BioChem Glycolysis (15)

  1. What is the net chemical equation for the reactions of anaerobic glycolysis?
    • Glucose + 2 ADP + 2 Pi -->
    • 2 Lactate + 2ATP + 2 H2O

    lactate = lactic acid
  2. Which cell type in the human body relies ONLY on glycolysis as a source of ATP?
    Erythrocytes (red blood cells) only because they don't have mitochondria
  3. Hemolytic anemias
    • result of genetic defects that lead to enzyme deficiencies or instabilities
    • condition in which RBCs are destroyed and removed from the bloodstream before their normal lifespan is over
  4. Which enzyme is most frequently deficient in hemolytic anemias?
    pyruvate kinase
  5. What is the major source of ATP in skeletal muscle at rest? During exercise?
    • At rest: Oxidative metabolism
    • During exercise: both oxidative phosphorylation and glycolysis
  6. The net gain of glycolysis:
    • 2 moles of ATP per mole of glucose metabolized
    • * under ANAEROBIC conditions, the 2 pyruvates are reduced to 2 lactates
  7. In which cellular compartment does glycolysis occur?
    • cytoplasm
    • all the enzymes required for glycolysis are present in the cytoplasm
  8. What enzymes converts glucose to glucose-6-phosphate?
    • hexokinase: present in almost all cells
    • glucokinase: present only in brain, liver, pancreas, gut cells
  9. phosphohexose/phosphoglucose isomerase
    • enzyme functions in the 2nd step of glycolysis to convert glucose-6-phosphate --> ¬† ¬† ¬†fructose-6-phosphate
    • it's specific for glucose & fructose and the conversion reaction is readily reversible
  10. phosphofructokinase 1 (PFK 1)
    • converts Fructose-6-Phosphate --> Fructose-1,6-bisPhosphate
    • 3rd step in glycolysis, but the 1st that's committed uniquely to glycolysis
    • key regulation step
  11. the PFK 1 reaction is inhibited by ___ (3) but activated by ___ (4)
    • ATP, citrate & fatty acids inhibit the PFK 1 reaction
    • AMP, ADP & Pi activate the PFK 1 reaction
    • *at intracellular concentrations of these regulators, the reaction rate is only a small fraction of the potential maximal velocity for the amount of enzyme present*
  12. Which molecules are able to inhibit phosphofructokinase-1 (PFK-1)?
    ATP, citrate & fatty acids
  13. Which molecules are able to activate (relieve inhibition of) phosphofructokinase-1 (PFK-1)?
    ADP, AMP, and fructose-2,6-bisphosphate
  14. fructose-2,6-bisphosphate
    • physiologically important activator of PFK 1
    • synthesized only small amounts from fructose-6-phosphate by phosphofructokinase 2
  15. Both the PFK1 and PFK 2-catalyzed reactions are:
    • irreversible
    • they can, however be hydrolyzed back to fructose-6-phosphate + Pi with phosphatases
    • (fructose-1,6-bisphosphatase and fructose-2,6-bisphosphatase)
  16. What is the committed step in glycolysis?
    the phosphofructokinase-1 reaction (PFK1)
  17. What reaction does phosphofructokinase-2 (PFK-2) catalyze?
    Fructose-6-phosphate + ATP --> fructose-2,6-bisphosphate + ADP
  18. aldolase
    • enzyme that catalyzes
    • Fructose-1,6-bisPhosphate --> glyceraldehyde-3-phosphate + dihydroxyacetone-phosphate
  19. the aldolase reaction is:
    • Fructose-1,6-bisPhosphate --> glyceraldehyde-3-phosphate + dihydroxyacetone-phosphate
    • *part of the reaction where 6 carbon molecule becomes two 3 carbon molecules
  20. Which of the two products of the aldolase reaction is a direct glycolytic intermediate?
    • Glyceraldehyde-3-phosphate is the substrate for the next steps of glycolysis
    • the other product, Dihydroxyacetone-phosphate, must be isomerized into glyceraldehyde-3-phosphate to continue through glycolysis
  21. triosephosphate isomerase
    • reversibly isomerizes dihydroxyacetone-phosphate into glyceraldehyde-3-phosphate
    • takes the 2nd 3-carbon produced by PFK 1 and converts it so as to continue the process of glycolysis
  22. glyceraldehyde 3-phosphate dehydrogenase
    • catalyzes the reversible two step conversion of glyceraldehyde 3-phosphate --> 1,3-bisPhosphoglycerate first glyceraldehyde 3-phosphate is oxidized at carbon 1 (aldehyde converted into COOH) & NAD+ --> NADH (reduced)
    • the energy released drives the endergonic second reaction where Pi is transferred to the GAP intermediate to form 1,3-bisphosphoglycerate
  23. The reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase is an example of what two things coupled?
    it's an example of phosphorylation coupled to oxidation (oxidation is the thing that provides the energy for the subsequent phosphorylation)
  24. Which glycolytic enzyme catalyzes a reaction that yields NADH?
    • glyceraldehyde-3-phosphate dehydrogenase
    • oxidation of Carbon1 results in reduction of NAD+ --> NADH
  25. What's another name for glyceraldehyde-3-phosphate?
    fucking triose-phosphate
  26. negative cooperativity
    as ligands bind to an enzyme, the enzyme's affinity for the ligand will decrease
  27. Which glycolytic enzyme exhibits negative cooperativity?
    • glyceraldehyde-3-phosphate dehydrogenase
    • it can bind up to 4 NAD+ molecules that become harder to add after successive molecule binding
    • means the enzyme activity is buffered from changes in substrate concentration
    • enzyme resists losing NAD+ when glycolysis is at a high rate (eg. in anaerobic muscle)
    • enzyme keeps NAD+ when glycolysis is at a normal or low rate so the rate can be maintained
  28. How many NAD+ molecules can glyceraldehyde-3-phosphate dehydrogenase bind?
  29. Which glycolytic enzyme uses inorganic phosphate NOT ATP to phosphorylate its substrates?
    • glyceraldehyde-3-phosphate dehydrogenase
    • *very important!
  30. phosphoglycerate kinase
    • 1,3-bisphosphoglycerate --> 3-phosphoglycerate
    • reversibly transfers high energy phosphate group to ADP forming ATP
    • one ATP generated from each 1,3-bisphosphoglycerate (triose-phosphate) ==> the reaction generates 2 moles of ATP per original mole of glucose
  31. substrate-level phosphorylation
    the formation of ATP (or GTP) by the direct transfer of a phosphate group from a reactive metabolic intermediate to ADP (or GDP)
  32. phosphoglycerate mutase
    • 3-phosphoglycerate --> 2-phosphoglycerate
    • reversibly transfers its own phosphate to form the intermediate 2,3-bisPhosphoglycerate
    • the intermediate donates its 3-phosphate back to the enzyme releasing 2-phosphoglycerate
  33. enolase
    • 2-phosphoglycerate --> phosphoenolpyruvate
    • reversible reaction that involves the removal of water to make a HIGH energy phosphate bond
  34. What molecule strongly inhibits enolase?
  35. What type of a reaction does enolase catalyze?
  36. Which enzyme catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PEP)?
  37. pyruvate kinase
    • phosphoenolpyruvate (PEP) --> pyruvate [+ ATP]
    • reaction is irreversible
    • another key site of glycolysis regulation
  38. Pyruvate kinase is stimulated by what and inhibited by what?
    • fructose-1,6-bisphosphate stimulates pyruvate kinase (feed forward stimulation)
    • alanine, NADH, ATP, fatty acids, and succinyl-CoA inhibit pyruvate kinase (they're downstream products of further pathways)
  39. Liver, but not muscle, pyruvate kinase is INHIBITED by:
    phosphorylation stimulated by epinephrine or glucagon
  40. Which enzyme catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate and ATP?
    pyruvate kinase
  41. How many moles of ATP does pyruvate kinase generate per glucose molecule?
  42. Which molecules stimulate the activity of pyruvate kinase?
    • fructose-1,6-bisphosphate
    • this phenomenon is called feed-forward stimulation
  43. Which molecules are able to inhibit pyruvate kinase?
    Alanine, NADH, ATP, fatty acids, and succinyl-CoA
  44. lactate dehydrogenase
    • regenerates oxidized NAD+
    • under anaerobic conditions it transfers electrons from NADH to pyruvate, reducing pyruvate to lactate & regenerating NAD+
    • NAD+ regeneration is required if the cell is to continue with glycolysis under anaerobic conditions b/c NAD+ is a required cofactor for glyceraldehyde-3-phosphate dehydrogenase
  45. Most of the NAD+ in cells is synthesized from niacin (vitamin B3). However, a small amount of NAD+ may be synthesized from which amino acid?
  46. Red cells have lactate dehydrogenase primarily so that:
    they can regenerate NAD to keep glycolysis going [under anaerobic conditions]
  47. Pellagra
    • disease due to a deficiency of niacin
    • characterized by poor growth, weight loss, skin rash, diarrhea, & mental disturbances
  48. List the main symptoms of pellagra:
    the four D's: diarrhea, dementia, dermatitis and death
  49. What are two examples of how NAD+ can be used for oxidation?
    • The glyceraldehyde-3-phosphate dehydrogenase reaction
    • Alcohol dehydrogenase, which converts ethanol to acetaldehyde, is another
  50. What is an example of how NADH can be used for reduction?
    Lactate dehydrogenase reaction
  51. In which cell compartment do the reversible interconversions of lactate <--> alanine <--> pyruvate occur?
    the cytoplasm
  52. In which cell compartment do the irreversible conversions of pyruvate to oxaloacetate and acetyl-CoA occur?
  53. pyruvate is converted to lactate for:
    anaerobic respiration
  54. pyruvate is converted to oxaloacetate for:
    glucose synthesis
  55. pyruvate is converted to acetyl CoA for:
    oxidative metabolism or fatty acid synthesis
  56. pyruvate is converted to alanine for:
    protein synthesis because alanine is an amino acid...
  57. Which glycolytic enzymes catalyze irreversible reactions?
    • Hexokinase: glucose --> glucose-6-phosphate
    • phosphofructokinase-1 (PFK-1): F-6-P --> F-1,6-bisP
    • pyruvate kinase: phoshoenolpyruvate --> pyruvate
    • their rates are usually much slower than the maximal rates possible for the amount of enzyme present
    • under resting conditions they're inhibited; when energy needs increase, reaction rates can be increased a lot
    • *irreversible steps are the primary sites of regulation
  58. Which glycolytic enzymes are allosterically regulated?
    Hexokinase, phosphofructokinase-1 (PFK-1) & pyruvate kinase
  59. Hexokinase is inhibited by __________. Why?
    glucose-6-phosphate b/c G-6-P is it's product so it doesn't want to overproduce it's product
  60. Phosphofructokinase is activated by ____________ (2)and inhibited by ___________ (3)
    • activated: F-2,6-bisP, ADP, AMP
    • inhibited: ATP, Citrate, fatty acids (products down the line)
  61. Pyruvate kinase is activated by ____________ (2) and inhibited by ___________ (4) is
    • activated: F-1,6-bisP, F-2,6-bisP
    • inhibited: ATP, NADH, Alanine, fatty acids, SuccinylCoA(products down the line)
  62. Which glycolytic enzyme is regulated by phosphorylation?
    pyruvate kinase is inactivated by phosphorylation
  63. What induces glucokinase AND pyruvate kinase transcription?
    • a high carbohydrate diet and insulin
    • transcription of both is decreased in low carbohydrate diet, starvation
  64. The hormone insulin induces the synthesis of which glycolytic enzymes?
    Glucokinase and pyruvate kinase
  65. What is the net yield of ATP in the conversion of one glucose molecule to two pyruvates during glycolysis?
    TWO moles of net ATP are net produced per ONE mole of glucose
  66. Which glycolytic enzymes catalyze reactions that yield ATP?
    phosphoglycerate kinase & pyruvate kinase
  67. What can glucose-6-phosphate be used for besides its role as a glycolytic intermediate?
    • can be used to synthesize:
    • glycogen
    • polysaccharides
    • glycoproteins
    • pentoses (for nucleotide and nucleic acid biosynthesis)
  68. The pentose phosphate shunt produces NADPH and pentose sugars. Pentose sugars from this shunt may enter the glycolytic pathway as which glycolytic intermediate(s)?
    Fructose-6-phosphate and glyceraldehyde-3-phosphate
  69. What can dihydroxyacetone-phosphate be reduced to and later used for?
    it can be reduced to glycerol phosphate, which is a precursor for neutral fat & phospholipid biosynthesis
  70. Which glycolytic enzymes use ATP to phosphorylate their substrate, thereby producing ADP?
    hexokinase and phosphofructokinase-1 (PFK-1)
  71. What molecule inhibits hexokinase?
    2-deoxyglucose - competitively inhibits production of glucose-6-phosphate from glucose
  72. ______ can be synthesized from 3-phosphoglycerate
    • serine
    • an example of not always going back the way you came because serine is degraded by a dehydratease
  73. NAD+ is derived from which vitamin?
    Vitamin B3 (niacin)
  74. Pyruvate can be inter-converted with which amino acid?
    Alanine by by reversible transamination
  75. What can be made from 1,3 bisphosphoglycerate and what process does this product regulate!?
    • 2,3 bisphosphoglycerate can be made, and it regulates hemoglobin
    • this is 2,3-BPG! It's an allosteric effector that interacts with deoxygenated hemoglobin beta subunits & decreasing their affinity for oxygen, promoting oxygen to be released near tissues that need it most
  76. Which glycolytic intermediate(s) can be oxidized to acetyl-CoA, which is used for synthesis of fatty acids, cholesterol, steroid hormones and oxidative metabolism?
  77. Which toxic substance is able to inhibit hexokinase?
    • 2-deoxyglucose
    • hexokinase converts it to 2-deoxyglucose-6-phosphate
    • because this product's not a substrate for the hexose phosphate isomerase it accumulates and exerts feedback inhibition on hexokinase
  78. pentavalent arsenic
    • prevents the production of ATP by glyceraldehyde-3-phosphate dehydrogenase
    • it does not stop the process of glycolysis, it only prevents the net gain of ATP
  79. Which toxic substances can react with the sulfhydryl group of glyceraldehyde-3-phosphate dehydrogenase to block the glycolytic process altogether?
    mercury compounds and trivalent arsenicals
  80. Tauri's Disease
    • recessive metabolic disorder (phosphofructokinase deficiency/Glycogen storage disease type VII)
    • deficiency of the M subunit of the phosphofructokinase 1 enzyme impairs the ability of cells (eg. RBCs/skeletal muscle cells) to phosphorylate fructose-6-phosphate prior to its cleavage into glyceraldehyde-3-phosphate
    • this limits energy production & directly affects glycolysis
  81. How does the regulation of lactate dehydrogenase in skeletal muscle differ from that in cardiac muscle?
    • In skeletal muscle, if more pyruvate is produced than can enter the TCA cycle, pyruvate will be converted to lactate by lactate dehydrogenase
    • In the heart, rising pyruvate concentrations inhibit lactate dehydrogenase; this is because lactate is an acid that can cause muscle cramps in excess
    • pyruvate inhibition of lactate dehydrogenase in the heart has a protective effect on cardiac function
Card Set
BioChem Glycolysis (15)
Exam 2