Metabolism of Carbohydrates

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Metabolism of Carbohydrates

  1. 1. Carbohydrate Metabolism
  2. 2. An Overview of Metabolism
  3. 3. Adenosine Tri-Phosphate (ATP)  Link between energy releasing and energy requiring mechanisms  “rechargeable battery” ADP + P + Energy ATP
  4. 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. 5.  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 Metabolism
  6. 6.  Performance of structural maintenance and repairs  Support of growth  Production of secretions  Building of nutrient reserves Anabolism
  7. 7.  Breakdown of nutrients to provide energy (in the form of ATP) for body processes  Nutrients directly absorbed  Stored nutrients Catabolism
  8. 8.  Cells provide small organic molecules to mitochondria  Mitochondria produce ATP used to perform cellular functions Cells and Mitochondria
  9. 9. Metabolism of Carbohydrates
  10. 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. 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. 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 Synthesis and breakdown occur at all times regardless of state... The relative rates of synthesis and breakdown change
  13. 13. High Blood Glucose Glucose absorbed Insulin Pancreas Muscle Adipose Cells Glycogen Glucose absorbed Glucose absorbed immediately after eating a meal…
  14. 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. 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. 16. Glucose Utilization Glucose PyruvateRibose-5-phosphate Glycogen Energy Stores Pentose Phosphate Pathway Glycolysis Adipose
  17. 17. Glucose Utilization Glucose PyruvateRibose-5-phosphate Glycogen Energy Stores Pentose Phosphate Pathway Glycolysis Adipose
  18. 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 Glucose → 2 Pyruvate Lactate (anaerobic) Acetyl-CoA (TCA cycle)
  19. 19. Glycolysis Glucose + 2 ADP + 2 Pi 2 Pyruvate + 2 ATP + 2 H2O
  20. 20. First Reaction of Glycolysis Traps glucose in cells (irreversible in muscle cells)
  21. 21. Glycolysis - Summary Glucose (6C) 2 Pyruvate (3C) 2 ATP 2 ADP 4 ADP 4 ATP 2 NAD 2 NADH + H
  22. 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. 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. 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. 25. Anaerobic Metabolism of Pyruvate  Solution:  Turn NADH back to NAD+ by making lactate (lactic acid) COO– C O CH3 COO– HC OH CH3 LactatePyruvate Lactate dehydrogenase NADH+H+ NAD+ (oxidized) (reduced) (oxidized)(reduced)
  26. 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. 27. Pyruvate Metabolism - Anaerobic Pyruvate Lactate NADH NAD+ Lactate Dehydrogenase  Lactate can be transported by blood to liver and used in gluconeogenesis
  28. 28. Cori Cycle Lactate is converted to pyruvate in the liver
  29. 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. 30. Pyruvate metabolism  Convert to alanine and export to blood COO– C O CH3 COO– HC NH3 + CH3 Alanineaminotransferase (AAT) AlaninePyruvate Glutamate α-Ketoglutarate Keto acid Amino acid
  31. 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. 32. Pyruvate Dehydrogenase Complex (PDH)  Prepares pyruvate to enter the TCA cycle Electron Transport Chain TCA Cycle Aerobic Conditions
  33. 33. PDH - Summary Pyruvate Acetyl CoA 2 NAD 2 NADH + H CO2
  34. 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
  35. 35. TCA Cycle - Summary Acetyl CoA 3 NAD 3 NADH + H 1 FAD 1 FADH2 1 ADP 1 ATP 2 CO2
  36. 36.  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 Oxidative Phosphorylation and the Electron Transport System
  37. 37. 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
  38. 38. So, What Goes to the ETS??? From each molecule of glucose entering glycolysis: 1. From glycolysis: 2 NADH 2. From the TCA preparation step (pyruvate to acetyl-CoA): 2 NADH 3. From TCA cycle (TCA) : 6 NADH and 2 FADH2 TOTAL: 10 NADH + 2 FADH2
  39. 39. 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
  40. 40. Electron Transport Chain
  41. 41. Total ATP from Glucose  Anaerobic glycolysis – 2 ATP + 2 NADH  Aerobic metabolism – glycolysis + TCA 31 ATP from 1 glucose molecule
  42. 42. 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
  43. 43. 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
  44. 44. 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
  45. 45. 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
  46. 46. A BRIEF INTERLUDE…
  47. 47. 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)
  48. 48. 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
  49. 49. 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
  50. 50. Potential Amount of Energy Produced (Capacity for ATP Production)  Aerobic lipid metabolism  Fatty Acid Acetate CO2 and H2O  Aerobic carbohydrate metabolism  Glucose Pyruvate CO2 and H2O  Anaerobic glycolysis  Glucose Pyruvate Lactate  Substrate-level phosphorylation  Phosphocreatine + ADP Creatine + ATP
  51. 51. Glucose Utilization Glucose PyruvateRibose-5-phosphate Glycogen Energy Stores Pentose Phosphate Pathway Glycolysis Adipose
  52. 52. Pentose Phosphate Pathway  Secondary metabolism of glucose  Produces NADPH  Similar to NADH  Required for fatty acid synthesis  Generates essential pentoses  Ribose  Used for synthesis of nucleic acids
  53. 53. Glucose Utilization Glucose PyruvateRibose-5-phosphate Glycogen Energy Stores Pentose Phosphate Pathway Glycolysis Adipose
  54. 54. Energy Storage  Energy from excess carbohydrates (glucose) stored as lipids in adipose tissue  Acetyl-CoA (from TCA cycle) shunted to fatty acid synthesis in times of energy excess  Determined by ATP:ADP ratios  High ATP, acetyl-CoA goes to fatty acid synthesis  Low ATP, acetyl CoA enters TCA cycle to generate MORE ATP
  55. 55. Glucose Utilization Glucose PyruvateRibose-5-phosphate Glycogen Energy Stores Pentose Phosphate Pathway Glycolysis Adipose Glycogenesis
  56. 56.  Liver  7–10% of wet weight  Use glycogen to export glucose to the bloodstream when blood sugar is low  Glycogen stores are depleted after approximately 24 hrs of fasting (in humans)  De novo synthesis of glucose for glycogen Glycogenesi s
  57. 57. Glycogenesis  Skeletal muscle  1% of wet weight  More muscle than liver, therefore more glycogen in muscle, overall  Use glycogen (i.e., glucose) for energy only (no export of glucose to blood)  Use already-made glucose for synthesis of glycogen
  58. 58. 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 Synthesis and breakdown occur at all times regardless of state... The relative rates of synthesis and breakdown change
  59. 59. Fasting Situation in Non-Ruminants  Where does required glucose come from? Glycogenolysis Lipolysis Proteolysis  Breakdown or mobilization of glycogen stored by glucagon  Glucagon - hormone secreted by pancreas during times of fasting  Mobilization of fat stores stimulated by glucagon and epinephrine  Triglyceride = glycerol + 3 free fatty acids  Glycerol can be used as a glucose precursor  The breakdown of muscle protein with release of amino acids  Alanine can be used as a glucose precursor
  60. 60. Low Blood Glucose Proteins Broken Down Insulin Pancreas Muscle Adipose Cells Glycogen Glycerol, fatty acids released Glucose released In a fasted state, substrates for glucose synthesis (gluconeogenesis) are released from “storage”…
  61. 61. Gluconeogenesis  Necessary process  Glucose is an important fuel  Central nervous system  Red blood cells  Not simply a reversal of glycolysis  Insulin and glucagon are primary regulators
  62. 62. Gluconeogenesis  Vital for certain animals  Ruminant species and other pre-gastric fermenters  Convert carbohydrate to VFA in rumen  Little glucose absorbed from small intestine  VFA can not fuel CNS and RBC  Feline species  Diet consists primarily of fat and protein  Little to no glucose absorbed  Glucose conservation and gluconeogenesis are vital to survival
  63. 63. Gluconeogenesis  Synthesis of glucose from non-carbohydrate precursors during fasting in monogastrics  Glycerol  Amino acids  Lactate  Pyruvate  Propionate There is no glucose synthesis from fatty acids Supply carbon skeleton
  64. 64. Carbohydrate Comparison  Primary energy substrate  Primary substrate for fat synthesis  Extent of glucose absorption from gut  MOST monogastrics = glucose  Ruminant/pre-gastric fermenters = VFA  MOST monogastrics = glucose  Ruminant = acetate  MOST monogastrics = extensive  Ruminant = little to none
  65. 65. Carbohydrate Comparison  Cellular demand for glucose  Importance of gluconeogenesis  Nonruminant = high  Ruminant = high  MOST monogastrics = less important  Ruminant = very important

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