Lesson 1 Fundamentals of Nutrition

1. Lesson 1Fundamentals of Nutrition Mimi Giri, MD, Ph.D Department of Endocrinology, University Hospital of Ghent Ghent, Belgium

2. CarbohydrateNutrition and Metabolism • Introduction & Sources of carbohydrate in the diet • Structures • General functions of carbohydrate & Essentiality • Glucose from dietary carbohydrate: • digestion, absorption, transport into cells • Glucose metabolism: glucose disposal & synthesis: • Glucose disposal: Glycolysis, TCA cycle, FFA synthesis, NEAA synthesis; Glycogen synthesis • Glucose synthesis: purpose, glycogen breakdown and gluconeogenesis

3. Introduction Humans: ~ 50% of calories ingested as CHO (10 - 85%) 160 g starch, 120 g sucrose, 30 g lactose, 5 g glucose, 5 g fructose, trace maltose

4. Introduction Sources of carbohydrate: sucrose: “sugar” lactose: milk maltose: beer fructose: fruit, corn-syrup “processed foods” starch (amylose & amylopectin): wheat, rice, corn, barley, oats, legumes.... glycogen: muscle and liver

5. Introduction Glucose: ATP synthesis: all tissues RBC, tissues of eye, renal medulla, brain, intestines, white blood cells, skin: rely primarily on glucose as energy source in the fed state In the fed state, glucose is primarily obtained from dietary carbohydrate (CHO)

6. Structures Monosaccharides: Glucose, fructose, galactose Dissacharides: maltose: glucose + glucose lactose: glucose + galactose sucrose: glucose + fructose Polysaccharides: amylose: glucose + glucose +.... (linear) amylopectin: glucose + glucose +.... (branched) glycogen: glucose + glucose +...(very branched)

7. General functions of carbohydrates Energy: ATP synthesis (~ 4 kcal/g) NEAA synthesis: carbon skeleton Fat synthesis: via acetyl-CoA Glycogen synthesis TCA cycle intermediates Nucleotides: sugar portion Glycoproteins Glycolipids

8. protein polysaccharides lipids ADP + Pi ADP + Pi ADP + Pi ATP ATP ATP hexoses pentoses amino acids fatty acids urea cycle Overview of Metabolism ADP + Pi ADP + Pi ADP + Pi ATP ADP + Pi ATP ATP ATP pyruvate urea ADP + Pi acetyl-CoA O2 ATP electron transport chain oxidative phosphorylation e- citric acid cycle CO2 ATP

9. Fats Carbohydrates Proteins Fatty acids Simple Sugars Amino acids Overview of Catabolic Processes Stage 1 Stage 2 Stage 3 Glycolysis ATP Pyruvate Acetyl CoA Citric acid cycle Oxidative phosphorylation ATP

10. Use of Amino Acidsand Fatty Acids Fats and protein can also be used by the body as a source of energy. Not as easily used as carbohydrates. Liver glycogen glucose-6-P pyruvate Amino Acids or Fatty Acids

11. Essentiality of carbohydrates metabolic need is for glucose: ~300 g/d in humans - glucose can be made from most AAs (not Leu) - glucose can be made from propionate (SCFA) - glucose can be made from glycerol - glucose cannot be made from fatty acids CHO not strictly essential in diet Relying solely on AAs etc. as precurser for glucose not prudent or practical (except for carnivores), so......

12. Glucose from dietary carbohydrate: DIGESTION, ABSORPTION & TRANSPORT into cells Mouth salivary amylase: - hydrolyzes  1-4 bonds in starch - release: psychic (cephalic) stimuli mechanical stimuli: food in mouth chemical stimuli: food on taste buds - little digestion Stomach: Negligible

13. Stage One • Hydrolysis of food into smaller sub-units. Handled by the digestive system.

14. Stage One • Salivary glands: • Secrete amylase. • - digests starch. • Stomach: • Secretes HCl. • - denatures protein and pepsin. • Pancreas: • Secretes proteolytic enzymes and lipases. • - degrades proteins and fats.

15. Stage One • Liver and gallbladder: • Deliver bile salts. • - emulsify fat globules - easier to digest. • Small intestine: • Further degradation. • Produces amino acids, hexose sugars, fatty acids and glycerol. • Moves materials into blood for transport to cells.

16. CHO: Digestion, Absorption & Transport brush border lumen Small Intestine

17. CHO Digestion: SMALL INTESTINE LUMEN CCK lumen pancreas enzymes digesta CCK = cholecystekinin

18. Carbohydrate digestion: SMALL INTESTINE LUMEN pancreas enzymes lumen enzymes - -amylase cuts 1-4 bond in starch:maltose, limit dex. efficient and fast acting enzyme lumen (duodenum)

19. Carbohydrate digestion: SMALL INTESTINE Brush border enzymes occur on brush border maltase: cuts maltose -limit dextrinase: cuts 1-6 bond lactase: cuts lactose sucrase: cuts sucrose result: monosaccharides glucose, galactose, fructose

20. Carbohydrate: ABSORPTION • SITE OF ABSORPTION • Jejunum & Ileum • GLUCOSE/GALACTOSE • Absorbed by active transport • - sugars move against concn gradient • - requires ATP • Facilitated diffusion of glucose • - glucose concentration must be lower in enterocyte

21. Carbohydrate: ABSORPTION • FRUCTOSE • Carrier mediated facilitated diffusion • - fructose conc must be lower in enterocyte • CARBOHYDRATE TRANSPORT • - enterocyte to portal vein to liver • GLUCOSE UPTAKE INTO CELLS • - carrier mediated diffusion • - stimulated by insulin (muscle, liver, adipocyte)

22. Carbohydrate metabolism: • FRUCTOSE • liver: • fructose F-6-P DHAP glycolytic • pathway • GALACTOSE • liver: • galactose gal-1-P G-1-P G-6-P • glucose

23. Glucose metabolism: • glucose disposal & synthesis • SIGNIFICANCE • - Control blood glucose concentrations • in starvation, exercise, stress, refeeding... • 4 - 6 mmol/L (humans): 10 mM after meal • high blood sugar: damage lens, kidney etc. • complications of diabetes • low blood glucose: brain damage & death • - Control rate of glucose utilization in tissues

24. Control rate of glucose utilization in tissues • e.g. How does liver assess how much glucose is being used by muscle or brain? • e.g. When a high CHO meal eaten, rate of glucose absorption is high; to maintain normal blood glucose levels, the rate of glucose use in other tissues such as muscle must increase • Control & integration of glucose metabolism (disposal & synthesis) among tissues is required Liver plays a major role!!

25. Diet Liver as Glucostat Gut Amino Acids Glycerol Liver Lactic Acid Fat Muscle Blood Glucose 4.5-5.5 mmol/L Glands & other tissues Brain Kidney Urine BG >10mmol/L

26. Hunger Glucose absorption from gut Hepatic glycogenolysis Adrenaline Glucagon Gluconeogenesis in liver Insulin antagonist Growth Hormone Cortisol Insulin destroying enzymes Satiety Glucose diffusion in ECF Muscular exercise Insulin  Glucose oxidation  Glycogen deposition  Lipogenesis  Gluconeogenesis { glucosuria – in diabetes} Factors affecting glucose concentration Tend to raise Tend to lower

27. Fate of glucose glycogen synthesis ATP synthesis GLUCOSE NEAA synthesis FFA synthesis

28. Fate of glucose: • glycolysis, TCA cycle & FFA synthesis glucose ATP synthesis ATP pyruvate lactate FFA synthesis acetyl-CoA TCA cycle lots!! ATP

29. Fate of glucose: glycolysis & TCA cycle • purpose & tissues anaerobic glycolysis - RBCs, WBCs - kidney medulla - enterocytes - lens, cornea - skin - (skeletal muscle) glucose ATP pyruvate lactate FFA acetyl-CoA TCA cycle - make ATP (2 ATP/glucose) - maintain blood glucose

30. Fate of glucose: glycolysis & TCA cycle • purpose & tissues glucose aerobic glycolysis - brain - liver - skeletal muscle - kidney cortex - etc. ATP pyruvate acetyl-CoA - make ATP (32 ATP/glucose) - maintain blood glucose TCA cycle ATP

31. Fate of glucose: glycolysis & TCA cycle • stimulation and inhibition glucose stimulation - high glucose - low ATP - insulin inhibition - high ATP - FFAs ATP pyruvate lactate FFA acetyl-CoA TCA cycle ATP

32. Fate of glucose: FFA synthesis • tissues, stimulation • (generally only occurs if excess calories eaten) glucose mainly: liver adipocytes stimulation - high glucose - high ATP * - insulin pyruvate diet FFA acetyl-CoA TCA cycleTG ATP

33. Fate of glucose: NEAA synthesis • tissues, stimulation glucose mainly: liver muscles stimulation - high glucose - high ATP * - insulin pyruvate diet NEAA acetyl-CoA TCA cycleProteins ATP

34. Fate of glucose glycogen synthesis ATP synthesis glycolysis TCA cycle GLUCOSE NEAA synthesis FFA synthesis

35. Fate of glucose: glycogen synthesis • Liver & Muscle • glucose glycogen glycogen glycogen glucose gluc glucose glucose skeletal muscle Liver SI

36. Fate of glucose: glycogen synthesis • Liver & Muscle • glucose glycogen • stimulation: high glucose (liver) • insulin • low glycogen (muscle) glycogen glycogen glucose + ins gluc + ins glucose glucose skeletal muscle Liver insulin (ins) SI pancreas

37. Fate of glucose glycogen synthesis ATP synthesis GLUCOSE NEAA synthesis FFA synthesis glucose utilization result: decrease blood glucose level regulate tissue glucose use

38. Glucose synthesis: glycogen breakdown gluconeogenesis GLUCOSE glucose synthesis purpose: - maintain blood glucose level: fasting, sustained exercise, stress, hypoglycaemia - regulation of tissue glucose use tissues: liver, muscle, kidney

39. Glucose synthesis: glycogen breakdown (LIVER) • glycogen glucose immediate glucose source • stimulation: low blood glucose • adrenalin/glucagon • inhibition: insulin glycogen CO2 + glucagon glucose glucose glucose tissues glucagon SI Liver pancreas

40. Glucose synthesis: glycogen breakdown (muscle) • glycogen G-6-P (muscle) local use only • stimulation: adrenalin (exercise/stress) note: glycogen glycogen + adr G-6-P G-6-P CO2 lactate glucose skeletal muscle

41. Glucose metabolism: disposal & synthesis • Liver: major role in regulation of blood glucose • high blood glucose: glucose uptake glycogen CO2 FFA + i + i + i glucose glucose glucose + i SI + i = stimulated by insulin Liver

42. Glucose metabolism: disposal & synthesis • Liver: major role in regulation of blood glucose • low blood glucose: glucose release alanine lactate glycogen ala lactate +g glucose glucose SI Liver + g = stimulated by glucagon

43. Physiological importance of gluconeogenesis • low CHO diet, early starvation (no CHO intake), • infection & trauma (high glucose need) gluconeo- genesis glycogen glucose glucose brain & anaerobic tissues SI Liver

44. Regulation of glucose use among tissues and role of fatty acids • e.g. fed state/high CHO diet • glucose uptake and use glycogen ATP + ins glucose + ins gluc glucose Liver insulin (ins) SI pancreas

45. Regulation of glucose use fed state/high CHO diet glucose uptake and use glyc ATP CO2/ATP +ins ? glucose +ins gluc gluc glucose skeletal muscle Liver insulin (ins) SI pancreas

46. Regulation of glucose use • fed state/high CHO diet • role of fatty acids adipocyte TG FFA - ins FFA glyc ATP CO2/ATP - glucose + ins gluc gluc glucose skeletal muscle Liver insulin (ins) SI pancreas

47. CHO metabolism:Vitamin & Mineral Co-factors glucose biotin (carboxylation) Thiamine: Vit B1 Riboflavin: Vit B2 (FAD) Niacin: Vit B3 (NAD) pantothenic acid (Acetly-CoA) biotin B3 B3 B3 pyruvate lactate B1,B2,B3,Mg2+ pantothenic acid acetyl-CoA TCA cycle B1, B3

48. Diabetes Mellitus: Metabolism out of control • Introduction • Symptoms and clinical features • Metabolic effects of insulin on CHO metabolism • Metabolic effects on protein & fat metabolism • Lack of insulin (diabetes mellitus) • - effect on glucose uptake, utilization & production • - effect glucose production • - effect on protein synthesis & protein breakdown • - effect on TG breakdown (fat cells) • - effect on ketone body synthesis (liver)

49. Introduction • Diabetes Mellitus • or Type 1 (previously juvenile onset) • or insulin-dependent diabetes mellitus (IDDM) • recognized as a disease for 2000 years • -cells of Islets of Langerhans (pancreas) damage: inadequate insulin production • Diabetes illustrates problems that arise when integration of metabolism is impaired: • carbohydrate, protein & lipid metabolism

50. Symptoms and clinical features • polyuria • polydipsia • polyphagia • weight loss • dehydration • glycosuria • ketosis/ketoacidosis • unconsciousness/coma