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Gluconeogenesis

Tier 1 · #2 of 33 · highest yield · topic 3.6 — every high-yield fact from the book chapter, exam-ready.

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  1. Front
    Gluconeogenesis is the synthesis of glucose from what kind of precursors?
    Back
    Non-carbohydrate precursors
  2. Front
    Which organ performs the majority (~80%) of gluconeogenesis?
    Back
    The liver
  3. Front
    Besides the liver, which tissue carries out gluconeogenesis (up to ~20% of output)?
    Back
    The renal cortex ( kidney )
  4. Front
    Gluconeogenesis shares how many of its ten steps with glycolysis run in reverse?
    Back
    Seven of ten steps
  5. Front
    How many glycolytic reactions are irreversible and must be bypassed in gluconeogenesis?
    Back
    Three (requiring four bypass enzymes)
  6. Front
    What are the three major gluconeogenic substrates?
    Back
    Lactate , alanine , and glycerol
  7. Front
    Which gluconeogenic substrate is the most quantitatively important?
    Back
    Lactate
  8. Front
    The recycling loop in which muscle/erythrocyte lactate goes to the liver to be remade into glucose is called the ___.
    Back
    Cori cycle
  9. Front
    In the Cori cycle, how is lactate converted back to pyruvate in the liver?
    Back
    By lactate dehydrogenase
  10. Front
    Why do erythrocytes continuously feed lactate into the Cori cycle?
    Back
    They lack mitochondria , so they run on pure glycolysis
  11. Front
    Alanine reaches the liver from muscle via which cycle?
    Back
    The glucose-alanine cycle
  12. Front
    Which enzyme in the liver removes the amino group from alanine to regenerate pyruvate ?
    Back
    Alanine aminotransferase
  13. Front
    When alanine is deaminated in the liver , where does the amino group go?
    Back
    To urea synthesis
  14. Front
    Glycerol for gluconeogenesis comes from the hydrolysis of what, in which tissue?
    Back
    Triacylglycerols in adipose tissue
  15. Front
    Glycerol enters the gluconeogenic pathway as which triose phosphate intermediate?
    Back
    Dihydroxyacetone phosphate (DHAP)
  16. Front
    Glycerol is first phosphorylated to ___ before being oxidized to DHAP .
    Back
    Glycerol-3-phosphate
  17. Front
    What is the single most-tested fact: can acetyl-CoA be converted to glucose in animals?
    Back
    No — acetyl-CoA cannot be converted to glucose in animals
  18. Front
    Why can't acetyl-CoA yield net glucose ? (mechanistic reason)
    Back
    Its two carbons are lost as CO2 within one turn of the TCA cycle, giving no net oxaloacetate
  19. Front
    True/exam trap: even-chain fatty acid oxidation provides net carbon for glucose?
    Back
    No — it powers gluconeogenesis energetically but contributes zero net carbon to glucose
  20. Front
    Which narrow class of fatty acids CAN make a small net gluconeogenic contribution?
    Back
    Odd-chain fatty acids
  21. Front
    Odd-chain fatty acid oxidation yields which 3-carbon product that can become glucose ?
    Back
    Propionyl-CoA (→ succinyl-CoA → OAA )
  22. Front
    What are the four bypass enzymes of gluconeogenesis (in pathway order)?
    Back
    Pyruvate carboxylase , PEPCK , fructose-1,6-bisphosphatase , glucose-6-phosphatase
  23. Front
    Which three glycolytic enzymes catalyze the irreversible steps that gluconeogenesis must bypass?
    Back
    Hexokinase , PFK-1 , and pyruvate kinase
  24. Front
    Which bypass enzyme converts pyruvate to oxaloacetate ?
    Back
    Pyruvate carboxylase
  25. Front
    In which cellular compartment does pyruvate carboxylase operate?
    Back
    The mitochondria
  26. Front
    Which vitamin-derived prosthetic group (CO2 carrier) does pyruvate carboxylase require?
    Back
    Biotin (vitamin B7)
  27. Front
    How many ATP does pyruvate carboxylase consume per pyruvate ?
    Back
    One ATP
  28. Front
    Pyruvate carboxylase is allosterically activated by which molecule?
    Back
    Acetyl-CoA
  29. Front
    Without acetyl-CoA , what happens to pyruvate carboxylase activity?
    Back
    It is essentially silent/inactive
  30. Front
    Which bypass enzyme converts oxaloacetate to phosphoenolpyruvate (PEP) ?
    Back
    PEPCK (phosphoenolpyruvate carboxykinase)
  31. Front
    PEPCK consumes which high-energy nucleotide per reaction?
    Back
    One GTP
  32. Front
    In which compartment does PEPCK primarily operate?
    Back
    The cytoplasm/cytosol
  33. Front
    OAA cannot cross the inner mitochondrial membrane; how is it exported to the cytosol?
    Back
    It is reduced to malate , exported via the malate shuttle , then re-oxidized to OAA
  34. Front
    Re-oxidizing cytosolic malate to OAA produces what, needed for a later gluconeogenic step?
    Back
    Cytosolic NADH
  35. Front
    The cytosolic NADH from the malate shuttle is needed to reduce 1,3-bisphosphoglycerate to which product?
    Back
    Glyceraldehyde-3-phosphate (G3P)
  36. Front
    Which bypass enzyme hydrolyzes fructose-1,6-bisphosphate to fructose-6-phosphate ?
    Back
    Fructose-1,6-bisphosphatase (FBPase-1)
  37. Front
    Does the FBPase-1 reaction generate or consume ATP?
    Back
    Neither — it hydrolyzes the phosphate, releasing the bond energy as heat
  38. Front
    FBPase-1 is inhibited by which two signals (the same ones that activate PFK-1 )?
    Back
    AMP and fructose-2,6-bisphosphate
  39. Front
    FBPase-1 is allosterically activated by which molecule?
    Back
    Citrate
  40. Front
    Which bypass enzyme hydrolyzes glucose-6-phosphate to free glucose ?
    Back
    Glucose-6-phosphatase
  41. Front
    On which organelle membrane is glucose-6-phosphatase located?
    Back
    The inner face of the endoplasmic reticulum membrane
  42. Front
    Glucose-6-phosphatase is found ONLY in which two tissues?
    Back
    Liver and renal cortex
  43. Front
    Why can skeletal muscle NOT release free glucose into the blood?
    Back
    It lacks glucose-6-phosphatase , so its G6P stays trapped (and cannot cross the membrane )
  44. Front
    Deficiency of glucose-6-phosphatase causes which disease?
    Back
    Von Gierke disease ( Type Ia glycogen storage disease )
  45. Front
    What are the two hallmark clinical features of Von Gierke disease ?
    Back
    Severe fasting hypoglycemia and hepatomegaly
  46. Front
    What is the net energy cost to make one glucose from two pyruvates ?
    Back
    6 ATP equivalents plus 2 NADH
  47. Front
    In the 6 ATP cost, how many come from pyruvate carboxylase , PEPCK , and phosphoglycerate kinase respectively (per glucose)?
    Back
    2 ATP ( pyruvate carboxylase ) + 2 GTP ( PEPCK ) + 2 ATP ( phosphoglycerate kinase )
  48. Front
    Glycolysis nets how many ATP per glucose, versus the 6 ATP gluconeogenesis spends?
    Back
    2 ATP
  49. Front
    Which metabolic process supplies the energy (ATP) to fund gluconeogenesis during fasting?
    Back
    Hepatic fatty acid beta-oxidation
  50. Front
    Acetyl-CoA from fatty acid oxidation does two key things in gluconeogenesis — name them.
    Back
    Activates pyruvate carboxylase , and (via ATP it generates) powers the energy-requiring steps
  51. Front
    In the Cori cycle, how many ATP does the liver pay to recover each glucose , vs. ATP muscle gained making the lactate ?
    Back
    Liver pays 6 ATP; muscle gained only 2 ATP
  52. Front
    Which two hormones ACTIVATE hepatic gluconeogenesis?
    Back
    Glucagon and adrenaline (epinephrine)
  53. Front
    Which hormone SUPPRESSES gluconeogenesis?
    Back
    Insulin
  54. Front
    Glucagon signals through which second messenger and kinase to control gluconeogenesis?
    Back
    cAMP and protein kinase A (PKA)
  55. Front
    Glucagon -mediated phosphorylation inactivates which glycolytic enzyme, forcing PEP up toward glucose ?
    Back
    Pyruvate kinase
  56. Front
    At the transcriptional level, glucagon / adrenaline increase expression of which two gluconeogenic enzymes?
    Back
    PEPCK and glucose-6-phosphatase
  57. Front
    Which single allosteric molecule is the master switch toggling between glycolysis and gluconeogenesis in the liver?
    Back
    Fructose-2,6-bisphosphate (F2,6BP)
  58. Front
    Fructose-2,6-bisphosphate has what opposite effects on PFK-1 vs. FBPase-1 ?
    Back
    Activates PFK-1 (glycolysis); inhibits FBPase-1 (gluconeogenesis)
  59. Front
    When glucagon is high, what happens to F2,6BP levels and the direction of carbon flow?
    Back
    F2,6BP falls → PFK-1 slows , FBPase-1 opens → flow tilts toward glucose synthesis
  60. Front
    Is acetyl-CoA 's activation of pyruvate carboxylase hormonal or purely allosteric (and what does it sense)?
    Back
    Purely allosteric — a direct intramitochondrial sensor of the energy/fuel state
  61. Front
    Besides activating pyruvate carboxylase , acetyl-CoA inhibits which enzyme to keep pyruvate out of the TCA cycle?
    Back
    Pyruvate dehydrogenase
  62. Front
    In the liver, lactate dehydrogenase oxidizes lactate to pyruvate , producing what?
    Back
    Cytosolic NADH
  63. Front
    Which enzyme decarboxylates oxaloacetate to PEP , releasing CO2?
    Back
    PEPCK
  64. Front
    When insulin is high and blood glucose is abundant, what happens to F2,6BP levels and the direction of carbon flow?
    Back
    F2,6BP rises → PFK-1 is activated , FBPase-1 is inhibited → flow reverses toward glycolysis
  65. Front
    High insulin activates PFK-1 and inhibits FBPase-1 by changing the level of which single allosteric molecule?
    Back
    Fructose-2,6-bisphosphate (it rises)
  66. Front
    At the transcriptional level, insulin has what effect on the gluconeogenic enzymes PEPCK and glucose-6-phosphatase ?
    Back
    It suppresses (decreases) their expression
  67. Front
    Glucagon / adrenaline INCREASE expression of PEPCK and glucose-6-phosphatase ; which hormone does the reciprocal and DECREASES it?
    Back
    Insulin
  68. Front
    Roughly how much glucose does the brain consume every day, regardless of activity?
    Back
    ~120 grams of glucose per day
  69. Front
    After about how many hours of fasting is the liver 's glycogen largely spent (the trigger window for gluconeogenesis)?
    Back
    ~12 hours
  70. Front
    Reciprocal regulation of FBPase-1 and PFK-1 by F2,6BP /AMP ensures what about glycolysis and gluconeogenesis?
    Back
    They are never running simultaneously at full throttle
  71. Front
    Why does the cell route oxaloacetate out of the mitochondria as malate rather than as OAA itself?
    Back
    OAA cannot cross the inner mitochondrial membrane , but malate can (via the malate shuttle)
  72. Front
    Cytosolic NADH is specifically required for which gluconeogenic step?
    Back
    Reduction of 1,3-bisphosphoglycerate to glyceraldehyde-3-phosphate
  73. Front
    The conversion of pyruvate all the way to PEP ( pyruvate carboxylase + PEPCK ) costs how many ATP equivalents per pyruvate ?
    Back
    2 ATP equivalents (1 ATP + 1 GTP) per pyruvate — i.e. 4 per glucose
  74. Front
    OAA is shuttled out of the mitochondrion as malate via which specifically named shuttle?
    Back
    The malate-aspartate shuttle
  75. Front
    Fatty acids released from adipose alongside glycerol are oxidized in the liver to supply which three things for gluconeogenesis?
    Back
    ATP , NADH , and acetyl-CoA
  76. Front
    Gluconeogenesis is calibrated by two control arms — name the fast arm and the slow arm.
    Back
    Fast = metabolic/allosteric arm (e.g. acetyl-CoA on pyruvate carboxylase ); slow = hormonal arm (transcriptional + phosphorylation)

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