Week 1 - Metabolic Physiology.pdf

WEEK 1: METABOLIC PHYSIOLOGY EHR522: EXERCISE FOR METABOLIC AND MENTAL HEALTH CONDITIONS Subject Coordinator: Tim Miller [email protected] 02 6338 4442 ORGANISATION OF THE GASTROINTESTINAL SYSTEM  Gastrointestinal Tract  A tube that is spec...

WEEK 1: METABOLIC PHYSIOLOGY EHR522: EXERCISE FOR METABOLIC AND MENTAL HEALTH CONDITIONS Subject Coordinator: Tim Miller [email protected] 02 6338 4442 ORGANISATION OF THE GASTROINTESTINAL SYSTEM  Gastrointestinal Tract  A tube that is specialised along its length for sequential processing of food  A series of hollow organs (mouth to anus) and accessory glands and organs that add secretions to the hollow organs  Each hollow organ serves a specialised function. They are separated at key locations by sphincters ORGANISATION OF THE GASTROINTESTINAL SYSTEM  Mouth and Oropharynx  Mechanical breakdown and lubrication of food  Propels food into the oesophagus  Initiates fat and carbohydrate metabolism  Oesophagus  Conduit to the stomach  Stomach  Temporary food storage  Churns and secretes proteases and acid that facilitate digestion ORGANISATION OF THE GASTROINTESTINAL SYSTEM  Small intestine  Continues digestion  Primary site for nutrient absorption  Large intestine  Reabsorbs fluids and electrolytes (but no nutrient absorption)  Storage of faecal matter before expulsion  Accessory glands include  Salivary glands  Pancreas  Liver ORGANISATION OF THE GASTROINTESTINAL SYSTEM  Pancreas  Digestive enzymes secretion  Secretion of bicarbonate to neutralise gastric acid  Secretion into the duodenum via the major and minor duodenal papilla ORGANISATION OF THE GASTROINTESTINAL SYSTEM  Liver  Bile secretion (stored in the gallbladder between meals)  Bile acids within bile, secreted at meal times, play a key role in fat digestion NUTRIENT DIGESTION AND ABSORPTION  Digestion – The enzymatic conversion of complex dietary substances to a form that can be absorbed  Most, but not all, digestive processes occur in the small intestine  Absorption – The process of up taking nutrients into cells or across tissues and organs through diffusion or osmosis CARBOHYDRATE DIGESTION  Carbohydrates are classified into three major groups  Monosaccharides (monomers)  Disaccharides (short polymers)  Polysaccharides (long polymers)  The small intestine can directly absorb monomers, but not polymers. In other words, carbohydrates require hydrolysis to monosaccharides before absorption  Some polymers are digestible, others are not  Non-digestible polymers = fibre CARBOHYDRATE DIGESTION  Dietary fibre – non-digestible polymers found in fruits, vegetables and cereals. Can be either soluble or non- soluble  Glycogen – the storage form of carbohydrate in animals. It is the starch equivalent for plants CARBOHYDRATE DIGESTION  Digestion of carbohydrates involves two steps  1) Intraluminal Hydrolysis – Starch to oligosaccharides by salivary and pancreatic enzymes  2) Membrane Digestion – Oligosaccharides to monosaccharides by brush border disaccharidases INTRALUMINAL HYDROLYSIS  Both salivary and pancreatic acinar cells synthesise and secrete alpha-amylases  Salivary amylase in the mouth initiates starch digestion. It is inactivated by gastric acid  Pancreatic alpha-amylase completes starch digestion in the lumen of the small intestine  The products of starch hydrolysis are disaccharides, which cannot be absorbed by the small intestine – further digestion is required to produce absorbable monosaccharides MEMBRANE DIGESTION  Membrane digestion involves hydrolysis of oligosaccharides to monosaccharides by brush border disaccharidases  The small intestine has three brush border oligosaccharidases, each with a different hydrolytic function  Lactase  Maltase  Sucrase - isomaltase CARBOHYDRATE ABSORPTION  The three monosaccharide products of carbohydrate digestion (glucose, galactose and fructose) are absorbed by the small intestine in a two-step process  1) Uptake across the apical membrane into the epithelial cell  2) Coordinated exit across the basolateral membrane CARBOHYDRATE ABSORPTION  The sodium/glucose transporter 1 (SGLT1) is the membrane protein responsible for glucose and galactose uptake at the apical membrane. This is an active transport process, with glucose moving against its concentration gradient  SGLT1 cannot carry fructose, so the apical step of fructose absorption occurs by the facilitated diffusion of fructose through GLUT5  The exit of all three monosaccharides across the basolateral membrane uses the facilitated sugar transporter, GLUT2 PROTEIN DIGESTION  Proteins must first be digested into their constituent oligopeptides and amino acids before being taken up by the enterocytes  Digestion-absorption of proteins occurs through four major pathways  1) Several luminal enzymes (proteases) from the stomach and pancreas may hydrolyse proteins to peptides and then to amino acids, which are then absorbed  2) Luminal enzymes may digest proteins to peptides, but enzymes present at the brush border digest the peptides to amino acids, which are then absorbed PROTEIN DIGESTION  3) Luminal enzymes may digest proteins to peptides, which are themselves taken up as oligopeptides by the enterocytes. Further digestion of the oligopeptides by cytosolic enzymes yields intracellular amino acids, which are moved by transporters across the basolateral membrane into the blood  4) Luminal enzymes digest dietary proteins to oligopeptides, which are taken up by enterocytes and moved directly into the blood  Brush border peptidases fully digest some oligopeptides to amino acids, whereas cytosolic peptidases digest oligopeptides that directly enter the enterocyte PROTEIN DIGESTION  Both gastric and pancreatic proteases, unlike the digestive enzymes for carbohydrates and lipids, are secreted as proenzymes that require conversion to their active form for protein hydrolysis to occur  The protein that is digested and absorbed in the small intestine comes from both dietary and endogenous sources  Of the 20 amino acids, nine are essential. That is, they are not synthesised in adequate amounts by the body and thus must be derived from either animal or plant sources PROTEIN, PEPTIDE AND AMINO ACID ABSORPTION  In adults, proteins are almost exclusively digested to their constituent amino acids and dipeptides, tripeptides or tetrapeptides before absorption  In contrast, during the neonatal period, the absorption of whole protein by apical pinocytosis occurs. This largely ceases six months of age, however even adults absorb small amounts of intact proteins  In adults, uncertainty exists regarding the cellular route by which these substances are absorbed, as well as the relationship of the mechanism of protein uptake in adults to that in neonates. PROTEIN, PEPTIDE AND AMINO ACID ABSORPTION  Although whole protein uptake in adults may not have nutritional value, such uptake is clearly important in mucosal immunity and probably is involved in one or more disease processes PROTEIN, PEPTIDE AND AMINO ACID ABSORPTION  Virtually all absorbed protein products exit the villous epithelial cell and enter the blood as individual amino acids  Substantial amounts of protein are absorbed from the intestinal lumen, via a H+-driven cotransporter, as dipeptides, tripeptides or tetrapeptides and are then hydrolysed to amino acids by intracellular peptidases  Additionally, substantial portions of amino acids are released in the lumen of the small intestine by luminal proteases and brush border peptidases and move across the apical membrane of enterocytes through one or more group-specific apical membrane transporters PROTEIN, PEPTIDE AND AMINO ACID ABSORPTION  The absorption of amino acids across the small intestine requires sequential movement across both the apical and basolateral membranes of the villous epithelial cell  Although the amino acid transport systems have overlapping affinities for various amino acids, the general consensus is that at least seven distinct transport systems are present at the apical membrane PROTEIN, PEPTIDE AND AMINO ACID ABSORPTION  Amino acids appear in the cytosol of intestinal villous cells as the result of either their uptake across the apical membrane or of the hydrolysis of oligopeptides that had entered the apical membrane  Movement of amino acids across the basolateral membrane is bi-directional; the movement of any one amino acid can occur through one or more amino acid transporters PROTEIN, PEPTIDE AND AMINO ACID ABSORPTION  At least five amino acid transporters are present in the basolateral membrane  Three amino acid transport processes on the basolateral membrane mediate amino acid exit from the cell into the blood and thus complete the process of protein assimilation  Two other amino acid transporters mediate uptake from the blood for the purposes of cell nutrition  Amino acids exit enterocytes through Na+- independent transporters and enter through Na+- dependent transporters LIPID DIGESTION  Lipids are typified by their preferential solubility in organic solvents, compared with water  The biological fate of lipids depends critically on their chemical structure, as well as on their interactions with water and other lipids in aqueous body fluids (eg. intestinal contents and bile)  Lipids may be either  Non-polar and completely insoluble in water  Polar and amphiphilic. That is, having both polar (hydrophilic) and non-polar (hydrophobic) groups LIPID DIGESTION  Typical adult Western diets contain approximately 140g of fat (providing approximately 55% of the energy requirements)  This is more than the recommended intake of less than 30% of total dietary calories (