Carbohydrate Metabolism

1. Carbohydrate Metabolism

2. An Overview of Metabolism

3. Adenosine Tri-Phosphate (ATP) • Link between energy releasing and energy requiring mechanisms • “rechargeable battery” ADP + P + Energy ATP

4. Mechanisms of ATP Formation • Substrate-level phosphorylation • Substrate transfers a phosphate group directly • Requires enzymes Phosphocreatine + ADP Creatine + ATP • Oxidative phosphorylation • Method by which most ATP formed • Small carbon chains transfer hydrogens to transporter (NAD or FADH) which enters the electron transport chain

5. Metabolism • Metabolism is all the chemical reactions that occur in an organism • Cellular metabolism • Cells break down excess carbohydrates first, then lipids, finally amino acids if energy needs are not met by carbohydrates and fat • Nutrients not used for energy are used to build up structure, are stored, or they are excreted • 40% of the energy released in catabolism is captured in ATP, the rest is released as heat

6. Anabolism • Performance of structural maintenance and repairs • Support of growth • Production of secretions • Building of nutrient reserves

7. Catabolism • Breakdown of nutrients to provide energy (in the form of ATP) for body processes • Nutrients directly absorbed • Stored nutrients

8. Cells and Mitochondria • Cells provide small organic molecules to mitochondria • Mitochondria produce ATP used to perform cellular functions

9. Metabolism of Carbohydrates

10. Carbohydrate Metabolism • Primarily glucose • Fructose and galactose enter the pathways at various points • All cells can utilize glucose for energy production • Glucose uptake from blood to cells usually mediated by insulin and transporters • Liver is central site for carbohydrate metabolism • Glucose uptake independent of insulin • The only exporter of glucose

11. Blood Glucose Homeostasis • Several cell types prefer glucose as energy source (ex., CNS) • 80-100 mg/dl is normal range of blood glucose in non-ruminant animals • 45-65 mg/dl is normal range of blood glucose in ruminant animals • Uses of glucose: • Energy source for cells • Muscle glycogen • Fat synthesis if in excess of needs

12. Fates of Glucose • Fed state • Storage as glycogen • Liver • Skeletal muscle • Storage as lipids • Adipose tissue • Fasted state • Metabolized for energy • New glucose synthesized Synthesis and breakdown occur at all times regardless of state... The relative rates of synthesis and breakdown change

13. High Blood Glucose Pancreas Muscle Glycogen Insulin Glucose absorbed Glucose absorbed Adipose Cells Glucose absorbed immediately after eating a meal…

14. Glucose Metabolism • Four major metabolic pathways: • Energy status (ATP) of body regulates which pathway gets energy • Same in ruminants and non-ruminants • Immediate source of energy • Pentophosphate pathway • Glycogen synthesis in liver/muscle • Precursor for triacylglycerol synthesis

15. Fate of Absorbed Glucose • 1st Priority: glycogen storage • Stored in muscle and liver • 2nd Priority: provide energy • Oxidized to ATP • 3rd Priority: stored as fat • Only excess glucose • Stored as triglycerides in adipose

16. Glucose Utilization Adipose Energy Stores Glycogen Glucose Pentose Phosphate Pathway Glycolysis Ribose-5-phosphate Pyruvate

17. Glucose Utilization Adipose Energy Stores Glycogen Glucose Pentose Phosphate Pathway Glycolysis Ribose-5-phosphate Pyruvate

18. Glycolysis • Sequence of reactions that converts glucose into pyruvate • Relatively small amount of energy produced • Glycolysis reactions occur in cytoplasm • Does not require oxygen Lactate (anaerobic) Glucose → 2 Pyruvate Acetyl-CoA (TCA cycle)

19. Glycolysis Glucose + 2 ADP + 2 Pi 2 Pyruvate + 2 ATP + 2 H2O

20. First Reaction of Glycolysis Traps glucose in cells (irreversible in muscle cells)

21. Glycolysis - Summary Glucose (6C) 2 ATP 4 ADP 2 ADP 4 ATP 2 NAD 2 NADH + H 2 Pyruvate (3C)

22. Pyruvate Metabolism • Three fates of pyruvate: • Conversion to lactate (anaerobic) • Conversion to alanine (amino acid) • Entry into the TCA cycle via pyruvate dehydrogenase pathway (create ATP)

23. Pyruvate Metabolism • Three fates of pyruvate: • Conversion to lactate (anaerobic) • Conversion to alanine (amino acid) • Entry into the TCA cycle via pyruvate dehydrogenase pathway

24. Anaerobic Metabolism of Pyruvate to Lactate • Problem: • During glycolysis, NADH is formed from NAD+ • Without O2, NADH cannot be oxidized to NAD+ • No more NAD+ • All converted to NADH • Without NAD+, glycolysis stops…

25. Anaerobic Metabolism of Pyruvate • Solution: • Turn NADH back to NAD+ by making lactate (lactic acid) (reduced) (oxidized) (oxidized) (reduced)

26. Anaerobic Metabolism of Pyruvate • ATP yield • Two ATPs (net) are produced during the anaerobic breakdown of one glucose • The 2 NADHs are used to reduce 2 pyruvate to 2 lactate • Reaction is fast and doesn’t require oxygen

27. Pyruvate Metabolism - Anaerobic Lactate Dehydrogenase Pyruvate Lactate NADH NAD+ • Lactate can be transported by blood to liver and used in gluconeogenesis

28. Cori Cycle Lactate is converted to pyruvate in the liver

29. Pyruvate Metabolism • Three fates of pyruvate: • Conversion to lactate (anaerobic) • Conversion to alanine (amino acid) • Entry into the TCA cycle via pyruvate dehydrogenase pathway

30. Pyruvate metabolism • Convert to alanine and export to blood Keto acid Amino acid

31. Pyruvate Metabolism • Three fates of pyruvate: • Conversion to lactate (anaerobic) • Conversion to alanine (amino acid) • Entry into the TCA cycle via pyruvate dehydrogenase pathway

32. Pyruvate Dehydrogenase Complex (PDH) • Prepares pyruvate to enter the TCA cycle Aerobic Conditions Electron Transport Chain TCA Cycle

33. PDH - Summary Pyruvate 2 NAD 2 NADH + H CO2 Acetyl CoA

34. TCA Cycle • In aerobic conditions TCA cycle links pyruvate to oxidative phosphorylation • Occurs in mitochondria • Generates 90% of energy obtained from feed • Oxidize acetyl-CoA to CO2 and capture potential energy as NADH (or FADH2) and some ATP • Includes metabolism of carbohydrate, protein, and fat

36. TCA Cycle - Summary Acetyl CoA 3 NAD 3 NADH + H 2 CO2 1 FAD 1 FADH2 1 ADP 1 ATP

37. Oxidative Phosphorylation and the Electron Transport System • Requires coenzymes (NAD and FADH) as H+ carriers and consumes oxygen • Key reactions take place in the electron transport system (ETS) • Cytochromes of the ETS pass H2’s to oxygen, forming water

38. Oxidation and Electron Transport • Oxidation of nutrients releases stored energy • Feed donates H+ • H+’s transferred to co-enzymes NAD+ + 2H+ + 2e- NADH + H+ FAD + 2H+ + 2e- FADH2

39. So, What Goes to the ETS??? From each molecule of glucose entering glycolysis: • From glycolysis: 2 NADH • From the TCA preparation step (pyruvate to acetyl-CoA): 2 NADH • From TCA cycle (TCA) : 6 NADH and 2 FADH2 TOTAL: 10 NADH + 2 FADH2

40. Electron Transport Chain • NADH + H+ and FADH2 enter ETC • Travel through complexes I – IV • H+ flow through ETC and eventually attach to O2 forming water NADH + H+ 3 ATP FADH2 2 ATP

41. Electron Transport Chain

42. Total ATP from Glucose • Anaerobic glycolysis – 2 ATP + 2 NADH • Aerobic metabolism – glycolysis + TCA 31 ATP from 1 glucose molecule

43. Volatile Fatty Acids • Produced by bacteria in the fermentation of pyruvate • Three major VFAs • Acetate • Energy source and for fatty acid synthesis • Propionate • Used to make glucose through gluconeogenesis • Butyrate • Energy source and for fatty acid synthesis • Some use and metabolism (alterations) by rumen wall and liver before being available to other tissues

44. Use of VFA for Energy • Enter TCA cycle to be oxidized • Acetic acid • Yields 10 ATP • Propionic acid • Yields 18 ATP • Butyric acid • Yields 27 ATP • Little butyrate enters blood

45. Utilization of VFA in Metabolism Acetate Energy Carbon source for fatty acids Adipose Mammary gland Not used for net synthesis of glucose Propionate Energy Primary precursor for glucose synthesis Butyrate Energy Carbon source for fatty acids - mammary

46. Effect of VFA on Endocrine System • Propionate • Increases blood glucose • Stimulates release of insulin • Butyrate • Not used for synthesis of glucose • Stimulates release of insulin • Stimulates release of glucagon • Increases blood glucose • Acetate • Not used for synthesis of glucose • Does not stimulate release of insulin • Glucose • Stimulates release of insulin

47. A BRIEF INTERLUDE…

48. Need More Energy (More ATP)?? • Working animals • Horses, dogs, dairy cattle, hummingbirds! • Increase carbon to oxidize • Increased gut size relative to body size • Increased feed intake • Increased digestive enzyme production • Increased ability to process nutrients • Increased liver size and blood flow to liver • Increased ability to excrete waste products • Increased kidney size, glomerular filtration rate • Increased ability to deliver oxygen to tissues and get rid of carbon dioxide • Lung size and efficiency increases • Heart size increases and cardiac output increases • Increase capillary density • Increased ability to oxidize small carbon chains • Increased numbers of mitochondria in cells • Locate mitochondria closer to cell walls (oxygen is lipid-soluble)

49. Hummingbirds • Lung oxygen diffusing ability 8.5 times greater than mammals of similar body size • Heart is 2 times larger than predicted for body size • Cardiac output is 5 times the body mass per minute • Capillary density up to 6 times greater than expected

50. Rate of ATP Production(Fastest to Slowest) • Substrate-level phosphorylation • Phosphocreatine + ADP Creatine + ATP • Anaerobic glycolysis • Glucose Pyruvate Lactate • Aerobic carbohydrate metabolism • Glucose Pyruvate CO2 and H2O • Aerobic lipid metabolism • Fatty Acid Acetate CO2 and H2O