Lecture 6: Diabetes, sugar, and ATP

1. If you could peer into the crystal ball and see how you were going to die, would you do anything different?

2. Objectives Understand how sugar metabolism works Understand how to make ATP Understand where sugar comes from Understand how sugar metabolism affects you Key Terms metabolism, gradient, equilibrium, phosphorylation, ATP, ADP electron transport, glycolysis, insulin, glycogen, glucagon NEXT WEEK: Cell Division and Cancer Lecture 6: Diabetes, sugar, and ATP

3. Leading Causes of Deaths • Heart Disease: 700,142 • Cancer: 553,768 • Stroke: 163,538 • Lung diseases: 123,013 • Accidents (unintentional injuries): 101,537 • Diabetes: 71,372 • Influenza/ Pneumonia: 62,034 • Alzheimer's disease: 53,852 • Kidney Disease: 39,480 • Septicemia (infection): 32,238 (Most current data available are for U.S. in 2001) www.cdc.gov/nchs/fastats/lcod.htm

4. I don’t have to worry about that stuff till I get old! All races, both sexes, 20–24 years • Accidents (unintentional injuries) • Assault (homicide) • Intentional self-harm (suicide) • Cancer • Heart disease • Genetic abnormalities • Human immunodeficiency virus (HIV) • Stroke • Influenza and pneumonia • Diabetes Relative to the national population of 20-24’s, are MSU students less likely to die from the top 3? It’s difficult for one to prevent bad luck, or being a victim?

5. Two Types of Diabetes Type 1 • Juvenile diabetes • Autoimmune disease • Beta cells in pancreas are killed by defense responses • Treated with insulin injections Type 2 • Adults affected • Insulin sensing system impaired. • Beta cells stop making insulin. • Pancreas burns out • Treated with diet, drugs

6. Diabetes Mellitis • Cells in muscles, liver and fat don’t use insulin properly • Disease in which excess glucose accumulates in blood, then urine • Signs and Symptoms • Excessive urination • Constant thirst and or hunger • Fatigue • Weight loss • Blurred vision • Sores that don’t heal

7. Risk Factors • Age • Overweight • Inactive (exercise > 3x/week) • Family history: African, American Indian, Asian, Pacific Islander, Hispanic or Latino descent. • Siblings or parents have diabetes • Gestational diabetes • Blood pressure over 140/90 • HDL (good) cholesterol is low and triglicerides are high

8. Reducing Risks • Physical activity- 30 min 5 days/week • Diet Modification • Low fat- 25% of calories max • Low alcohol • Maintain Reasonable body mass • No crash diets • Modify dietary intake

9. What, me worry? • Myths: • When I leave MSU and get a job I will have as much or more free time than I do now. (I’ll still exercise as much as I do now. • I’m naturally healthy, I don’t have to worry. • I don’t have any risk factors so I’m immune!

10. Diabetes Prevention Program Program Risk Reduction • Healthy diet and exercise 58% • Healthy diet and exercise (old folks) 71% • Prevention drug 31% • Control group (no change) Participants were overweight, with high blood sugar (Pre-Diabetes, impaired tolerance)

11. Question #1 Energy for metabolic processes only comes from Sugar A. True B. False

12. Quick Anatomy Review IN MOUTH(ORAL CAVITY) PHARYNX ESOPHAGUS STOMACH LIVER GALLBLADDER SMALL INTESTINE PANCREAS LARGE INTESTINE (COLON) RECTUM OUT ANUS

13. INTESTINAL LUMEN Monosaccharides (simple sugars) carbohydrates proteins amino acids EPITHELIAL CELL INTERNAL ENVIRONMENT Absorption Mechanisms • Food is broken down to macro molecules • Macro molecules are disassembled by enzymes in the intestines • Actively transported across membrane: • Monosaccharides • Amino acids • Nutrients diffuse from gut cells into blood stream

14. bile salts + bile salts FAT GLOBULES MICELLES carbohydrates EMULSIFICATION DROPLETS proteins EPITHELIAL CELL CHYLOMICRONS INTERNAL ENVIRONMENT

15. Krispy Kreme Donuts (12) Control of Glucose Metabolism insulin Glucose is absorbed Glucose uptake Glucose to glycogen Glucose falls Cells use glucose Glucose rises Glycogen to glucose glucagon

16. Many cells, especially muscle cells, take up glucose and use it as an energy source or convert it to glycogen. INSULIN Beta cells of pancreas release insulin into blood. Liver converts glucose to glycogen, fats, proteins. Blood glucose levels decline to a set point; stimulus calling for insulin diminishes. Stimulus: Glucose is absorbed following a meal. Stimulus: Cells use or store glucose between meals. Blood glucose levels increase to a set point; stimulus calling for glucagon diminishes. Liver converts glycogen to glucose, stops synthesizing glycogen. Alpha cells of pancreas release glucagon into blood. GLUCAGON

17. IF YOU ARE LOSTCLOSE YOUR EYESTILL UNTIL AFTERTHE NEXT SLIDE

18. Insulin Glucose

19. Click to view animation. animation

20. Using GlucoseSkeletal Muscle Structure • A muscle is made up of muscle cells • A muscle fiber is a single muscle cell • Each fiber contains many myofibrils myofibril Don’t Write This Down

21. sarcomere sarcomere sarcomere sarcomere Z band Z band Z band Myofibril A myofibril is made up of thick and thin filaments arranged in sarcomeres Don’t Write This Down

22. Sarcomere A bundle of two types of microfilaments ThinFilaments ThickFilaments Don’t Write This Down

23. Muscle Microfilaments Thick filaments • Composed of myosin • Each myosin molecule has tail and a double head Thin filaments • Like two strands of pearls twisted together • Pearls are actin • Other proteins in grooves in filament Don’t Write This Down

24. Sliding-Filament Model Sarcomere shortens because the actin filaments are pulled inward, toward the sarcomere center Don’t Write This Down

25. Sliding-Filament Model • Myosin heads attach to actin filaments • Myosin heads tilt toward and pull on the actin. Key Concept: • Each head requires one ATP for each pull! • There a lot of myosinheads in a muscle • Muscle contraction requires enormous quantities of ATP!

26. Key Concept:Contraction Requires Energy • Muscle cells require huge amounts of ATP energy to power contraction • The cells have only a very small store of ATP • There are three pathways muscle cells use to get ATP

27. Question #2 Cells burn insulin to make ATP A. True B. False

28. ATP for Contraction ADP + Pi Pathway 1 DEPHOSPHORYLATION CREATINE PHOSPHATE Relaxation Contraction creatine Pathway 2 AEROBIC RESPIRATION Pathway 3 GLYCOLYSIS ALONE glucose from bloodstream and from glycogen breakdown in cells oxygen

29. What is ATP? ? DEPHOSPHORYLATION! RESPIRATION! GLYCOLYSIS! What’s ATP! AND How did we get here and where are we going

30. ATP Is Universal Energy Source • Photosynthesizers get energy from the sun • Animals get energy second- or third-hand from plants or other organisms • Regardless, the energy is converted to the chemical bond energy of ATP

31. Making ATP • Plants make ATP during photosynthesis • Cells of all organisms make ATP by breaking down carbohydrates, fats, and protein

32. Aerobic pathways SLOW Require oxygen Start with glycolysis in cytoplasm Completed in mitochondria (Note: special membrane and gradient) Anaerobic pathways FAST Don’t require oxygen Start with glycolysis in cytoplasm Completed in cytoplasm Two Main Pathways for making ATP

33. Overview of Aerobic Respiration CYTOPLASM glucose ATP GLYCOLYSIS energy input to start reactions (2 ATP net) e- + H+ 2 pyruvate 2 NADH MITOCHONDRION e- + H+ 2 CO2 2 NADH e- + H+ 4 CO2 8 NADH KREBS CYCLE e- + H+ 2 ATP 2 FADH2 e- ELECTRON TRANSPORT PHOSPHORYLATION 32 ATP H+ water e- +oxygen TYPICAL ENERGY YIELD: 36 ATP

34. Overview of Aerobic Respiration C6H1206 + 6O2 6CO2 + 6H20 glucose oxygen carbon water dioxide

35. Overview of Aerobic Respiration CYTOPLASM glucose ATP GLYCOLYSIS energy input to start reactions (2 ATP net) e- + H+ 2 pyruvate 2 NADH MITOCHONDRION e- + H+ 2 CO2 2 NADH e- + H+ 4 CO2 8 NADH KREBS CYCLE e- + H+ 2 ATP 2 FADH2 e- ELECTRON TRANSPORT PHOSPHORYLATION 32 ATP H+ water e- +oxygen TYPICAL ENERGY YIELD: 36 ATP

36. How it Works: Pull a hydrogen off a water (HOH to OH-) Pull the hydrogen (H+) across a membrane (electrochemical GRADIENT) Make the H+ do work on its way back to OH- Difficult to explain without using lots of really cool chemistry Key concept: If you pull water apart, it really wants to get back together again By giving the Oxygen atom in water an electron, it will give you a proton, which is actually a H+ Oxygen is the final electron acceptor? What’s the deal with Oxygen?(electron transport chain over simplified) http://www.sp.uconn.edu/~terry/images/anim/ETS.html

37. Question #3 More ATP is produced by the electron transport system than is produced by glycolysis A True B False

38. Coenzyme Production • Glycolysis 2 NADH • Preparatory reactions 2 NADH • Krebs cycle 2 FADH2 . 6 NADH • Total 2 FADH . 10 NADH • Key Concepts: Coenzyme production • Kreb’s cycle produces activated coenzymes • Coenzymes push electron transport

39. Making ATP: Chemiosmotic Model ATP INNER COMPARTMENT ADP+Pi

40. ATP Synthase in Action

41. Key Points In Summary • Glucose eventually gets broken down to carbon dioxide gas • Two ways to make ATP • Fast way - Anerobic • No oxygen required • Glucose isn’t converted to CO2 but lactic acid • Only net 2 ATPs/glucose • Slow way - Aerobic • Requires oxygen • Glucose converted to CO2 • Net 36 ATPs/glucose

42. Efficiency of Aerobic Respiration • 686 kcal of energy are released • 7.5 kcal are conserved in each ATP • When 36 ATP form, 270 kcal (36 X 7.5) are captured in ATP • Efficiency is 270 / 686 X 100 = 39 percent • Key Concept: Most energy is lost as heat

43. Anaerobic Pathways • Do not use oxygen • Produce less ATP than aerobic pathways • Two types • Fermentation pathways • The burn • The Buzz • Anaerobic electron transport

44. Fermentation Pathways • Begin with glycolysis • Do not break glucose down completely to carbon dioxide and water • Yield only the 2 ATP from glycolysis • Steps that follow glycolysis serve only to regenerate NAD+

45. Lactate Fermentation GLYCOLYSIS C6H12O6 ATP 2 energy input 2 NAD+ 2 ADP NADH 2 ATP 4 2 pyruvate energy output 2 ATP net LACTATE FORMATION electrons, hydrogen from NADH 2 lactate

46. Yeasts • Single-celled fungi • Carry out alcoholic fermentation • Saccharomyces cerevisiae • Baker’s yeast • Carbon dioxide makes bread dough rise • Saccharomyces ellipsoideus • Used to make beer and wine • MSU hard cider project: Sacchromyces banyan DV10

47. GLYCOLYSIS Alcoholic Fermentation C6H12O6 2 ATP 2 NAD+ energy input 2 ADP NADH 2 ATP 4 2 pyruvate energy output 2 ATP net ETHANOL FORMATION 2 H2O 2 CO2 2 acetaldehyde Animals Can’t do this! electrons, hydrogen from NADH 2 ethanol

48. Anaerobic Electron Transport • Carried out by certain bacteria • Electron transport system is in bacterial plasma membrane • Final electron acceptor is compound from environment (such as nitrate), NOT oxygen • Doesn’t require Oxygen • Can’t work with Oxygen • ATP yield is low • Lets bacteria live where other organisms can’t

49. Question #4 Is Insulin a: A. Carbohydrate B. Protein C. Lipid D. Organophosphate

50. Energy Reserves • Glycogen is about 1 % of the body’s energy reserve • Proteins is 21% of energy reserve • Fat makes up the bulk of reserves (78 %) • Note: In lecture 4 we discussed polysaccharides, proteins and lipids.