Nutrients & Nutrient Sensing Systems Lecture Notes PDF

5/12/2024 NUTRIENTS & NUTRIENT SENSING SYSTEM PROFESSOR DR. FUNG SHIN YEE DEPARTMENT OF MOLECULAR MEDICINE FACULTY OF MEDICINE UNIVERSITY OF MALAYA...

5/12/2024 NUTRIENTS & NUTRIENT SENSING SYSTEM PROFESSOR DR. FUNG SHIN YEE DEPARTMENT OF MOLECULAR MEDICINE FACULTY OF MEDICINE UNIVERSITY OF MALAYA 1 [email protected] 1 LEARNING OBJECTIVES Basic characteristics of major nutrients – structures, functions, significance How the body senses nutrients & significance of this process : involvement of receptors (ie. G- protein coupled receptors (mechanism) Biochemical and pathological consequences of disordered Fate of carbohydrate, proteins, amino acid metabolism (ie. mechanism of glucose sensing lipids after ingestion Phenylketonuria) / carbohydrate absorption ie. Lactase deficiency) 2 2 1  5/12/2024 LECTURE CONTENT Introduction To Nutrition & Importance Of Macronutrients Major Nutrients: Carbohydrates –Simple And Complex Carbohydrates, Dietary Fibre Fats - Triacylglycerols, Phospholipids, Cholesterol Proteins And Amino Acids – Nitrogen Balance, Protein Quality Overview Of Digestion And Absorption Of Major Nutrients Nutrient-sensing Systems Transduction Mechanisms Involved In Nutrient Sensing Glucose Sensing In Pancreas Metabolic Effects Of Insulin 3 3 Introduction to nutrition DIET Energy sources Carbohydrates Fats Proteins (Alcohol) Roles of nutrients in humans: Energy Essential fatty acids Building materials Regulatory compounds Essential amino acids Vitamins 4 Minerals 4 2  5/12/2024 Contribution of macronutrients to energy (Alcohol) Protein = 4 kcal/g Fats = 9 kcal/g Carbohydrate = 4 kcal/g 5 (Alcohol = 7 kcal/g) 5 Components of energy expenditure types, intensity & times spent in different activities Diet-induced G aregulation importantor thermogenesis : and energy balance Energy required for BMR of adult male = 1800 kcal the digestion, absorption and BMR of adult female = 1300 kcal transport of nutrients. in response  Energy needed for vital functions (i.e Cold-induced -heat production maintaining electrolyte equilibrium -importantsureforcells thermogenesis to cold exposure , making tissue across cell membranes, cell & protein function properly involves brown adipose and muscle contraction turnover, respiratory & cardiovascular activation functions, etc) regulated by sympathetic 6 system.  Energy required in a resting individual, nervous free from physical and emotional activities 6 3  5/12/2024 DIETARY CARBOHYDRATE SIMPLE SUGARS COMPLEX SUGARS Monosaccharide Glucose Polysaccharide Fructose Glycogen, Starch (amylose, Disaccharide amylopectin) Sucrose Non-starch polysaccharide Lactose Fibre Maltose monosaccharide Glucoaes disaccharide 7 7 SIMPLE SUGARS MONOSACCHARIDES simple sugars cannot be broken down into smaller units DISACCHARIDES  2 monosaccharide units  linked by glycosidic bonds OLIGOSACCHARIDES: 3-9 monosaccharides often associated with proteins (glycoproteins) and lipids (glycolipids) 8 8 4  5/12/2024 POLYSACCHARIDES 9 9 POLYSACCHARIDES combination of many of the STARCH: & same monomers.  homopolysaccharides  mixture of 2 glucose polymers: amylose & amylopectin  amylose: amyose to  1→4 linkage  straight-chain polysaccharide  amylopectin:  α,1→4 and α,1→6 linkages  branched-chain polysaccharide (branch point every 30 residues) pee ↑ tin bran and =. & 10 10 5  5/12/2024 POLYSACCHARIDES gly Eugen GLYCOGEN:  branched polymer of glucose  more highly branched than amylopectin (branch point every 8-10 residues) 11  main carbohydrate reserve in the body 11 POLYSACCHARIDES o CELLULOSE unbranched polymers of glucose linked by β,1→4 glycosidic bonds plant cell wall and fibre non-digestible 12 12 6  5/12/2024 13 13 14 14 7  5/12/2024 15 15 16 16 8  5/12/2024 17 17 FATS 18 18 9  5/12/2024 FATS e TRIACYLGLYCEROL (TAG)  important energy source 19  95% of the fats in the diet 19 20 20 10  5/12/2024 O 21 21 ESSENTIAL FATTY ACIDS not produced by human body. > - blood clotting > - immune response > - blood flow. 22 22 11  5/12/2024 a eveggie on ment 3trad Deficiency symptoms: > flaky skin  Scaly dermatitis -  Hair loss  Delayed wound healing  Membrane damage (abnormalities of erythrocytes & mitochondria) 23 23 TYPES OF FATTY ACIDS 24 24 12  5/12/2024 OTHER DIETARY FATS without cholestend PHOSPHOLIPIDS CHOLESTEROL membrane will not be fluid structural components membrane component preentor before (membrane, bile) precursors of bile acids, steroid - > make hormonea , precursors of 2nd messenger hormones, vitamin D (phosphotidylinositol bisphosphate), prostaglandins lung surfactant (dipalmitoyllecithin) O HO O CH2 O C R1 R2 C O C H O CH2 O P O X - O 25 25 26 26 13  5/12/2024 A short video to end this hour…. 27 Vitaminr s e blockof the 27 ↑ building fatshelpabsorbNutrientarement a a ecelsstayhadd protein - > 16 % of human weight He O ↳ made of amino acids ↳ Canghorenal helps skin , eyes ↑ , minerals > - In re healing factor cares - > brain Good > - metabolism , , nervous ↳ immunity hormone > - Fe to 28 28 14  5/12/2024 NUTRIENTS & NUTRIENT SENSING SYSTEM PROFESSOR DR. FUNG SHIN YEE DEPARTMENT OF MOLECULAR MEDICINE FACULTY OF MEDICINE UNIVERSITY OF MALAYA 1 [email protected] 1 Proteins Proteins: Function: Polymers of amino acids Structural components of 20 different amino acids tissues (connective tissues, Determined by Cside chain ‘R’ hair, cytoskeleton) Organ building Growth & maintenance Enzymes, hormones, ion channels, oxygen transport Basic ‘machinery’ of all cells 2 2 1  5/12/2024 3 3 AMINO ACIDS WITH NONPOLAR SIDE CHAINS CHARACTERISTICS: in aqueous solutions: non-polar side chains cluster together in interior of protein 4 4 2  5/12/2024 Amino Acids With Polar Side Chains OH-bond) Characteristics: On-Ph.  OH group: participate in hydrogen bond formation, attachment site for structures ie. phosphate group  -SH: sulfhydryl group (component of active site of many enzymes, stabilize proteins) 5  NH2 group: attachment site for oligosaccharide chains in glycoproteins 5 Nb > - Oligosaccharides · Amino Acids With Acidic Side Chains Characteristics:  side chains can donate H+ Acidonate Amino acids with basic side chains Characteristics :  Side chains can accept H+ Basic ept 6 6 3  5/12/2024 Peptide bonds link amino acids 1 2 Peptide bonds: formed by linking the α–carboxyl group of one amino acid to the α– amino group of another amino acid. 7 Accompanied by loss of a water molecule. bond 7 L - carboxyl group - X-amino group : peptide Gilang air) Amino acids can't make them y body - get from food Essential amino acids: Cannot be synthesized by human Lack of enzymes in the biosynthetic pathway Must be supplied in the diet 8 8 4  5/12/2024 Phenylketonuria Phenylketonuria (PKU): disorder of amino acid metabolism (hereditary ↳ disease that occurs 1 in 10,000) - deficiency of Phe hydroxylase premolketonuria doxylase Karang. Phe Hydroxylase alam break down * phenylalanine. Treatment: diet low in phenylalanine (avoid sweetener: aspartame) adequate tyrosine in diet 9 9 Phenylketonuria CONSEQUENCES OF PKU: Impaired downstream metabolism Phenylalanine Phenylketones Impaired synthesis of tyrosine, dopamine and catecholamine neurotransmitters  Elevated serum phenylalanine (normal 50- 80 µM; PKU: up to 2 mM) Tyrosine Catecholamines Generation of phenylketones (phenylalanine, phenylpyruvate,  phenyllactate & phenylacetate)  Melanin Mental retardation: demyelination, impaired protein synthesis in brain Fumarate & Acetoacetate Tissue proteins 10 10 5  5/12/2024 Carbohydrate Digestion amylate > - orgo Sacramble disaccharide salivary & pancreatic amylase: breakdown starch to oligosaccharides and disaccharides disaccharidases & debranching enzymes: breakdown oligosaccharides & disaccharides to monosaccharides monosaccharides are absorbed undigested carbohydrates: metabolised by bacterial enzymes (large intestine) to short chain fatty acids, lactate, hydrogen gas, methane, CO2 11 Biochemistry: Lippincott’s Illustrated Reviews 11 Carbohydrate Digestion: Lactose Intolerance lactase deficiency (ie. associated with gastroenteritis in infants) Lactase: membrane bound enzyme in brush border of small intestine biochemical problem: unable to breakdown lactose to galactose and glucose clinical features: diarrhea, weight loss, inadequate nutrition treatment: reduce intake of dairy products 12 http://www.wiley.com/college/boyer/0470003790/cutting Biochemistry: Lippincott’s Illustrated Reviews _edge/lactose_intolerance/lactose_intolerance.htm 12 6  5/12/2024 Lipid Digestion digestion begins in stomach by acid-stable lipase (very limited) main site for lipid digestion: small intestine pancreatic juice: lipase = lipid lipase: hydrolyses tag to free fatty acids & monoacylglycerol bile salts emulsify tag for action of lipase esterase: hydrolyses cholesterol esters phospholipase: hydrolyses phospholipids esterase ester phospholipase = phospholipids· 13 Biochemistry: Lippincott’s Illustrated Reviews 13 Protein Digestion proteolytic enzymes produced by stomach, pancreas, small intestine stomach: proteins hydrolysed to peptides and some amino acids small intestine: pancreatic enzymes hydrolyse peptides to oligopeptides and amino acids enzymes on luminal surface of epithelial cells hydrolyse di- and oligo-peptides to free amino acids and di- and tri-peptides amino acids are absorbed in small intestine 14 Biochemistry: Lippincott’s Illustrated Reviews 14 7  5/12/2024 Clinical Correlation: Celiac Disease malabsorption due to immune-mediated damage to small intestine gut becomes flat due to gluten ingestion gluten: a protein found in wheat, barley, rye symptoms: diarrhoea, weight loss, anaemia 15 http://yourdoctorsorders.com/2011/09/gluten-a-short-course/ 15 16 16 8  5/12/2024 17 17 How Does The Body Detect/Sense Nutrients? sweet mono di TASTE:  Sweet (Mono And Disaccharides)  Umami (Amino Acid Glutamate) Nutritive /  Salt (Na+ Or K+) beneficial?  Bitter  Sour (Low pH)  Fatty Acids? harmful / toxic? STOMACH AND INTESTINE:  Peptides/Amino Acids; Monosaccharides (Glucose); Fatty Acids INTERNAL SENSING  CNS; endocrine glands; tissues 18 18 9  5/12/2024 ? ghrelin insulin ? cholecytokinin ? Nutrient Sensing IMPORTANCE  regulate food intake (control appetite & satiety)  ghrelin (produced by stomach): induces appetite  insulin (produced by pancreas): decreases appetite  food selection and anticipation of nutrient abundance  coordination of hormonal responses to food  coordination of digestion  cholecystokinin : stimulate protein/fat digestion  regulation of growth and/or nutrient storage *Mammalian target of rapamycin (mTOR) regulates cell proliferation, autophagy, and apoptosis by participating in multiple signaling pathways in the body. Studies have shown that the mTOR signaling pathway is also associated with cancer, arthritis, insulin resistance, osteoporosis, and other diseases. (Nrf2) is an essential transcription factor that regulates an array of detoxifying and antioxidant defense gene expression in the liver 19 19 S Bitter , Sweet umami , ↓ bind G PeMR ↓ IP, ↑ , Ca2tq inositol triphosphate ↓ Transient receptor open channel t. Depolarized 20 20 10  5/12/2024 Transduction Mechanism In Taste Cells Detected By G Protein-coupled Receptors (GPCR) GPCR has 7 transmembrane domains consist of T1R AND T2R families T2R umami taste: detected by T1R1 + T1R3 Second sweet taste: detected by T1R2 + T1R3 messenger G Prot bitter taste: detected by T2R 71R1 + T1R3 G proteins: membrane proteins, contain α,β,γ subunits T1R2 + T113 Neurotransmission  Transduction mechanism:  Binding of ligand to receptor  Activation of G-protein  Stimulation of 2nd messenger 21  Release of neurotransmitter 21 Transduction Mechanisms In Taste Cells bila gate Na "buak, auto Ca2+ bubal. pun + Kena block dengan #T , so Ca2 + je bulak. sour taste: detected by direct interactions with ion channels (h+ ions) salty taste: 22 detected directly by their passage through ion channels on surface of cells in the tongue (i.e amiloride-sensitive sodium channel (ENaC) 22 11  5/12/2024 23 23 24 24 12  5/12/2024 Biological Effects Of Taste Receptor Activation T1Rs : sweet and umami T2Rs : bitter PYY: pancreatic peptide YY GLP-1: glucagon-like peptide 1 Enrique Rozengurt Am J Physiol Gastrointest Liver Physiol 2006;291:G171-G177 GIP: gastric inhibitory polypeptide CCK: cholecystokinin 25 gene Glucose Sensing In Pancreas ① Fatty acid GPR- 40 g ② could glucose is primary stimulus of insulin maintanam secretion Glucose-stimulated insulin release ⑧ blood glucose level rises & glucose uptake eveinein. ⑤ open glucose metabolism generation of ATP closure of K+ channel: membrane exocytosis. potential change Ca2+ influx insulin secretion blood glucose level falls 26 http://www.nature.com/nm/journal/v13/n3/full/nm0307-241.html 26 13  5/12/2024 Metabolic Effects Of Insulin CARBOHYDRATE METABOLISM: E promotes glucose storage increased glucose metabolism in liver & muscle increased glycogen synthesis in liver & muscle increased glucose uptake in muscle & adipose (GLUT-4) LIPID METABOLISM: Triglyceride - promotes conversion of glucose to TAG in liver reduced hydrolysis of TAG in adipose PROTEIN METABOLISM: stimulates entry of amino acids into cells for protein synthesis 27 27 28 28 14  5/12/2024 What Have We Learnt ? Three Major Nutrient Groups: Carbohydrate, Fats, Protein (Important Mainly As Energy Sources) Proteins: Polymers Of Amino Acids Carbohydrates: Polymers, Oligomers Or Monomers Of Simple Sugars Dietary Fat: Mainly Triglyceride (Glycerol Esters Of “Fatty Acids”) Small Intestine: Primary Site Of Nutrient Digestion And Absorption Nutrient Sensing Mechanisms: Appetite, Food Selection, Satiety, Coordinate Hormonal & Digestive Responses, Control Growth & Nutrient Storage 29 29 30 30 15  5/12/2024 31 31 32 32 16