absorption 3

Food Processing

Human Digestion System

Oral Cavity At sight or smell of food, salivary glands secrete saliva – lubricates lining of mouth – Antibacterial agents – Amylase to hydrolyze starch Into the esophagus

The stomach What prevents gastric juice from digesting away the stomach lining? – Pepsin, an enzyme which begins the chemical digestion of protein, is secreted in the inactive form pepsinogen Protects the gastric gland cells – Mucus helps protect the stomach lining from both pepsin and acid – However, the stomach lining must be replaced about every 3 days

Small intestine Carbohydrate digestion start in duodenum and completed in rest of the small Protein digestion: Pancreas and duodenum secrete hydrolytic enzymes that break polymer into monomers (amino acids) Nucleic acid digestion: Pancreas and duodenum secrete hydrolytic enzymes which breakdown DNA & RNA polymers into nitrogenous bases, sugars, phosphates

Small intestine Nutrients are absorbed into the blood from the small intestine

Small intestine

Cont. Lipid digestion – Lipids reach stomach almost completely undigested, Why? – Fats are hydrophobic – Bile salts from gallbladder coat tiny fat droplets that keep them separated from each other, why is the separation of fats into small droplets beneficial for digestion? – More surface area is exposed, which allows the enzyme to breakdown the fats quickly

Large intestine Colon absorbs water Remains of undigested food become more solid as water is absorbed = Feces Consists mainly of plant fibers and prokaryotes

Summary of macromolecule digestion into subunits Disaccharides maltose sucrose lactose Monosaccharides gluose frucose galactose Polysaccharides starch (amylose) salivary amylase pancreatic amylase intestinal maltase sucrase lactase Proteins Peptides Amino Acids Endopeptidases: stomach pepsin pancreatic trypsin pancreatic chymotrypsin Exopeptidases: pancreatic intestinal Fats (triglycerides) Emulsified fats liver bile monoglycerides fatty acids glycerol direct absorption pancreatic lipase

Control appetite! 15

Hormonal Signals Regulate Feeding / Energy Expenditures CNS integrates sensory information with other information (smell, taste, psychological factors) to help regulate hunger and satiety, energy expenditures as well as growth and reproduction

Regulation of Hunger: Signals from Stomach and SI Involves polypeptide hormones secreted by the stomach and SI – Ghrelin stimulates hunger via effect in arcuate nucleus Secreted by stomach at high levels when stomach is empty and low levels when full – Cholecystokinin (CCK) from SI promotes satiety Levels rise during and immediately after a meal – Ghrelin and CCK regulate hunger on short-term, meal-to-meal basis Peptide YY (PYY) aka tyrosine secreted by SI in proportion to caloric content of food – Decreases hunger by signaling arcuate to decrease neuropeptide Y and stimulate MSH – Seems to serve intermediate level of control (injections reduce appetite for 12 hrs – inhibits gastric motility and increases water and electrolyte absorption in the colon.

Leptin Leptin is a hormone that is tied closely to regulating energy intake and expenditure, including appetite, metabolism and hunger. It influences the quantity of food consumed relative to the amount of energy expended If present in high levels= it signals to our brain that we’re full and can stop eating and that energy expenditure is to increase If low= we feel hungry. It stimulates receptors in the hypothalamus by binding to them and stimulating the release of appetite- suppressing chemicals. 18

Regulation of Hunger Leptin: – Secretion increases as stored fat increases – Signals body's level of adiposity – Stimulates arcuate to suppress Neuropeptide Y and agouti- related peptide and stimulate MSH Insulin may play role in satiety – Suppresses Neuropeptide Y Insulin stimulates adipose cells to secrete leptin – And is able to cross the BBB acts similar to leptin

The Action of Leptin Leptin crosses the BBB – To affect NTs released by neurons in the arcuate nucleus Influences other hypothalamic nuclei – Which in turn reduce appetite and increase metabolic rate

21 leptin (produced mostly by adipose tissue) LEVEL is high when you are full, low when you are hungry

CCK Causes the release of digestive enzymes and bile from the pancreas and gallbladder. It acts as a hunger suppressant. It plays a major role in inducing drug tolerance to opioids (e.g. morphine and heroin) Is partly implicated in experiences of pain hypersensitivity during opioid withdrawal. 22

Ghrelin Vs Leptin Ghrelin is a 28 AA hunger-stimulating hormone The ghrelin gene is made up of 4 exons and 3 introns (rats and humans). Precursors contain 117 amino acids (preproghrelin) released from the stomach and from neurons in the hypothalamic arcuate nucleus (ARC) (aggregation of neurons in the mediobasal hypothalamus) Its levels increase before meals and decrease after meals. Potently stimulates growth hormone release and food intake. 23

Ghrelin: the hormone that makes you feel hungry 24 Ghrelin expression in the rat stomach increases in an age dependent manner from neonate to adult and is unchanged by gonadal steroids

Structure of the human ghrelin gene and processing steps from the ghrelin gene to acyl ghrelin, des-acyl ghrelin or other ghrelin-associated peptides 25 Nishi et al. (2011) Peptides Volume 32, Issue 11 Pages 2175–2182Volume 32, Issue 11

Ghrelin Vs Leptin Leptin induces satiation when present at higher levels. Its action in the hypothalamus to regulate food intake and body weight is mediated by a neural circuitry comprising of orexigenic and anorectic signals. 26

Gastrointestinal motility 27 Hormonal control

Gastrin Polypeptide hormone with multiple forms Produced by G cell in the mucosal gland of gastric antrum and duodenum Can be found in fetal pancreatic islet, hypothalamus, medulla oblongata…etc Different forms, different activity, different tissues that are found G17 is the principal form of gastric acid secretion

Structure of gastrin

Action of gastrin Stimulation of gastric motility Stimulation of gastric acid and pepsin secretion Stimulate insulin secretion after protein meal Stimulation of mucosal growth in stomach and colon Release of histamine from ECL cell (the neuroendocrine cells found in the gastric glands of the gastric mucosa beneath the epithelium)

Regulation of gastrin secretion ↑ gastrin secretion Luminal: peptide, AA (phenylalanine, tryptophan), gastric distention Neural: vagal stimulation via gastrin-releasing peptide (GRP) Blood: Ca, epinephrine ↓ gastrin secretion Luminal: acid, somatostatin Blood: secretin, gastric inhibitory peptide (GIP), Vasoactive intestinal peptide (VIP), glucagon, calcitonin

Feedback inhibition of gastrin Acid in antrum inhibit gastrin secretion by 2 ways 1.Direct action on G cell 2.Stimulate release of somatostatin by D cell

Seminars to be presented on 16/11/2014 Topics: 1.Energy homeostasis (20 minutes) 2.Ghrelin sites of action (10 minutes) 3.Obesity and sleep (10 minutes) 4. Leptin, leptin resistance and its effects (10 minutes) 5.Hypothalamus… the ultimate controller (10 minutes) 34