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5.) Carbohydrate metabolism Part 1

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  1. Front
    Glycolysis
    Back
    Cytosolic pathway that converts glucose to pyruvate and produces ATP
  2. Front
    Location of glycolysis
    Back
    Cytosol
  3. Front
    Tissues in which glycolysis occurs
    Back
    All human tissues
  4. Front
    Importance of glycolysis
    Back
    Fundamental source of metabolic energy
  5. Front
    Two phases of glycolysis
    Back
    Energy investment phase and energy generation phase
  6. Front
    Net result of glycolysis to pyruvate per glucose
    Back
    2 ATP, 2 NADH, and 2 pyruvate
  7. Front
    Fate of pyruvate when oxygen is adequate and mitochondria are present
    Back
    Pyruvate is further oxidized
  8. Front
    Fate of pyruvate when oxygen is lacking or in cells without mitochondria
    Back
    Pyruvate is reduced to lactate
  9. Front
    Cells without mitochondria that reduce pyruvate to lactate
    Back
    Erythrocytes
  10. Front
    GLUT transporter function
    Back
    Mediate facilitated diffusion of sugars down a concentration gradient without direct ATP use
  11. Front
    Energy requirement of GLUT transport
    Back
    Does not require ATP directly
  12. Front
    High-yield GLUTs mainly involved in glucose uptake from blood
    Back
    GLUT-1, GLUT-3, and GLUT-4
  13. Front
    GLUT transporter in liver and kidney that can move glucose into or out of cells
    Back
    GLUT-2
  14. Front
    Main sugar transported by GLUT-5
    Back
    Fructose
  15. Front
    Why glucose-6-phosphate is trapped in the cell
    Back
    It cannot diffuse across membranes because it is not a substrate for glucose transporters
  16. Front
    GLUT-1
    Back
    High-affinity glucose transporter important for basal glucose uptake
  17. Front
    GLUT-2
    Back
    Transporter in liver involved in bidirectional glucose movement depending on blood glucose level
  18. Front
    When GLUT-2 moves glucose into cells
    Back
    When blood glucose is high
  19. Front
    When GLUT-2 moves glucose out of cells
    Back
    When blood glucose is low
  20. Front
    High-yield lecture association for GLUT-2
    Back
    Liver glucokinase regulation diagram shows GLUT-2 bringing glucose into hepatocytes
  21. Front
    GLUT-3
    Back
    High-affinity transporter for tissues that need efficient glucose uptake
  22. Front
    GLUT-4
    Back
    Insulin-responsive transporter important in insulin-sensitive tissues
  23. Front
    GLUT-5
    Back
    Main transporter for fructose, especially important in the small intestine
  24. Front
    GLUT vs SGLT
    Back
    GLUT uses facilitated diffusion without direct ATP use, whereas SGLT uses sodium-dependent secondary active transport
  25. Front
    SGLT
    Back
    Na+-dependent glucose cotransport using secondary active transport
  26. Front
    Sites where SGLT occurs according to Lippincott
    Back
    Intestinal epithelial cells, renal tubules, and choroid plexus
  27. Front
    Pathway summarized by glycolysis
    Back
    Glucose → 2 pyruvate
  28. Front
    What glycolysis provides
    Back
    ATP directly by substrate-level phosphorylation and, under aerobic conditions, more ATP indirectly through oxidation of NADH
  29. Front
    Tissues that depend heavily or completely on glycolysis
    Back
    Brain, erythrocytes, spermatozoa, and renal medulla
  30. Front
    Order of glycolysis intermediates
    Back
    Glucose → glucose-6-phosphate → fructose-6-phosphate → fructose-1,6-bisphosphate → dihydroxyacetone phosphate → glyceraldehyde-3-phosphate → 1,3-bisphosphoglycerate → 3-phosphoglycerate → 2-phosphoglycerate → phosphoenolpyruvate → pyruvate
  31. Front
    Step 1 enzyme of glycolysis
    Back
    Hexokinase or glucokinase
  32. Front
    Step 1 reaction of glycolysis
    Back
    Glucose → glucose-6-phosphate using ATP
  33. Front
    Type of reaction in step 1 of glycolysis
    Back
    Phosphorylation
  34. Front
    Why phosphorylation of glucose is important
    Back
    It traps glucose in the cell because glucose-6-phosphate is not transported by glucose transporters
  35. Front
    Reversibility of step 1 of glycolysis
    Back
    Irreversible
  36. Front
    Step 2 enzyme of glycolysis
    Back
    Phosphohexose isomerase
  37. Front
    Step 2 reaction of glycolysis
    Back
    Glucose-6-phosphate → fructose-6-phosphate
  38. Front
    Type of reaction in step 2 of glycolysis
    Back
    Isomerization
  39. Front
    Structural change in step 2 of glycolysis
    Back
    Aldose form becomes ketose form
  40. Front
    Step 3 enzyme of glycolysis
    Back
    Phosphofructokinase-1 (PFK-1)
  41. Front
    Step 3 reaction of glycolysis
    Back
    Fructose-6-phosphate → fructose-1,6-bisphosphate using ATP
  42. Front
    Type of reaction in step 3 of glycolysis
    Back
    Phosphorylation
  43. Front
    Most important regulatory step of glycolysis
    Back
    PFK-1 reaction
  44. Front
    Reversibility of PFK-1 reaction
    Back
    Irreversible
  45. Front
    Step 4 enzyme of glycolysis
    Back
    Aldolase
  46. Front
    Step 4 reaction of glycolysis
    Back
    Fructose-1,6-bisphosphate → DHAP + GAP
  47. Front
    Type of reaction in step 4 of glycolysis
    Back
    Cleavage reaction
  48. Front
    Carbon change in the aldolase reaction
    Back
    6-carbon sugar is split into two 3-carbon molecules
  49. Front
    Step 5 enzyme of glycolysis
    Back
    Triose phosphate isomerase
  50. Front
    Step 5 reaction of glycolysis
    Back
    DHAP ⇌ GAP
  51. Front
    Why DHAP must be converted to GAP
    Back
    Only GAP continues directly through glycolysis
  52. Front
    Net result after triose phosphate isomerase from one glucose
    Back
    2 GAP molecules move forward
  53. Front
    Step 6 enzyme of glycolysis
    Back
    Glyceraldehyde-3-phosphate dehydrogenase
  54. Front
    Step 6 reaction of glycolysis
    Back
    GAP → 1,3-BPG
  55. Front
    Type of reaction in step 6 of glycolysis
    Back
    First oxidation-reduction reaction of glycolysis
  56. Front
    Cofactor change in step 6 of glycolysis
    Back
    NAD+ is reduced to NADH
  57. Front
    Other change in step 6 of glycolysis
    Back
    Inorganic phosphate is added to form 1,3-BPG
  58. Front
    Nature of 1,3-BPG
    Back
    High-energy intermediate
  59. Front
    Why NAD+ regeneration is essential for glycolysis
    Back
    Glycolysis can continue only if NADH formed in step 6 is reoxidized back to NAD+
  60. Front
    Step 7 enzyme of glycolysis
    Back
    Phosphoglycerate kinase
  61. Front
    Step 7 reaction of glycolysis
    Back
    1,3-BPG → 3-phosphoglycerate with ATP formation
  62. Front
    Type of reaction in step 7 of glycolysis
    Back
    First substrate-level phosphorylation
  63. Front
    Meaning of substrate-level phosphorylation in glycolysis
    Back
    High-energy phosphate is transferred directly from a substrate to ADP to make ATP
  64. Front
    ATP yield from step 7 per glucose
    Back
    2 ATP total per glucose
  65. Front
    Step 8 enzyme of glycolysis
    Back
    Phosphoglycerate mutase
  66. Front
    Step 8 reaction of glycolysis
    Back
    3-phosphoglycerate → 2-phosphoglycerate
  67. Front
    Change in step 8 of glycolysis
    Back
    Phosphate shifts from carbon 3 to carbon 2
  68. Front
    Reversibility of step 8 of glycolysis
    Back
    Reversible
  69. Front
    Step 9 enzyme of glycolysis
    Back
    Enolase
  70. Front
    Step 9 reaction of glycolysis
    Back
    2-phosphoglycerate → phosphoenolpyruvate
  71. Front
    Type of reaction in step 9 of glycolysis
    Back
    Dehydration
  72. Front
    Product of enolase reaction
    Back
    Phosphoenolpyruvate (PEP)
  73. Front
    Property of PEP
    Back
    It has a very high-energy phosphate bond
  74. Front
    Step 10 enzyme of glycolysis
    Back
    Pyruvate kinase
  75. Front
    Step 10 reaction of glycolysis
    Back
    PEP → pyruvate with ATP formation
  76. Front
    Type of reaction in step 10 of glycolysis
    Back
    Second substrate-level phosphorylation
  77. Front
    Phosphate transfer in the pyruvate kinase reaction
    Back
    Phosphate from PEP is transferred to ADP
  78. Front
    Reversibility of pyruvate kinase reaction
    Back
    Irreversible
  79. Front
    ATP yield from step 10 per glucose
    Back
    2 ATP total per glucose
  80. Front
    Three irreversible glycolysis reactions
    Back
    Hexokinase or glucokinase, PFK-1, and pyruvate kinase
  81. Front
    Why the irreversible glycolysis reactions are important
    Back
    They are the major regulatory points
  82. Front
    Substrate-level phosphorylation reactions in glycolysis
    Back
    1,3-BPG → 3-phosphoglycerate by phosphoglycerate kinase and PEP → pyruvate by pyruvate kinase
  83. Front
    Why substrate-level phosphorylation reactions are important
    Back
    ATP is made directly from a high-energy substrate rather than through the electron transport chain
  84. Front
    ATP used in the investment phase of glycolysis
    Back
    2 ATP
  85. Front
    Steps that consume ATP in glycolysis
    Back
    Glucose → G6P and F6P → F1,6BP
  86. Front
    ATP produced in the generation phase of glycolysis
    Back
    4 ATP total
  87. Front
    Sources of ATP in the generation phase of glycolysis
    Back
    2 ATP from phosphoglycerate kinase and 2 ATP from pyruvate kinase
  88. Front
    Net energy yield of glycolysis per glucose
    Back
    2 ATP, 2 NADH, and 2 pyruvate
  89. Front
    Hexokinases I–III
    Back
    Glucose-phosphorylating enzymes in various tissues with low Km, high affinity, and inhibition by G6P
  90. Front
    Location of hexokinases I–III
    Back
    Various tissues
  91. Front
    Km of hexokinase
    Back
    Low Km
  92. Front
    Affinity of hexokinase for glucose
    Back
    High affinity
  93. Front
    Regulation of hexokinase I–III
    Back
    Inhibited by glucose-6-phosphate
  94. Front
    Functional goal of hexokinase
    Back
    Use glucose efficiently even when glucose concentration is low
  95. Front
    Glucokinase
    Back
    Hexokinase IV found in liver and pancreatic β cells
  96. Front
    Location of glucokinase
    Back
    Liver and pancreatic β cells
  97. Front
    Km of glucokinase
    Back
    High Km
  98. Front
    Affinity of glucokinase for glucose
    Back
    Lower affinity than hexokinase
  99. Front
    Regulation of glucokinase by G6P
    Back
    Not inhibited by glucose-6-phosphate
  100. Front
    Role of glucokinase in the liver
    Back
    Helps handle excess glucose
  101. Front
    Role of glucokinase in pancreatic β cells
    Back
    Acts as a glucose sensor
  102. Front
    High-yield hexokinase vs glucokinase distinction
    Back
    Hexokinase works well at low glucose, whereas glucokinase becomes more important when glucose is high
  103. Front
    Regulation of liver glucokinase activity
    Back
    Regulated by translocation between cytoplasm and nucleus
  104. Front
    Effect of glucose on liver glucokinase translocation
    Back
    Promotes translocation from the nucleus
  105. Front
    Effect of fructose-6-phosphate on liver glucokinase
    Back
    Promotes translocation of glucokinase to the nucleus
  106. Front
    Effect of fructose-1-phosphate on liver glucokinase sequestration
    Back
    Inhibits glucokinase sequestration in the nucleus and can stimulate hepatic glucose metabolism
  107. Front
    Key allosteric glycolytic enzymes in the lecture
    Back
    Hexokinase, PFK-1, and pyruvate kinase
  108. Front
    Types of glycolytic regulation
    Back
    Allosteric effectors and, for some enzymes, covalent modification
  109. Front
    Most important regulatory enzyme of glycolysis
    Back
    PFK-1
  110. Front
    Activators of PFK-1
    Back
    AMP and fructose-2,6-bisphosphate
  111. Front
    Inhibitors of PFK-1
    Back
    ATP, citrate, and H+
  112. Front
    Meaning of AMP activation of PFK-1
    Back
    Low-energy state turns glycolysis on
  113. Front
    Meaning of ATP inhibition of PFK-1
    Back
    High-energy state turns glycolysis off
  114. Front
    Important liver regulator of PFK-1
    Back
    Fructose-2,6-bisphosphate strongly stimulates PFK-1
  115. Front
    Allosteric activator of pyruvate kinase
    Back
    Fructose-1,6-bisphosphate
  116. Front
    Type of pyruvate kinase activation by fructose-1,6-bisphosphate
    Back
    Feed-forward activation
  117. Front
    Allosteric inhibitor of pyruvate kinase
    Back
    ATP
  118. Front
    Covalent regulation of hepatic pyruvate kinase
    Back
    Phosphorylation by cAMP-dependent protein kinase (PKA) inactivates it
  119. Front
    Hormonal state associated with hepatic pyruvate kinase phosphorylation
    Back
    High glucagon and low blood glucose
  120. Front
    Very high-yield hepatic pyruvate kinase fact
    Back
    During fasting, hepatic pyruvate kinase is turned off by phosphorylation
  121. Front
    Key regulatory point for hexokinase I–III
    Back
    Inhibition by G6P
  122. Front
    End product of aerobic glycolysis
    Back
    Pyruvate
  123. Front
    Net yield of glycolysis itself under aerobic conditions
    Back
    2 ATP and 2 NADH
  124. Front
    Why cytosolic NADH needs shuttle systems
    Back
    Cytosolic NADH cannot cross the inner mitochondrial membrane directly
  125. Front
    Shuttle systems for cytosolic NADH
    Back
    Glycerol-phosphate shuttle and malate-aspartate shuttle
  126. Front
    Fate of pyruvate after aerobic glycolysis
    Back
    Can be converted to acetyl-CoA and fully oxidized
  127. Front
    Aerobic energy balance given in the lecture
    Back
    2 ATP from glycolysis plus 2 NADH yielding 3 to 5 ATP depending on shuttle, followed by much more ATP from pyruvate oxidation and TCA
  128. Front
    End product of anaerobic glycolysis
    Back
    Lactate
  129. Front
    Purpose of lactate formation in anaerobic glycolysis
    Back
    Regenerates NAD+ from NADH so glycolysis can continue
  130. Front
    Net yield of anaerobic glycolysis per glucose
    Back
    2 ATP and 2 lactate with no net NADH accumulation
  131. Front
    Tissues important for anaerobic glycolysis
    Back
    Erythrocytes, kidney medulla, lens or eye, and skeletal muscle during hypoxia or intense exercise
  132. Front
    Why erythrocytes always rely on anaerobic glycolysis
    Back
    They lack mitochondria
  133. Front
    What happens when lactate production rises greatly
    Back
    Blood lactate can increase
  134. Front
    Causes of elevated lactate listed in the lecture
    Back
    Intense exercise, hypoxia, CO poisoning, respiratory chain defects, Krebs cycle defects, and alcohol in large quantities
  135. Front
    Definition of lactic acidosis in the lecture
    Back
    Lactate greater than 5 mM
  136. Front
    Aerobic glycolysis integrated summary
    Back
    End product is pyruvate, NADH is reoxidized using mitochondrial shuttles and the ETC, and net glycolysis gives 2 ATP plus 2 NADH
  137. Front
    Anaerobic glycolysis integrated summary
    Back
    End product is lactate, NADH is reoxidized by lactate dehydrogenase, net yield is 2 ATP only, and it is important in RBCs and hypoxic tissues
  138. Front
    High-yield location fact for glycolysis
    Back
    Glycolysis is cytosolic
  139. Front
    High-yield list of irreversible glycolysis steps
    Back
    Hexokinase or glucokinase, PFK-1, and pyruvate kinase
  140. Front
    High-yield list of substrate-level phosphorylation steps in glycolysis
    Back
    Phosphoglycerate kinase and pyruvate kinase
  141. Front
    High-yield main regulatory step of glycolysis
    Back
    PFK-1
  142. Front
    High-yield hexokinase summary
    Back
    Low Km, inhibited by G6P, and found in most tissues
  143. Front
    High-yield glucokinase summary
    Back
    High Km, not inhibited by G6P, and found in liver and β-cells
  144. Front
    Why RBCs depend on glycolysis
    Back
    They lack mitochondria
  145. Front
    Why NAD+ regeneration is essential for glycolysis
    Back
    Because glyceraldehyde-3-phosphate dehydrogenase requires NAD+

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