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Metabolic Integration — Fed, Fasting, and Starvation

Tier 1 · #1 of 33 · highest yield · topic 4.9 — every high-yield fact from the book chapter, exam-ready.

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  1. Front
    What single ratio is the master switch coordinating all of metabolism between storage and mobilization ?
    Back
    The insulin-to-glucagon (I/G) ratio
  2. Front
    A HIGH insulin/glucagon ratio puts the body in which metabolic mode?
    Back
    Fed mode ( store energy , build macromolecules )
  3. Front
    Glucagon and epinephrine raise cAMP , which activates which kinase?
    Back
    Protein kinase A (PKA)
  4. Front
    General phosphorylation rule: CATABOLIC enzymes are active in which covalent state?
    Back
    Phosphorylated (active)
  5. Front
    A LOW insulin/glucagon ratio puts the body in which metabolic mode?
    Back
    Mobilization mode ( release stored fuels , protect blood glucose )
  6. Front
    General phosphorylation rule: ANABOLIC enzymes are active in which covalent state?
    Back
    Dephosphorylated (active)
  7. Front
    Insulin reverses PKA-driven phosphorylation by activating which enzyme?
    Back
    Protein phosphatase-1 (via the PI3K/PKB cascade)
  8. Front
    Which cellular energy sensor is allosterically activated by rising AMP (not by hormones)?
    Back
    AMP-activated protein kinase (AMPK)
  9. Front
    AMPK phosphorylates and inhibits which enzyme, thereby lowering malonyl-CoA and activating beta-oxidation?
    Back
    Acetyl-CoA carboxylase (ACC)
  10. Front
    Metformin , the most prescribed Type 2 diabetes drug, works by activating which kinase?
    Back
    AMPK ( suppresses hepatic gluconeogenesis , promotes muscle glucose uptake )
  11. Front
    Above roughly what blood glucose threshold (mg/dL) do pancreatic beta cells begin releasing insulin ?
    Back
    ~80 mg/dL
  12. Front
    Which glucose transporter and which kinase let beta cells sense glucose in proportion to its blood concentration?
    Back
    GLUT-2 and glucokinase (both low-affinity)
  13. Front
    In the FED liver , PFK-2 is in which covalent form?
    Back
    Dephosphorylated (active)
  14. Front
    What molecule, made by PFK-2 , is the most potent allosteric ACTIVATOR of PFK-1 ?
    Back
    Fructose-2,6-bisphosphate (F-2,6-BP)
  15. Front
    Besides activating PFK-1 , F-2,6-BP INHIBITS which gluconeogenic enzyme?
    Back
    Fructose-1,6-bisphosphatase (FBPase-1)
  16. Front
    In the fed liver , acetyl-CoA is exported from the mitochondrion to the cytosol as which molecule for fatty acid synthesis?
    Back
    Citrate (via the citrate shuttle)
  17. Front
    What is the first committed step of fatty acid synthesis (carboxylation of acetyl-CoA to malonyl-CoA ) catalyzed by?
    Back
    Acetyl-CoA carboxylase-1 (ACC-1)
  18. Front
    Which two cofactors does ACC require to make malonyl-CoA ?
    Back
    Biotin and ATP
  19. Front
    Fatty acid synthase uses which reducing cofactor to elongate the fatty acid chain?
    Back
    NADPH (from the pentose phosphate pathway and malic enzyme)
  20. Front
    What is the final fatty acid product of fatty acid synthase ?
    Back
    Palmitate (16:0)
  21. Front
    Newly synthesized hepatic triacylglycerol is packaged into which lipoprotein for export to peripheral tissues ?
    Back
    VLDL
  22. Front
    In muscle and adipose tissue , insulin recruits which glucose transporter to the cell surface?
    Back
    GLUT-4
  23. Front
    Besides insulin , what else can recruit GLUT-4 to the membrane?
    Back
    AMPK / exercise
  24. Front
    In adipose tissue , glucose is metabolized to DHAP , which is reduced to what TAG-backbone molecule?
    Back
    Glycerol-3-phosphate
  25. Front
    Adipose tissue cannot phosphorylate free glycerol because it lacks which enzyme?
    Back
    Glycerol kinase
  26. Front
    Insulin stimulates which capillary-endothelium enzyme that hydrolyzes TAG in VLDL and chylomicrons ?
    Back
    Lipoprotein lipase (LPL)
  27. Front
    Which glucose transporters give the brain constitutive, insulin-independent glucose access?
    Back
    GLUT-1 and GLUT-3
  28. Front
    Cloze: Several hours after a meal, insulin falls and glucagon rises, so the I/G ratio ____ and the priority becomes maintaining blood glucose.
    Back
    falls
  29. Front
    What is the FIRST source the liver uses to defend blood glucose in early fasting?
    Back
    Hepatic glycogenolysis (glycogen breakdown)
  30. Front
    Liver glycogen maintains euglycemia for approximately how long before it is exhausted?
    Back
    About 12–18 hours
  31. Front
    Which enzyme, present only in liver and kidney , hydrolyzes glucose-6-phosphate to free glucose for export?
    Back
    Glucose-6-phosphatase
  32. Front
    Why can muscle glycogen NOT raise blood glucose?
    Back
    Muscle lacks glucose-6-phosphatase , so its glucose-6-phosphate cannot become free glucose and stays in the cell
  33. Front
    Lactate exported from muscle becomes a gluconeogenic substrate in the liver via which named cycle?
    Back
    The Cori cycle
  34. Front
    In fasting adipose tissue , which lipase is activated by PKA to release free fatty acids?
    Back
    Hormone-sensitive lipase (HSL)
  35. Front
    PKA phosphorylates which lipid-droplet coat protein to give lipase access to the TAG ?
    Back
    Perilipin
  36. Front
    How do free fatty acids travel in the blood?
    Back
    Bound to serum albumin
  37. Front
    Fatty acyl-CoA enters the mitochondrial matrix for beta-oxidation via which shuttle?
    Back
    The carnitine shuttle ( CPT-1 / CPT-2 )
  38. Front
    A high NADH / NAD+ ratio from beta-oxidation inhibits which enzyme, sparing oxaloacetate for gluconeogenesis?
    Back
    Pyruvate dehydrogenase
  39. Front
    Which gluconeogenic substrate enters the pathway at DHAP , bypassing pyruvate carboxylase ?
    Back
    Glycerol
  40. Front
    Which gluconeogenic substrate comes from transamination of pyruvate in muscle (the glucose-alanine cycle)?
    Back
    Alanine
  41. Front
    What is the key regulated enzyme of gluconeogenesis, inhibited by AMP and F-2,6-BP ?
    Back
    Fructose-1,6-bisphosphatase (FBPase-1)
  42. Front
    Pyruvate carboxylase ( pyruvate → oxaloacetate ) is allosterically ACTIVATED by which molecule?
    Back
    Acetyl-CoA
  43. Front
    Which cofactor does pyruvate carboxylase require?
    Back
    Biotin
  44. Front
    In the LIVER , PKA phosphorylation of PFK-2/FBPase-2 activates which domain?
    Back
    The FBPase-2 domain (lowering F-2,6-BP → gluconeogenesis ON )
  45. Front
    In MUSCLE/heart , PKA ( epinephrine ) phosphorylation of PFK-2/FBPase-2 activates which domain?
    Back
    The PFK-2 domain (raising F-2,6-BP → glycolysis ON )
  46. Front
    Why does epinephrine drive muscle PFK-2 to RAISE F-2,6-BP (opposite of liver)?
    Back
    Muscle does no gluconeogenesis; during stress/exercise it should burn glucose maximally for burst energy
  47. Front
    In starvation, excess hepatic acetyl-CoA is diverted to ketogenesis because the Krebs cycle lacks which intermediate?
    Back
    Oxaloacetate (diverted into gluconeogenesis)
  48. Front
    Two acetyl-CoA condense via thiolase to form which intermediate at the start of ketogenesis?
    Back
    Acetoacetyl-CoA
  49. Front
    Which enzyme adds a third acetyl-CoA to acetoacetyl-CoA to form HMG-CoA in ketogenesis?
    Back
    HMG-CoA synthase
  50. Front
    Which enzyme cleaves HMG-CoA to release acetoacetate ?
    Back
    HMG-CoA lyase
  51. Front
    Spontaneous decarboxylation of acetoacetate yields which exhaled ketone (the fruity/apple smell)?
    Back
    Acetone
  52. Front
    Which ketone body is the most abundant in circulation?
    Back
    Beta-hydroxybutyrate (beta-OHB)
  53. Front
    The liver makes ketone bodies but cannot use them because it lacks which enzyme?
    Back
    Succinyl-CoA:acetoacetate CoA transferase (SCOT / thiophorase)
  54. Front
    Why can red blood cells NEVER use ketone bodies or fatty acids?
    Back
    They lack mitochondria
  55. Front
    Approximately how many ATP are yielded by oxidation of one acetoacetate molecule in peripheral tissue ?
    Back
    ~19 ATP
  56. Front
    In prolonged starvation, up to what fraction of the brain 's energy can come from ketone bodies?
    Back
    Up to ~70%
  57. Front
    State the starvation survival logic in one chain: ketones spare ____, which spares ____.
    Back
    Ketones spare glucose , which spares muscle protein
  58. Front
    Malonyl-CoA is the off-switch for beta-oxidation because it inhibits which transporter enzyme?
    Back
    CPT-1 (carnitine palmitoyltransferase-1)
  59. Front
    In fasting, why does malonyl-CoA fall (releasing CPT-1 and enabling beta-oxidation)?
    Back
    ACC is phosphorylated and inactive , so less malonyl-CoA is made
  60. Front
    Which fuel does the BRAIN use exclusively in both the fed and early-fasting states?
    Back
    Glucose
  61. Front
    Which fuel do red blood cells depend on for their entire lifetime, in every metabolic state?
    Back
    Glucose (anaerobic glycolysis to lactate)
  62. Front
    At rest in the FED state, what is the heart 's PRIMARY fuel?
    Back
    Fatty acids (~50%)
  63. Front
    Why is gluconeogenesis never fully abandoned even in extreme starvation?
    Back
    The brain 's glucose requirement never drops to zero , and RBCs always need glucose
  64. Front
    In adipose tissue during prolonged starvation, which lipolysis product is exported as a gluconeogenic substrate?
    Back
    Glycerol
  65. Front
    In uncontrolled Type 1 diabetes , why are muscle and adipose locked out of glucose?
    Back
    Without insulin , GLUT-4 cannot translocate to the cell surface
  66. Front
    In uncontrolled Type 1 diabetes , why does blood glucose climb so high?
    Back
    Peripheral tissues cannot take glucose up (GLUT-4 not on the membrane); gluconeogenesis adds to it
  67. Front
    Name the triad of diabetic ketoacidosis (DKA) .
    Back
    Hyperglycemia, ketosis, and acidosis
  68. Front
    Why is DKA acidotic?
    Back
    Acetoacetate and beta-hydroxybutyrate are acids
  69. Front
    Glycogen phosphorylase is active in which covalent form?
    Back
    Phosphorylated (catabolic enzyme)
  70. Front
    Glycogen synthase is active in which covalent form?
    Back
    Dephosphorylated (anabolic enzyme)
  71. Front
    Liver pyruvate kinase (L) is active in which covalent form?
    Back
    Dephosphorylated ( inactive when phosphorylated in fasting )
  72. Front
    Pyruvate dehydrogenase is active in which covalent form (and what inhibits it in fasting)?
    Back
    Dephosphorylated ; inhibited by NADH and acetyl-CoA
  73. Front
    Hormone-sensitive lipase (HSL) is active in which covalent form?
    Back
    Phosphorylated (catabolic enzyme)
  74. Front
    HMG-CoA reductase (cholesterol synthesis) is active in which covalent form, and which kinase inactivates it?
    Back
    Dephosphorylated (active); inactivated by phosphorylation via AMPK
  75. Front
    Which gluconeogenesis enzyme is regulated allosterically (by acetyl-CoA ) rather than by phosphorylation?
    Back
    Pyruvate carboxylase
  76. Front
    A biotin deficiency blocks gluconeogenesis from lactate and alanine but NOT from which substrate?
    Back
    Glycerol (enters at DHAP , bypassing pyruvate carboxylase )
  77. Front
    In peripheral (extrahepatic) tissue , which enzyme reactivates acetoacetate to acetoacetyl-CoA so it can be used as fuel?
    Back
    SCOT (succinyl-CoA:acetoacetate CoA transferase)
  78. Front
    After SCOT reactivates acetoacetate to acetoacetyl-CoA in peripheral tissue , which enzyme splits it into 2 acetyl-CoA for the Krebs cycle?
    Back
    Thiolase
  79. Front
    How do ketone bodies ( acetoacetate and beta-OHB ) travel in plasma?
    Back
    Freely dissolved — water-soluble, WITHOUT a carrier protein
  80. Front
    Cloze: Free fatty acids require ____ to travel in blood, whereas ketone bodies need no carrier at all.
    Back
    serum albumin
  81. Front
    Which enzyme reduces acetoacetate to beta-hydroxybutyrate (beta-OHB) ?
    Back
    3-hydroxybutyrate dehydrogenase
  82. Front
    In adipose lipolysis, which enzyme acts FIRST, converting TAG to diacylglycerol before phospho-HSL completes hydrolysis?
    Back
    ATGL (adipose triglyceride lipase)
  83. Front
    Put the adipose lipolysis cascade in order: TAG → ___ → completed hydrolysis. Which enzyme catalyzes each step?
    Back
    ATGL converts TAG → diacylglycerol ; then phospho-HSL completes the hydrolysis
  84. Front
    In uncontrolled Type 1 diabetes , what drives the muscle wasting?
    Back
    Glucagon-driven protein catabolism supplying amino acids for futile gluconeogenesis
  85. Front
    In DKA , why do BOTH glucose and ketones appear in the urine (glucosuria and ketonuria)?
    Back
    The renal threshold for each is exceeded
  86. Front
    Which enzyme is THE rate-limiting (committed) step of glycolysis?
    Back
    PFK-1 (phosphofructokinase-1)
  87. Front
    In the cytosol , which enzyme cleaves the exported citrate to regenerate acetyl-CoA for fatty acid synthesis?
    Back
    Citrate lyase (ATP-citrate lyase)
  88. Front
    Cloze: In peripheral tissue , oxidation of one acetoacetate yields about ____ ATP after SCOT and thiolase regenerate 2 acetyl-CoA .
    Back
    19
  89. Front
    Why can the LIVER export ketone bodies but never oxidize them itself?
    Back
    It lacks SCOT , so it cannot reactivate acetoacetate to acetoacetyl-CoA
  90. Front
    Besides T1DM muscle wasting and the fruity breath, name the two urinary findings of DKA .
    Back
    Glucosuria and ketonuria
  91. Front
    In prolonged starvation, the brain derives ~70% of its energy from ketones and roughly what fraction from glucose ?
    Back
    About 30% from glucose
  92. Front
    In prolonged starvation, what is the heart 's approximate fuel mix (FA vs ketones)?
    Back
    FA ~45% and ketone bodies ~40% (plus ~5% lactate, ~5% glucose)
  93. Front
    By what transporters do ketone bodies ( acetoacetate , beta-OHB ) cross the blood-brain barrier into neurons ?
    Back
    Monocarboxylate transporters
  94. Front
    In prolonged starvation, skeletal muscle begins protein catabolism and releases which glucogenic amino acid for hepatic gluconeogenesis?
    Back
    Alanine
  95. Front
    Besides dephosphorylation (insulin), which molecule allosterically ACTIVATES acetyl-CoA carboxylase (ACC) in the fed liver ?
    Back
    Citrate

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