AnSci 519

1. AnSci 519 Post-Absorptive CHO Metabolism Lance Baumgard

2. CHO digestion and absorption: monogastric vs ruminants

3. Post-Absorptive Terminology • Catabolism • Breaking down of a nutrient or tissue • Anabolic • Creating/synthesizing a tissue • Oxidation • Utilizing a nutrient to generate ATP, CO2 and H20 • Glycolysis • Breaking down of glucose…into pyruvate • Gluconeogenesis • Making of glucose…from non carbohydrate precursors • Glycogen • Storage form of glucose (Liver and muscle) • Glycogen synthesis (glycogenesis) • Glycogenolysis • TCA Cycle • Products of glycolysis enter TCA cycle and generate ATP

4. Primary Potential Fuel Sources • Volatile Fatty Acids (VFA) • Primarily in ruminants • Controversy on how much large intestine VFA in monogastrics contribute to energy • Non-Esterified Fatty Acids (NEFA): a.k.a Free Fatty acids • From adipose tissue break down • Amino Acids • Efficiency of capturing ATP from AA oxidation is very poor……large amount of heat released • Glucose • Absorbed from GIT • Released from liver (and kidney during starvation) • Gluconeogenesis and glycogen breakdown • Stored in muscle

6. Post-absorptive glucose metabolism • Options for absorbed glucose • 1) Oxidation: produces CO2 and H20 • 2) Glycolysis: • Production of pyruvate • TCA cycle (with O2) • Lactate (with no O2) • 3) Stored as glycogen • 4) Stored as fat • 5) Carbons utilized for amino acid synthesis Catabolic Anabolic

7. Types of Metabolic Pathways Catabolic Pathways: produce free energy compounds Anabolic Pathways:utilize these compounds

8. Overview of Dietary Catabolism

9. Glucose • The most important metabolic fuel in monogastrics are glucose and fatty acids. • The most important metabolic fuel in ruminants is acetate • In normal circumstances, glucose is the only fuel the brain uses • Can use ketones during starvation • Adult human brain requires ~120 g glucose/day • Whole body only requires ~160 g/glucose/day • ~20 g of glucose in circulation • Liver glycogen stores about ~150-180 g of glucose • Muscle glycogen stores about ~300-350 g of glucose • Only the liver can secrete/release glucose • Muscle can not

10. Glucose • To ensure the continuous provision of glucose to the brain and other tissues, metabolic fuels are stored when food is plenty • To provide glucose over longer periods, the body transforms non-carbohydrate compounds into glucose through gluconeogenesis. • Amino acids, lactate and glycerol

11. Glucose Oxidation Glycolysis (10 successive reactions) 2 Pyruvate Cytosol Mitochondria 2 Acetyl CoA O2 TCA Cycle CO2 NADH ATP Electron Transport Chain

12. Glycogen • Glycogen synthesis • Occurs in the liver and muscle • The synthesis of a branched polysaccharide form glucose….resembles amylopectin • Liver stores are especially important as an emergency source of blood glucose • Glycogenolysis • Breakdown of glycogen into glucose • Liver secretes the glucose, muscle only oxidizes glycogen released glucose

13. Gluconeogenesis Propionate (gut) Amino Acids (gut, muscle) Glycerol (fat mobilization) Glucose Lactic Acid (Gut & Cori Cycle)

14. Gluconeogenesis • Glucose requirements • Central nervous system • 15 – 20% of glucose utilization • Pregnancy • For fetus • Lactation • Lactose synthesis • Lipid synthesis • NADPH for fatty acid synthesis • Glycerol

15. Precursors for gluconeogenesis % of Glucose from: PrecursorFedFasted Propionate 40 – 60 0 Amino acids 15 – 30 35 (Primarily Alanine, Glutamine, Glutamate) Lactate 15 40 Glycerol 5 25

16. Gluconeogenesis Glucose Pyruvate Lactate and Amino acids Acetyl CoA OAA Amino Acids TCA Cycle Propionate (from rumen fermentation)

17. Mechanism of gluconeogenesis • Controlling enzymes • Pyruvate carboxylase (Pyr > OAA) • NAD-malate dehydrogenase (Mal > OAA) • PEP carboxykinase (OAA > PEP) • Fructose-1,6- diphosphatase (Fru-1,6-P > Fru-6-P) • Glucose-6-phosphatase (Glu-6-P > Glu) • Hormones • Glucagon and Glucorticoids • Insulin From Van Soest, 1994

18. Hormonal Control of Glucose Homeostasis • Insulin • Synthesized by the pancreas • Stimulated by increased glucose concentrations • Causes glucose storage (glycogen and fat) • Shuts down gluconeogenesis • Shuts down glycogenolysis • Glucagon • Synthesized by the pancreas • Stimulated by a reduction in glucose concentrations • Stimulates glycogenolysis AND gluconeogenesis • Epinephrine • Synthesized by the adrenal gland • Causes immediate glycogenolysis • Increase glucose during “flight or fight”

19. Glucose Coordinators Glucagon Epinephrine Cortisol Insulin Lipogenesis/Lipolysis Gluconeogenesis/Glycolysis Glycogenolysis/Glycogen Synthesis Anabolic Catabolic

21. Insulin Release Insulin secretion in beta cells is triggered by rising blood glucose levels. Starting with the uptake of glucose by the GLUT2 transporter, the glycolytic phosphorylation of glucose causes a rise in the ATP:ADP ratio. This rise inactivates the potassium channel that depolarizes the membrane, causing the calcium channel to open up allowing calcium ions to flow inward. The ensuing rise in levels of calcium leads to the exocytotic release of insulin from their storage granule.

22. Insulin Action Insulin binding to the insulin receptor induces a signal transduction cascade which allows the glucose transporter (GLUT4) to transport glucose into the cell.

24. Insulin vs. Glucagon

25. pancreatic islet b cells glucose insulin glucose glucose glucose fat cells GI tract

26. fat muscle pancreas Insulin Amino acids Glucagon liver Nutrient Director Glucose Circulating Nutrients Fatty acids Amino acids Glucose Fatty acids WELL FED ANIMAL High insulin levels Low glucagon and epinephrine GIT

27. fat muscle pancreas Amino acids Glucagon Insulin liver Nutrient Director Glucose gluconeogenesis & glycogenolysis Circulating Nutrients Fatty acids Amino acids Glucose Fatty acids HUNGRY ANIMAL Low insulin levels High glucagon and epinephrine GIT

28. History of Insulin • 1869 Paul Langerhans (German) was studying the structure of the pancreas when he noticed exocrine tissue. The function of the "little heaps of cells", later known as the Islets of Langerhans • 1889 German physician Oscar Minkowski removed the pancreas from a healthy dog to demonstrate the pancreas’s assumed role in digestion. • Several days after the dog's pancreas was removed, he noticed a swarm of flies feeding on the dog's urine • 1921: first patient injected with canine insulin • 1922: Eli Lilly purchases the patent for making insulin from the University of Toronto for $1 • 1980: Eli Lilly marketed the first synthetic insulin, Humulin (genetic engineered)

29. Type I Diabetic FemalePre and Post insulin treatment

30. Epinephrine produced by adrenal glands

32. meal 100 Blood glucose, mg/dl 90 80 absorption gluconeogenesis Reciprocity in patterns glycogenolysis Time after feeding (h)…

33. temporal pattern relative to CHO meal Glucagon Glucose Insulin Meal

34. Boo! Glucose Epinephrine

35. Post absorptive CHO metabolism: ruminants vs. monogastrics • Monogastrics: • Oxidize glucose for energy and energy storage • Blood glucose averages 80-100 mg/dl • Gluconeogenesis occurs many hours after a meal • Much of circulating glucose is diet derived • Ruminants: • Oxidizes acetate for energy and energy storage • Gluconeogenesis immediately after meal • ~100% of circulating glucose is derived from gluconeogenesis • Blood glucose averages 40-60 mg/dl • Circulating glucose is NOT derived from diet