BMS700: Metabolism and Energy Balance

1. Energy balance components — which contribute to Total Daily Energy Expenditure (TDEE)?
   Basal/resting metabolic rate (BMR/RMR)
   Thermic effect of food (TEF)
   Non-exercise activity thermogenesis (NEAT) + exercise activity
   Adaptive thermogenesis (cold, overfeeding)

A, B, C, D
Explanation: TDEE ≈ RMR (60–75%) + Activity (15–30%but highly variable) + TEF (~10% ) + adaptive components.

2. Basal vs resting metabolic rate — correct statements:
   BMR measured after 12h fast, thermoneutral, supine
   RMR is typically 5–10% higher than BMR
   Thyroid hormones, lean mass ↑ BMR
   BMR decreases acutely with a single high-carb meal

A, B, C
Explanation: BMR is tightly standardized; RMR is less strict. A single meal does not decrease BMR; it adds TEF.

3. Thermic effect of food (TEF) — which are accurate?
   Protein has the highest TEF (~20–30%)
   Carbohydrate TEF ~5–10%; Fat TEF ~0–3% TEF is identical regardless of insulin resistance

A, B, C
Explanation: Protein is costly to process; TEF varies with insulin sensitivity, meal composition, and size.

4. Respiratory Quotient (RQ) — choose the correct pairings:
   Pure carbohydrate oxidation → RQ ≈ 1.0
   Pure fat oxidation → RQ ≈ 0.70
   Mixed diet RQ ≈ 0.8
   Ketone oxidation RQ ≈ 1.1

A, B, C
Explanation: RQ >1 occurs during net lipogenesis from carbohydrate; ketone oxidation is ~0.7–0.8.

5. Fed-state (postprandial) liver metabolism — true:
   ↑ Glycolysis and glycogen synthesis
   ↑ De novo lipogenesis when glycogen stores adequate
   ↑ VLDL export of TAG
   ↑ Hepatic gluconeogenesis

A, B, C
Explanation: Insulin suppresses hepatic gluconeogenesis in the fed state.

6. Postabsorptive/fasted liver (overnight) — correct:
   ↑ Glycogenolysis (early fasting)
   ↑ Gluconeogenesis (lactate, glycerol, alanine)
   ↑ Ketogenesis within hours of fasting
   ↑ De novo lipogenesis

A, B, C
Explanation: Lipogenesis is off; ketogenesis ramps up as hepatic acetyl-CoA rises.

7. Prolonged starvation (>3–5 days) — metabolic shifts:
   Brain increases ketone usage (β-hydroxybutyrate, acetoacetate)
   Muscle protein breakdown initially high, then decreases
   Glucose requirement of brain declines
   Obligate glucose users still include RBCs

A, B, C, D
Explanation: Ketones spare protein; RBCs (no mitochondria) must use glucose.

8. Glycolysis regulation — which increase flux?
   ↑ PFK-1 activity via fructose-2,6-bisphosphate
   ↑ Hexokinase/glucokinase activity (availability of substrate)
   High ATP and citrate levels
   AMP and ADP elevations

A, B, D
Explanation: ATP and citrate inhibit PFK-1; AMP/ADP stimulate.

9. Pyruvate fates — accurate mappings:
   → Acetyl-CoA via PDH (aerobic)
   → Lactate via LDH (anaerobic/high glycolytic flux)
   → Oxaloacetate via pyruvate carboxylase (gluconeogenesis)
   → Citrate directly in cytosol without mitochondria

A, B, C
Explanation: Citrate forms in mitochondria from acetyl-CoA + OAA then can be exported.

10. Pyruvate dehydrogenase (PDH) complex — regulation:
    Activated by Ca²⁺ (muscle) and dephosphorylation (insulin)
    Inhibited by acetyl-CoA and NADH
    Thiamine (TPP) is a required cofactor
    Upregulated by chronic fasting and glucagon

A, B, C
Explanation: Fasting/glucagon favor PDH kinase activity → PDH inhibition.

11. TCA cycle control points — correct:
    Citrate synthase inhibited by citrate
    Isocitrate dehydrogenase activated by ADP/Ca²⁺
    α-Ketoglutarate dehydrogenase inhibited by NADH
    Cycle runs independently of O₂ availability

A, B, C
Explanation: TCA requires O₂ indirectly via ETC to reoxidize NADH/FADH₂.

12. Electron transport chain (ETC) — correct pairings:
    Complex I → NADH dehydrogenase (pumps H⁺)
    Complex II → succinate dehydrogenase (no H⁺ pumping)
    Complex III/IV pump protons; O₂ reduced at Complex IV
    ATP synthase uses proton motive force to form ATP

A, B, C, D
Explanation: Complex II feeds electrons from FADH₂ without proton pumping.

13. Oxidative phosphorylation uncoupling — true:
    UCP1 in brown adipose mediates nonshivering thermogenesis
    Chemical uncouplers ↑ O₂ consumption, ↓ ATP yield
    Uncoupling collapses ΔpH and ΔΨ, generating heat
    Oligomycin is an uncoupler

A, B, C
Explanation: Oligomycin inhibits ATP synthase (not an uncoupler).

14. Glycogen metabolism — enzymes & regulation:
    Glycogen synthase activated by insulin-stimulated dephosphorylation
    Glycogen phosphorylase activated by phosphorylation (epinephrine/glucagon)
    Muscle lacks glucose-6-phosphatase; cannot release free glucose
    Liver glycogen supports contracting muscle directly via blood

A, B, C
Explanation: Liver maintains blood glucose; muscle glycogen is for local use only.

15. Gluconeogenesis — substrates and control:
    Major substrates: lactate, glycerol, alanine
    PEPCK, FBPase-1, G6Pase are key enzymes
    Insulin upregulates PEPCK expression
    Acetyl-CoA activates pyruvate carboxylase

A, B, D
Explanation: Insulin downregulates gluconeogenic genes (PEPCK).

16. Cori cycle & glucose-alanine cycle — correct:
    Cori: muscle lactate → liver → glucose
    Alanine cycle: muscle transaminates pyruvate → alanine → liver → glucose
    Both shift nitrogen and gluconeogenic burden to liver
    Both reduce total ATP cost of exercise

A, B, C
Explanation: These cycles cost hepatic ATP to sustain muscle work.

17. Fatty acid β-oxidation — requirements:
    Carnitine shuttle for long-chain acyl-CoA import (via CPT-I/CPT-II)
    Malonyl-CoA inhibits CPT-I (anti-futile cycling)
    Generates FADH₂, NADH, and acetyl-CoA each cycle
    Occurs in cytosol predominantly

A, B, C
Explanation: β-Oxidation is mitochondrial (very-long-chain FA start in peroxisomes).

18. Ketogenesis — conditions & products:
    Produced in liver mitochondria from acetyl-CoA (HSL-driven lipolysis upstream)
    Main ketones: acetoacetate, β-hydroxybutyrate, acetone
    Stimulated by low insulin/high glucagon states, fasting, uncontrolled T1D
    Peripheral utilization requires hepatic succinyl-CoA transferase

A, B, C
Explanation: Liver lacks succinyl-CoA:acetoacetate CoA transferase (SCOT); extrahepatic tissues use ketones.

19. De novo lipogenesis (DNL) — specifics:
    Occurs in cytosol (liver, adipose); ACC makes malonyl-CoA
    Fatty acid synthase elongates to palmitate (16:0)
    Citrate shuttle provides cytosolic acetyl-CoA and NADPH (PPP also)
    Glucagon acutely activates ACC

A, B, C
Explanation: ACC is activated by insulin/citrate; inhibited by glucagon/AMPK phosphorylation.

20. Cholesterol metabolism & lipoproteins:
    HMG-CoA reductase is rate-limiting; inhibited by statins
    LDL delivers cholesterol to tissues via LDLR
    HDL mediates reverse cholesterol transport via LCAT/CETP/SR-B1
    Chylomicrons deliver hepatic TAG to muscle

A, B, C
Explanation: Chylomicrons deliver dietary TAG from intestine via LPL to adipose/muscle; VLDL delivers hepatic TAG.

21. Key lipoprotein enzymes/proteins — match correctly:
    LPL: hydrolyzes TAG in chylomicrons/VLDL at capillary endothelium
    HL (hepatic lipase): remodels IDL/HDL
    LCAT: esterifies cholesterol on HDL surface
    CETP: transfers CE ↔ TAG between HDL and VLDL/LDL

A, B, C, D
Explanation: These coordinate TAG removal and cholesterol exchange.

22. Hormone-sensitive lipase (HSL) & adipose lipolysis:
    Activated by epinephrine/β-adrenergic → ↑ cAMP/PKA
    Insulin inhibits lipolysis via phosphodiesterase (↓ cAMP)
    Perilipin phosphorylation facilitates lipid droplet access
    HSL deficiency increases fasting ketogenesis

A, B, C
Explanation: Impaired lipolysis lowers FFA → reduces ketogenesis.

23. Insulin signaling — downstream metabolic effects:
    Activates AKT → ↑ GLUT4 translocation (muscle/adipose)
    Activates phosphatases (PP1) → ↑ glycogen synthase, ↓ phosphorylase
    Activates ACC (via dephosphorylation) → ↑ DNL
    Activates PKA → ↑ glycogen phosphorylase

A, B, C
Explanation: PKA is glucagon/epinephrine pathway; insulin opposes it.

24. Glucagon & epinephrine — acute hepatic effects:
    ↑ Glycogenolysis (phosphorylase a)
    ↑ Gluconeogenesis (PEPCK expression with chronic glucagon)
    ↑ Lipolysis in adipose (epinephrine) → ↑ FFA to liver
    ↑ Glycogen synthase activity

A, B, C
Explanation: Glucagon/epi inhibit glycogen synthase via phosphorylation.

25. AMPK vs mTOR — catabolic/anabolic switches:
    AMPK activated by ↑ AMP/ADP, exercise, metformin → ↑ catabolism, ↓ anabolism
    AMPK inhibits ACC and mTORC1
    mTORC1 activated by insulin/AA (Leu) → ↑ protein/lipid synthesis
    mTORC1 activation increases autophagy

A, B, C
Explanation: mTORC1 inhibits autophagy; AMPK promotes it.

26. Thyroid hormones & metabolism:
    T3 increases basal metabolic rate via Na⁺/K⁺-ATPase, mitochondrial biogenesis
    T3 increases lipolysis and glycogenolysis
    Hypothyroidism → weight gain, cold intolerance, ↓ BMR
    Hyperthyroidism → ↓ β-adrenergic sensitivity

A, B, C
Explanation: Hyperthyroidism increases β-adrenergic sensitivity.

27. Adipokines & appetite signals:
    Leptin (from adipose) → anorexigenic (↑ POMC/CART, ↓ NPY/AgRP)
    Ghrelin (stomach) rises pre-meal → orexigenic
    Adiponectin improves insulin sensitivity, ↑ FA oxidation (AMPK)
    Resistin acutely lowers hepatic glucose output

A, B, C
Explanation: Resistin is associated with insulin resistance, not lower HGP.

28. Metabolic syndrome — diagnostic features (typical set):
    Central obesity (waist), ↑ TG, ↓ HDL
    Hypertension, ↑ fasting glucose
    Pro-inflammatory/pro-thrombotic state
    Must have overt T2D diagnosis to qualify

A, B, C
Explanation: Metabolic syndrome is a pre-diabetes risk cluster; T2D not required.

29. Insulin resistance — cellular mechanisms:
    Ectopic lipid (DAG/ceramides) → PKC activation → impaired IRS-1
    Inflammation (TNF-α, JNK) → serine phosphorylation of IRS
    Mitochondrial dysfunction/ROS can worsen signaling
    Increased GLUT4 transcription rescues insulin resistance instantly

A, B, C
Explanation: GLUT4 expression helps, but resistance is multifactorial and not “instant” to reverse.

30. Glycemic index/load — correct statements:
    GI reflects postprandial glucose vs reference (glucose/white bread)
    GL = GI × carb grams per serving / 100
    High fiber/fat/protein lower GI
    GI equals “healthfulness” of a food in all contexts

A, B, C
Explanation: GI is one metric; nutrient density and context matter.

31. Protein turnover & nitrogen balance:
    Positive nitrogen balance: growth, pregnancy, recovery
    Negative nitrogen balance: illness, trauma, inadequate protein
    Essential amino acids must be supplied by diet
    Transamination requires PLP (vitamin B6)

A, B, C, D
Explanation: All correct.

32. Urea cycle — nitrogen disposal:
    Key substrate: NH₃ and aspartate (two nitrogens)
    Rate-limiting CPS-I requires N-acetylglutamate (NAG)
    Occurs mainly in liver (mitochondrial + cytosolic steps)
    Defect causes respiratory alkalosis from H⁺ retention

A, B, C
Explanation: Hyperammonemia often leads to respiratory alkalosis via central stimulation, but “from H⁺ retention” is incorrect phrasing.

33. B-vitamin coenzymes — match roles:
    Thiamine (B1/TPP): PDH, α-KG DH, transketolase
    Riboflavin (B2/FAD): ETC (Complex II), acyl-CoA DH
    Niacin (B3/NAD⁺/NADP⁺): redox, dehydrogenases, PPP
    Biotin (B7): carboxylation (ACC, pyruvate carboxylase, propionyl-CoA carboxylase)

A, B, C, D
Explanation: Classic coenzyme roles.

34. Fat-soluble vitamins — key metabolic functions:
    Vit A (retinoic acid): gene regulation; retinal in vision
    Vit D (calcitriol): Ca²⁺/PO₄³⁻ homeostasis; gene transcription
    Vit E: lipid antioxidant
    Vit K: γ-carboxylation of clotting factors; ETC cofactor

A, B, C
Explanation: Vit K is for γ-carboxylation (II, VII, IX, X, proteins C/S), not an ETC cofactor.

35. Alcohol metabolism — accurate sequence & effects:
    ADH: ethanol → acetaldehyde (NADH generated)
    ALDH: acetaldehyde → acetate (NADH generated)
    High NADH:NAD⁺ ratio → ↑ lactate, ↓ gluconeogenesis, ↑ fatty liver
    MEOS (CYP2E1) induced with chronic intake

A, B, C, D
Explanation: Excess NADH drives steatosis and hypoglycemia risk.

36. Fructose metabolism (liver) — implications:
    Fructokinase → F1P (bypasses PFK-1)
    Aldolase B → DHAP + glyceraldehyde → lipogenesis substrate
    High fructose may ↑ DNL and VLDL
    Fructose acutely raises insulin strongly in peripheral tissues

A, B, C
Explanation: Fructose has minimal acute insulin response (no GLUT4 stimulation directly).

37. Galactose metabolism — Leloir pathway:
    Galactokinase → Gal-1-P
    GALT: Gal-1-P + UDP-glucose → UDP-galactose + Glc-1-P
    Defects (classic galactosemia) → cataracts, liver failure
    Pathway occurs only in muscle

A, B, C
Explanation: Occurs in many tissues, notably liver.

38. Pentose phosphate pathway (PPP) — outcomes:
    Oxidative branch: NADPH + ribulose-5-P
    Non-oxidative: interconverts sugars (transketolase/transaldolase)
    NADPH: reductive biosynthesis, glutathione reduction
    Pathway is mitochondrial exclusively

A, B, C
Explanation: PPP is cytosolic.

39. Reactive oxygen species (ROS) & antioxidants:
    Mitochondria are major ROS source (Complex I/III leak)
    Glutathione peroxidase uses GSH; glutathione reductase uses NADPH
    SOD converts O₂•⁻ → H₂O₂; catalase/GPx clear H₂O₂
    NADPH depletion impairs antioxidant defense

A, B, C, D
Explanation: All correct.

40. Exercise metabolism — rapid ATP sources:
    Phosphocreatine system (~10 s)
    Anaerobic glycolysis (lactate) for short high-intensity
    Aerobic oxidation dominates after ~2 min
    Fat oxidation peaks in first 10 s

A, B, C
Explanation: Fat oxidation ramps with time; not immediate.

41. Endurance vs sprint metabolism — fuel use:
    Sprint: ATP-PCr + glycolysis; high lactate; low fat usage
    Endurance: ↑ fat oxidation, glycogen sparing
    Cori cycle activity increases with intense efforts
    Gluconeogenesis shuts off during endurance

A, B, C
Explanation: Endurance maintains some gluconeogenesis to support blood glucose.

42. Brown vs white adipose tissue — thermogenesis:
    Brown adipose: multilocular lipid, abundant mitochondria, UCP1
    Cold exposure ↑ sympathetic drive → UCP1 activation
    White adipose specialized for storage; endocrine organ
    UCP1 increases ATP yield per O₂

A, B, C
Explanation: UCP1 uncouples → heat, not more ATP.

43. Electrolytes & performance metabolism:
    Na⁺ critical for extracellular volume & glucose co-transport
    K⁺ influences membrane excitability; loss → muscle weakness
    Mg²⁺ cofactor for ATP-dependent kinases
    All lost equally in sweat at identical rates

A, B, C
Explanation: Sweat composition varies; Na⁺ loss predominates vs others.

44. Water balance & energy metabolism:
    Mild dehydration impairs aerobic performance and thermoregulation
    High protein intake increases urea production and water need
    Glycogen is stored with water (~3 g water per g glycogen)
    Dehydration lowers RMR by 30% acutely

A, B, C
Explanation: Dehydration reduces performance; acute RMR drop by 30% is incorrect.

45. Micronutrients critical for energy pathways — identify true pairs:
    Thiamine deficiency → impaired PDH/TCA (beriberi, Wernicke)
    Niacin deficiency → pellagra (dermatitis, diarrhea, dementia)
    Riboflavin deficiency → stomatitis, cheilosis; ETC impairment
    Vitamin C is an obligatory cofactor for ATP synthase

A, B, C
Explanation: Vit C is not part of ATP synthase; it aids collagen synthesis/antioxidant defense

46. Fed vs fasting metabolic hormones — correct pairings:
A. Insulin: promotes anabolic processes (glycogen, fat, protein synthesis)
B. Glucagon: promotes catabolic processes (glycogenolysis, gluconeogenesis, lipolysis)
C. Epinephrine: mimics glucagon in liver and adipose
D. Insulin increases CPT-I activity to stimulate β-oxidation

A, B, C
Explanation: Insulin inhibits CPT-I via ↑ malonyl-CoA; fasting hormones activate it.

47. Tissue-specific glucose transporters — correct matches:
A. GLUT1 – basal uptake (RBCs, brain, placenta)
B. GLUT2 – liver, pancreas (bidirectional; high Km)
C. GLUT3 – neurons (low Km, high affinity)
D. GLUT4 – skeletal muscle, adipose (insulin-regulated)

A, B, C, D
Explanation: GLUT1/3 ensure constant brain/RBC supply; GLUT4 responsive to insulin.

48. Glucose homeostasis in fasting — key points:
A. Glycogenolysis maintains glucose for first 12–18 hrs
B. Gluconeogenesis dominates after ~24 hrs
C. Brain adapts to ketones after ~3 days
D. RBCs switch to fatty acids for energy

A, B, C
Explanation: RBCs lack mitochondria → always use glycolysis → lactate.

49. Muscle fiber types and energy metabolism:
A. Type I (slow-twitch): high mitochondria, oxidative, fatigue-resistant
B. Type IIb (fast glycolytic): low mitochondria, high glycogen, fatigues fast
C. Type IIa (intermediate): oxidative + glycolytic adaptable
D. Type I fibers use mostly glycogen anaerobically

A, B, C
Explanation: Type I relies on aerobic oxidation of fats/glucose; not anaerobic.

50. Heart metabolism — substrate use:
A. Prefers fatty acids at rest (~60–70%)
B. Uses glucose and lactate during exercise
C. Ketones important in prolonged fasting
D. Cannot oxidize lactate

A, B, C
Explanation: The heart oxidizes lactate efficiently; highly aerobic.

51. Brain metabolism — characteristics:
A. Needs continuous glucose (≈120 g/day)
B. Uses ketones during starvation
C. Cannot oxidize fatty acids (BBB impermeable)
D. Glycogen stores supply energy for 12 hrs

A, B, C
Explanation: Brain has almost no glycogen; depends on blood-borne fuels.

52. Red blood cells – unique metabolism:
A. Lack mitochondria → only anaerobic glycolysis
B. Produce lactate → Cori cycle substrate
C. Pentose phosphate pathway provides NADPH for glutathione
D. Can synthesize fatty acids in cytosol

A, B, C
Explanation: RBCs cannot synthesize or oxidize fats.

53. Kidney metabolism – unique roles:
A. Renal cortex performs gluconeogenesis during fasting
B. Uses glutamine → NH₄⁺ for acid excretion
C. Produces glucose during acidosis
D. Cannot utilize lactate

A, B, C
Explanation: Lactate is a gluconeogenic substrate for kidney.

54. Adipose tissue metabolism:
A. Fed: insulin ↑ glucose uptake (GLUT4) → glycerol-3-P for TAG synthesis
B. Fasting: lipolysis via HSL → FFA + glycerol
C. Glycerol reused locally for TAG re-esterification
D. Adipose converts glycerol → glucose directly

A, B, C
Explanation: Adipose lacks glycerol kinase → cannot convert glycerol to glucose.

55. Liver–adipose metabolic cooperation:
A. Liver converts excess glucose → fatty acids → TAG → VLDL → adipose
B. Adipose releases FFA during fasting → liver ketogenesis
C. Glycerol from adipose used by liver for gluconeogenesis
D. Liver uses ketones for energy

A, B, C
Explanation: Liver exports, not consumes, ketones (lacks SCOT enzyme).

56. Muscle–liver cooperation:
A. Alanine/lactate from muscle → liver gluconeogenesis (Cori & alanine cycles)
B. Glucose from liver → muscle glycogen synthesis
C. During exercise, epinephrine activates glycogen phosphorylase via Ca²⁺ and cAMP
D. Muscle exports glucose-6-phosphate via G6Pase

A, B, C
Explanation: Muscle lacks G6Pase → keeps G6P for its own energy.

57. Hormonal control of fuel use (fed vs fasted):
A. Insulin → anabolic; Glucagon/Epi → catabolic
B. Cortisol → catabolic (proteolysis, gluconeogenesis)
C. GH → lipolytic, protein-sparing
D. Insulin activates AMPK to enhance catabolism

A, B, C
Explanation: Insulin suppresses AMPK; fasting hormones activate it.

58. Cortisol’s metabolic effects:
A. Increases gluconeogenesis and proteolysis
B. Decreases glucose uptake (insulin resistance)
C. Promotes lipolysis (chronic stress)
D. Stimulates glycogen synthesis for stress buffering

A, B, C, D
Explanation: Cortisol increases glucose output but also helps replenish glycogen stores in liver.

59. Growth hormone (GH):
A. Promotes protein synthesis and lipolysis
B. Decreases glucose uptake (anti-insulin)
C. Increases hepatic IGF-1 → growth effects
D. Stimulates glycogenolysis acutely

A, B, C
Explanation: GH spares glucose; short-term GH doesn’t acutely trigger glycogenolysis.

60. Catecholamine (Epi/Norepi) effects:
A. Activate glycogenolysis (liver, muscle)
B. Activate HSL in adipose
C. Stimulate gluconeogenesis via β-adrenergic receptors
D. Decrease cardiac output to conserve oxygen

A, B, C
Explanation: Epi increases cardiac output; not decreases.

61. AMPK (AMP-activated kinase) activation:
A. Triggered by energy stress (↑ AMP/ADP)
B. Increases glucose uptake in muscle (GLUT4)
C. Inhibits ACC and mTOR → ↓ lipogenesis & protein synthesis
D. Activated by insulin signaling

A, B, C
Explanation: AMPK is anti-anabolic, opposite insulin.

62. mTOR signaling:
A. Activated by insulin, amino acids (Leu), and growth factors
B. Stimulates protein synthesis and cell growth
C. Inhibited by rapamycin and AMPK
D. Required for autophagy activation

A, B, C
Explanation: mTOR suppresses autophagy; inhibition of mTOR reactivates it.

63. Thyroid hormone metabolism regulation:
A. T3 increases Na⁺/K⁺-ATPase activity → ↑ O₂ consumption
B. T3 induces mitochondrial biogenesis
C. T4 → T3 conversion via deiodinases (5’-D1/D2)
D. Cold exposure decreases T3 conversion

A, B, C
Explanation: Cold enhances conversion (thermogenesis).

64. Cushing syndrome vs Addison disease metabolic effects:
A. Cushing: hyperglycemia, protein loss, central obesity
B. Addison: hypoglycemia, weight loss, fatigue
C. Cushing: low cortisol
D. Addison: low cortisol and aldosterone

A, B, D
Explanation: Cushing = cortisol excess; Addison = deficiency.

65. Diabetes mellitus – type differences:
A. Type 1: autoimmune β-cell destruction, absolute insulin deficiency
B. Type 2: insulin resistance ± relative insulin deficiency
C. T1DM prone to DKA; T2DM to hyperosmolar coma
D. Both can cause chronic microvascular disease

A, B, C, D
Explanation: Both forms cause long-term complications via glycation.

66. Diabetic ketoacidosis (DKA) features:
A. High ketones (acetoacetate, β-hydroxybutyrate)
B. Anion-gap metabolic acidosis
C. Kussmaul breathing, fruity odor
D. Hypokalemia in plasma before therapy

A, B, C
Explanation: Serum K⁺ appears normal/high pre-treatment due to shift, total body K⁺ depleted.

67. Hyperosmolar hyperglycemic state (HHS):
A. Seen in type 2 DM
B. Very high glucose, minimal ketones
C. Severe dehydration, high plasma osmolarity
D. More common in young adults

A, B, C
Explanation: Elderly T2DM patients; enough insulin prevents ketosis.

68. Glycation (AGEs) effects:
A. Non-enzymatic glucose binding to proteins/lipids
B. Crosslinking in basement membranes → microangiopathy
C. HbA1c reflects long-term glycemia (8–12 weeks)
D. AGEs reduce oxidative stress

A, B, C
Explanation: AGEs increase ROS and inflammation.

69. Refeeding syndrome:
A. Rapid reintroduction of carbs → ↑ insulin → shifts K⁺, Mg²⁺, PO₄³⁻ into cells
B. Hypophosphatemia → ATP depletion, arrhythmias, failure
C. Thiamine deficiency risk → Wernicke encephalopathy
D. Occurs during prolonged fasting under steady feeding

A, B, C
Explanation: Occurs when restarting nutrition after prolonged catabolism.

70. Metabolic adaptation to starvation:
A. ↓ Resting energy expenditure
B. ↑ Efficiency of fuel use
C. Preferential fat oxidation
D. ↑ thermogenesis

A, B, C
Explanation: Thermogenesis decreases to conserve energy.

71. Thermoregulation and metabolism:
A. Shivering thermogenesis = muscle ATP hydrolysis → heat
B. Non-shivering thermogenesis = brown adipose via UCP1
C. Thyroid hormone enhances both
D. Sympathetic drive suppresses UCP1

A, B, C
Explanation: Sympathetic drive activates, not suppresses, UCP1.

72. Exercise training adaptations:
A. ↑ Mitochondrial density and oxidative enzymes
B. ↑ GLUT4 and insulin sensitivity
C. ↑ Capillary density
D. ↓ Fatty acid oxidation

A, B, C
Explanation: FA oxidation increases, not decreases.

73. VO₂ max and energy metabolism:
A. Measure of maximal aerobic capacity
B. Increases with endurance training
C. Correlates with cardiac output and O₂ delivery
D. Decreases with mitochondrial biogenesis

A, B, C
Explanation: Mitochondrial biogenesis raises VO₂ max.

74. High-intensity exercise metabolism:
A. Relies mainly on anaerobic glycolysis
B. Produces lactate; regenerates NAD⁺
C. Epinephrine ↑ glycogen breakdown
D. Fats supply majority of ATP

A, B, C
Explanation: Carbs dominate at high intensity; fat oxidation too slow.

75. Cori cycle function:
A. Transfers lactate from muscle → liver
B. Liver converts lactate → glucose (gluconeogenesis)
C. Costs hepatic ATP to support muscle
D. Conserves total energy

A, B, C
Explanation: Cycle supports muscle ATP but wastes total body ATP.

76. Protein catabolism during fasting:
A. Muscle proteolysis provides alanine and glutamine
B. Alanine → gluconeogenesis
C. Glutamine → renal ammonia excretion
D. Protein breakdown increases indefinitely with fasting

A, B, C
Explanation: Protein breakdown decreases as ketosis rises.

77. Fatty acid synthesis (cytosolic) – conditions:
A. High insulin, high citrate, high NADPH
B. ACC converts acetyl-CoA → malonyl-CoA (rate-limiting)
C. Palmitate product (C16:0)
D. Requires carnitine

A, B, C
Explanation: Carnitine is for β-oxidation, not synthesis.

78. PPARs and lipid metabolism:
A. PPAR-α: activated by fasting → ↑ β-oxidation (liver)
B. PPAR-γ: adipogenesis, insulin sensitivity (TZD drugs)
C. PPAR-δ: ↑ FA oxidation in muscle
D. PPAR-γ inhibits adipose expansion

A, B, C
Explanation: PPAR-γ promotes adipogenesis.

79. SREBP and cholesterol regulation:
A. SREBP-1c → fatty acid synthesis genes
B. SREBP-2 → cholesterol synthesis genes
C. Activated when ER cholesterol low
D. Inhibited by insulin

A, B, C
Explanation: Insulin activates SREBP-1c; not inhibits.

80. Malonyl-CoA – dual metabolic role:
A. Precursor for fatty acid synthesis
B. Inhibits CPT-I → prevents futile β-oxidation
C. Generated by ACC
D. Degraded by acetyl-CoA carboxylase

A, B, C
Explanation: Malonyl-CoA decarboxylase degrades it; not ACC.

81. Ketone utilization – tissues & enzymes:
A. Brain adapts after 2–3 days fasting
B. Skeletal & cardiac muscle use ketones readily
C. Liver cannot oxidize ketones (no SCOT)
D. RBCs use ketones efficiently

A, B, C
Explanation: RBCs lack mitochondria → no ketone oxidation.

82. Glycogen storage diseases (GSDs):
A. Von Gierke (Type I): G6Pase deficiency → hypoglycemia, lactic acidosis
B. McArdle (Type V): muscle phosphorylase deficiency → exercise intolerance
C. Pompe (Type II): lysosomal α-glucosidase defect → cardiomegaly
D. Hers (Type VI): liver phosphorylase kinase deficiency → hyperglycemia

A, B, C
Explanation: Hers → hypoglycemia, not hyper.

83. Lysosomal storage disorders (examples):
A. Gaucher – glucocerebrosidase deficiency
B. Tay-Sachs – hexosaminidase A deficiency
C. Niemann–Pick – sphingomyelinase deficiency
D. Fabry – β-galactosidase deficiency

A, B, C
Explanation: Fabry = α-galactosidase A deficiency.

84. Inborn errors of amino acid metabolism:
A. PKU – phenylalanine hydroxylase defect → phenylalanine ↑, tyrosine ↓
B. Alkaptonuria – homogentisate oxidase defect → dark urine
C. Maple syrup urine disease – branched-chain α-keto acid DH defect
D. PKU – requires vitamin B6 therapy

A, B, C
Explanation: BH₄ or diet control for PKU; B6 for homocystinuria, not PKU.

85. Urea cycle disorders:
A. CPS-I deficiency → hyperammonemia
B. Ornithine transcarbamylase (OTC) – X-linked
C. Citrullinemia (argininosuccinate synthase defect)
D. Hyperammonemia → metabolic alkalosis

A, B, C
Explanation: Hyperammonemia → respiratory alkalosis.

86. Oxidative stress in metabolism:
A. ROS from ETC (Complex I/III leak)
B. NADPH → regenerates reduced glutathione (GSH)
C. Vitamin E, C, carotenoids → antioxidants
D. Superoxide dismutase converts H₂O₂ → O₂

A, B, C
Explanation: SOD converts O₂•⁻ → H₂O₂; catalase handles H₂O₂.

87. Vitamin deficiencies with metabolic impact:
A. B1 – pyruvate & α-KG dehydrogenase impairment
B. B3 – NAD⁺ shortage → pellagra
C. B6 – transamination, heme synthesis defects
D. Biotin – oxidative phosphorylation defect

A, B, C
Explanation: Biotin = carboxylation, not ETC.

88. Electrolyte shifts during exercise:
A. K⁺ leaves contracting muscle → transient hyperkalemia
B. Na⁺ enters muscle during action potentials
C. Catecholamines promote Na⁺/K⁺ ATPase restoration
D. Mg²⁺ stabilizes ATP in muscle

A, B, C, D
Explanation: All are physiologic adaptations to contraction.

89. Metabolic rate modifiers:
A. Fever ↑ metabolic rate ~10–13% per °C
B. Hyperthyroidism ↑ RMR
C. Sleep ↓ metabolic rate
D. Aging ↑ metabolic rate

A, B, C
Explanation: Aging lowers RMR due to lean mass loss.

90. Adaptive thermogenesis & body weight regulation:
A. Cold → ↑ sympathetic → UCP1 heat
B. Overfeeding → ↑ futile cycling, thermogenesis
C. Leptin & thyroid axis modulate long-term adaptation
D. Weight loss increases leptin → higher RMR

A, B, C
Explanation: Weight loss ↓ leptin and RMR — promoting regain

91. Fed→Fasted transition (0–24h) — which shifts are correct?
A. Glycogenolysis rises within hours, peaking by ~8–12h
B. Hepatic gluconeogenesis becomes dominant by ~24h
C. Lipolysis decreases as insulin falls
D. Plasma FFA and glycerol rise as fasting proceeds

A, B, D
Explanation: As insulin drops, HSL activates → lipolysis ↑; FFAs/glycerol rise; gluconeogenesis takes over after glycogen wanes.

92. Prolonged fasting (≥3–5 days) — correct adaptations:
A. Brain increases ketone utilization to spare protein
B. Urea excretion falls compared with early fasting
C. RBCs begin oxidizing fatty acids
D. Thyroid axis downshifts to reduce RMR

A, B, D
Explanation: RBCs lack mitochondria → still glycolysis→lactate; protein sparing by ketones lowers urea output; RMR adapts downward.

93. Exercise + fasting overlap — fuel partitioning:
A. Moderate exercise in fasted state ↑ fat oxidation vs fed
B. High-intensity sprints still rely mainly on carbohydrates
C. Hepatic gluconeogenesis supports euglycemia during long fasted runs
D. Muscle exports glucose via G6Pase during exercise

A, B, C
Explanation: Muscle lacks G6Pase; glucose must come from liver (glycogenolysis/gluconeogenesis).

94. Obesity pathophysiology — mechanisms that maintain weight set point:
A. Leptin resistance blunts satiety signaling
B. Adaptive thermogenesis lowers RMR after weight loss
C. Reward circuitry (dopamine) biases toward hyperpalatable foods
D. FGF21 universally increases appetite for sugar

A, B, C
Explanation: FGF21 generally reduces sugar intake and promotes fat oxidation; leptin resistance + thermogenic adaptation sustain regain risk.

95. White→Beige (brite) adipocyte “browning” — drivers & outcomes:
A. Cold/β-adrenergic stimulation induces UCP1 expression
B. Irisin & BMP-7 promote beige differentiation
C. Beige fat increases ATP per O₂ consumed
D. Browning increases adaptive thermogenesis

A, B, D
Explanation: UCP1 uncouples → more heat, less ATP per O₂; thermogenesis rises.

96. Mitochondrial disorders — energy phenotypes:
A. ETC defects → exercise intolerance, lactic acidosis
B. Tissues with high ATP demand (muscle, CNS, heart) most affected
C. Heteroplasmy explains variable penetrance
D. Always improve with high-fat ketogenic diets

A, B, C
Explanation: Some benefit from tailored diets, but responses vary; not a universal fix.

97. Mitochondrial biogenesis signaling:
A. PGC-1α coactivator upregulates NRF1/TFAM → mtDNA replication
B. Endurance training, AMPK, and SIRT1 activate PGC-1α
C. Thyroid hormone suppresses mitochondrial number
D. Cold exposure can induce PGC-1α in brown/beige fat

A, B, D
Explanation: T3 generally promotes mitochondrial biogenesis and metabolic rate.

98. NAFLD/Metabolic dysfunction–associated steatotic liver (MASLD):
A. Insulin resistance ↑ adipose lipolysis → FFA flux to liver
B. Hepatic DNL from fructose/glucose contributes to TAG accumulation
C. VLDL export is unlimited, preventing steatosis
D. Progression to NASH involves oxidative stress & inflammation

A, B, D
Explanation: VLDL export is limited; excess FFA + DNL surpass export → steatosis → NASH via lipotoxicity/ROS.

99. Metabolic effects of sleep restriction & circadian misalignment:
A. ↓ Insulin sensitivity and glucose tolerance
B. ↑ Ghrelin, ↓ leptin → appetite up
C. ↑ Evening cortisol and sympathetic tone
D. Strong improvement in resting metabolic rate

A, B, C
Explanation: Sleep loss worsens glycemic control and appetite signaling; RMR doesn’t improve.

100. Micronutrient–metabolism links (critical cofactors):
A. Iodine → thyroid hormone synthesis
B. Selenium → deiodinases & glutathione peroxidase
C. Chromium → insulin signaling cofactor (controversial efficacy)
D. Copper deficiency → impaired ETC Complex IV

A, B, C, D
Explanation: All play roles; chromium’s clinical benefit is mixed, but it participates in insulin signaling complexes.