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Tell me everything important related to lipid metabolism, point wise, crisp, got an MCQ test tomorrow. Biochemistry

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I now have extensive data from Lippincott Biochemistry and Guyton. I have enough to compile a comprehensive MCQ-focused point-wise answer. Let me now compile everything:

🧬 LIPID METABOLISM β€” MCQ Master Notes (Biochemistry)

1. OVERVIEW & CLASSIFICATION

  • Lipids = fats, oils, phospholipids, sterols, waxes β€” hydrophobic/amphipathic
  • Major forms: Triacylglycerols (TAG/triglycerides), phospholipids, cholesterol, free fatty acids (FFA)
  • FFA in plasma are transported bound to albumin
  • 90% of plasma fatty acids are esterified (in TAG, cholesterol esters, phospholipids) within lipoprotein particles
  • Sites of lipid metabolism: Liver (central), adipose tissue, intestine, muscle

2. FATTY ACID STRUCTURE

  • Hydrophobic hydrocarbon chain + hydrophilic carboxyl group (pKa ~4.8) β†’ amphipathic
  • Saturated (no double bonds), monounsaturated, polyunsaturated
  • Cis configuration = common in humans; trans fats are unusual
  • Naming: Alpha (Ξ±) carbon = next to carboxyl; Beta (Ξ²) = next; Omega (Ο‰) = terminal/last carbon
  • Most common: Palmitate (C16:0), Stearate (C18:0), Oleate (C18:1), Arachidonate (C20:4)
  • Essential fatty acids (must come from diet): Linoleic acid (Ο‰-6, C18:2) and Ξ±-Linolenic acid (Ο‰-3, C18:3)

3. DIGESTION & ABSORPTION

  • Dietary triglycerides β†’ hydrolyzed by pancreatic lipase (with colipase) β†’ monoglycerides + FFA
  • Bile salts emulsify fat β†’ form micelles for absorption
  • In enterocytes: monoglycerides + FFA β†’ re-synthesized TAG
  • Packaged into chylomicrons β†’ enter lymphatics (thoracic duct) β†’ blood
  • Short-chain fatty acids bypass lymph β†’ enter portal blood directly bound to albumin

4. LIPOPROTEINS β€” HIGH-YIELD TABLE

LipoproteinSourceMain LipidKey ApolipoproteinFunction
ChylomicronIntestineTAG (dietary)Apo B-48Dietary fat β†’ tissues
VLDLLiverTAG (endogenous)Apo B-100Endogenous TAG β†’ tissues
IDLFrom VLDLTAG + CholesterolApo B-100, Apo EIntermediate
LDLFrom IDLCholesterolApo B-100Cholesterol β†’ tissues (atherogenic)
HDLLiver + IntestineProtein-richApo A-IReverse cholesterol transport

Key points:

  • Lipoprotein lipase (LPL): On capillary endothelium; activated by Apo C-II (on chylomicrons and VLDL); hydrolyzes TAG β†’ FFA + glycerol
  • LPL is highest in: adipose tissue, heart, skeletal muscle, lactating mammary gland
  • Hepatic lipase: Removes remaining lipids from IDL β†’ LDL
  • CETP (Cholesteryl Ester Transfer Protein): Transfers cholesterol esters from HDL to VLDL/LDL
  • Chylomicron remnants (after LPL action) β†’ taken up by liver via Apo E receptor
  • LDL receptor binds Apo B-100 and Apo E
  • Half-life of chylomicrons: <1 hour; plasma appears turbid after a fatty meal

5. FATTY ACID OXIDATION (Ξ²-OXIDATION)

Activation & Transport:

  • FFA β†’ Fatty acyl CoA (activation): in cytoplasm; enzyme = Acyl CoA synthetase (thiokinase); costs 2 ATP (ATP β†’ AMP + PPi)
  • Long-chain fatty acyl CoA cannot cross inner mitochondrial membrane β†’ needs carnitine shuttle:
    • Carnitine acyltransferase I (CAT I / CPT-I): outer mitochondrial membrane β€” rate-limiting step
    • Carnitine-acylcarnitine translocase: transports across membrane
    • CPT-II: inner membrane, releases acyl CoA in matrix
  • Malonyl CoA inhibits CPT-I β†’ prevents FA oxidation when synthesis is occurring (fed state)

Ξ²-Oxidation cycle (for each cycle, removes 2 carbons as acetyl CoA):

  1. Acyl CoA dehydrogenase β†’ trans-Δ²-Enoyl CoA + FADHβ‚‚
  2. Enoyl CoA hydratase β†’ L-3-Hydroxyacyl CoA
  3. 3-Hydroxyacyl CoA dehydrogenase β†’ 3-Ketoacyl CoA + NADH
  4. Thiolase β†’ Acetyl CoA + shorter acyl CoA (2C shorter)

Energy yield from palmitate (C16:0):

  • 7 cycles of Ξ²-oxidation β†’ 8 Acetyl CoA, 7 FADHβ‚‚, 7 NADH
  • ATP from 8 Acetyl CoA (Γ— ~10 each via TCA): ~80 ATP
  • 7 FADHβ‚‚ Γ— 1.5 = 10.5; 7 NADH Γ— 2.5 = 17.5 β†’ total β‰ˆ 106 ATP
  • Subtract 2 (activation) = net ~106 ATP

Odd-chain fatty acids:

  • Last product: Propionyl CoA β†’ methylmalonyl CoA (requires vitamin B12 and biotin) β†’ succinyl CoA β†’ enters TCA cycle
  • Deficiency of B12 or methylmalonyl CoA mutase β†’ methylmalonic acidemia

Unsaturated fatty acids:

  • Require isomerase (for cisβ†’trans) and/or reductase (for odd-positioned double bonds); require NADPH
  • Yield slightly less ATP than saturated equivalents

Peroxisomal Ξ²-oxidation:

  • For very long chain fatty acids (VLCFA, >C22)
  • First step: Acyl CoA oxidase (uses Oβ‚‚, produces Hβ‚‚Oβ‚‚ β€” not FADHβ‚‚)
  • Zellweger syndrome = peroxisome biogenesis defect β†’ VLCFA accumulation
  • X-linked adrenoleukodystrophy (ALD) = ABCD1 transporter mutation β†’ VLCFA in adrenals/CNS

6. FATTY ACID SYNTHESIS (DE NOVO)

Overview:

  • Occurs in cytoplasm/cytosol (opposite of Ξ²-oxidation in mitochondria)
  • Main site: Liver (also adipose, lactating mammary gland)
  • Raw material: Acetyl CoA (from glucose via pyruvate β†’ pyruvate dehydrogenase β†’ acetyl CoA)

Acetyl CoA Transport (citrate shuttle):

  • Acetyl CoA is trapped in mitochondria β†’ forms citrate with OAA β†’ citrate crosses into cytosol β†’ cleaved by ATP-citrate lyase β†’ Acetyl CoA + OAA
  • OAA β†’ malate β†’ pyruvate (malic enzyme, generates NADPH) or back to OAA via PEPCK

Key committed step:

  • Acetyl CoA β†’ Malonyl CoA by Acetyl CoA Carboxylase (ACC)
    • Enzyme requires biotin as cofactor
    • Activated by citrate (high energy state)
    • Inhibited by palmitoyl CoA (product inhibition) and by glucagon/epinephrine (phosphorylation inactivates)
    • Activated by insulin (dephosphorylation)
    • This is the rate-limiting step of fatty acid synthesis

Fatty Acid Synthase (FAS):

  • Multienzyme complex; uses NADPH as reductant
  • Adds 2 carbons (from malonyl CoA) per cycle
  • First primer: Acetyl CoA; subsequent additions: malonyl CoA
  • Product: Palmitoyl CoA (C16)
  • Requires 7 malonyl CoA + 1 acetyl CoA + 14 NADPH to make palmitate

Elongation & Desaturation:

  • Palmitate (C16) β†’ longer chains in ER (elongases) or mitochondria
  • Desaturation by mixed-function oxidases (desaturases, e.g., Ξ”9-desaturase) in ER; require Oβ‚‚ and NADH/NADPH
  • Humans cannot introduce double bonds beyond C9 β†’ cannot make linoleic (Ξ”9,12) or Ξ±-linolenic (Ξ”9,12,15) β†’ essential

NADPH sources for FA synthesis:

  1. Pentose phosphate pathway (glucose-6-phosphate dehydrogenase) β€” major source
  2. Malic enzyme (in cytosol)
  3. Isocitrate dehydrogenase (cytosolic)

7. TRIACYLGLYCEROL (TAG) METABOLISM

Synthesis:

  • Glycerol-3-phosphate (from glucose via glycolysis or glycerol via glycerol kinase) + 3 fatty acyl CoA β†’ TAG
  • Key intermediate: Phosphatidic acid (diacylglycerol phosphate)
  • Route: Glycerol-3-P β†’ Lysophosphatidic acid β†’ Phosphatidic acid β†’ DAG (diacylglycerol) β†’ TAG

Lipolysis (TAG breakdown in adipose):

  • Hormone-sensitive lipase (HSL): rate-limiting; activated by glucagon, epinephrine (via cAMP/PKA); inhibited by insulin
  • Adipose Triglyceride Lipase (ATGL): initiates lipolysis (TAG β†’ DAG)
  • Monoacylglycerol lipase: DAG β†’ MAG β†’ glycerol + FFA
  • Released FFA β†’ albumin β†’ liver/muscle; glycerol β†’ liver for gluconeogenesis
  • Perilipin coats lipid droplets; phosphorylated by PKA during lipolysis

8. CHOLESTEROL METABOLISM

Biosynthesis:

  • All 27 carbons of cholesterol derived from acetyl CoA
  • Occurs in cytosol/ER, mainly liver
  • Key pathway: Acetyl CoA β†’ HMG CoA β†’ Mevalonate (rate-limiting step)

Rate-limiting enzyme:

  • HMG CoA reductase (3-hydroxy-3-methylglutaryl CoA reductase)
    • Located in ER
    • Inhibited by: statins (competitive inhibitors), cholesterol itself (feedback), glucagon, AMP (AMPK), bile acids
    • Activated by: insulin, thyroid hormone
    • Diurnal variation: activity highest at midnight (hence statins given at night)

Mevalonate pathway:

  • HMG CoA β†’ Mevalonate (HMG CoA reductase, uses 2 NADPH)
  • Mevalonate β†’ Isopentenyl pyrophosphate (IPP) β†’ Geranyl PP β†’ Farnesyl PP
  • 2 Farnesyl PP β†’ Squalene β†’ Lanosterol β†’ Cholesterol
  • Farnesyl PP also used for: dolichol (N-glycosylation), ubiquinone (CoQ), farnesylation of Ras proteins
  • This explains statin side effects (myopathy from CoQ depletion)

Cholesterol regulation:

  • SREBP (Sterol Regulatory Element Binding Protein) activates LDL receptor and HMG CoA reductase genes when cholesterol is low
  • SCAP senses cholesterol; releases SREBP when cholesterol is low

Cholesterol storage:

  • Esterified by ACAT (Acyl CoA: Cholesterol Acyltransferase) in cells β†’ stored as cholesterol esters
  • In plasma: LCAT (Lecithin:Cholesterol Acyltransferase) esterifies cholesterol on HDL; activated by Apo A-I

Bile acid synthesis:

  • Major route of cholesterol elimination
  • Rate-limiting enzyme: 7Ξ±-hydroxylase (CYP7A1)
  • Primary bile acids: Cholic acid & Chenodeoxycholic acid (conjugated with glycine/taurine)
  • Secondary bile acids: Deoxycholic acid & Lithocholic acid (by gut bacteria)
  • Enterohepatic circulation: ~95% bile acids reabsorbed in terminal ileum
  • Cholestyramine (bile acid sequestrant) interrupts this β†’ forces more cholesterol β†’ bile acids β†’ lowers plasma cholesterol

9. KETONE BODY METABOLISM

Ketogenesis (liver only):

  • Occurs when acetyl CoA accumulates (fasting, diabetes, high-fat diet)
  • Trigger: low OAA (OAA used for gluconeogenesis) β†’ acetyl CoA can't enter TCA β†’ diverted to ketones
  • Steps:
    1. Acetoacetyl CoA (thiolase reversal)
      • Acetyl CoA β†’ HMG CoA (mitochondrial HMG CoA synthase β€” rate-limiting)
    3. HMG CoA β†’ Acetoacetate + Acetyl CoA (HMG CoA lyase)
    4. Acetoacetate β†’ 3-Hydroxybutyrate (NADH as donor; favored when NADH is high)
    5. Acetoacetate β†’ Acetone (spontaneous decarboxylation, detected in breath)
  • Mitochondrial HMG CoA synthase = rate-limiting enzyme of ketogenesis

Ketolysis (peripheral tissues β€” NOT liver):

  • 3-Hydroxybutyrate β†’ Acetoacetate (3-hydroxybutyrate dehydrogenase, NADH produced)
  • Acetoacetate + Succinyl CoA β†’ Acetoacetyl CoA (enzyme: succinyl CoA:acetoacetyl CoA transferase = thiophorase)
  • Liver lacks thiophorase β†’ cannot use ketone bodies
  • Acetoacetyl CoA β†’ 2 Acetyl CoA β†’ TCA β†’ ATP
  • Tissues that use ketones: brain (during starvation), heart, skeletal muscle, kidney

Diabetic Ketoacidosis (DKA):

  • No insulin β†’ massive lipolysis β†’ hepatic FA oxidation β†’ acetyl CoA floods liver β†’ ketogenesis
  • Ketonemia + ketonuria + metabolic acidosis
  • 3-Hydroxybutyrate predominates (increased NADH shifts equilibrium)

10. PHOSPHOLIPID METABOLISM

  • Glycerophospholipids: built on glycerol backbone; e.g., phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylinositol (PI)
  • CDP-choline / CDP-ethanolamine pathway: Key for PC and PE synthesis (Kennedy pathway)
  • Phospholipase A2: cleaves sn-2 position β†’ releases arachidonic acid β†’ prostaglandins, leukotrienes
  • Platelet-activating factor (PAF): acetyl group at sn-2 of phospholipid
  • Sphingomyelin: sphingosine + phosphocholine; abundant in myelin
  • Sphingomyelinase deficiency β†’ Niemann-Pick disease (sphingomyelin accumulation)
  • Ceramide = sphingosine + fatty acid (backbone of sphingolipids)

Sphingolipidoses (lysosomal storage diseases):

DiseaseEnzyme DeficientAccumulated
GaucherGlucocerebrosidaseGlucocerebroside
Niemann-PickSphingomyelinaseSphingomyelin
Tay-SachsHexosaminidase AGM2 ganglioside
FabryΞ±-Galactosidase ACeramide trihexoside
KrabbeGalactocerebrosidaseGalactocerebroside
Metachromatic leukodystrophyArylsulfatase ASulfatide

11. EICOSANOIDS

  • Derived from arachidonic acid (C20:4, Ο‰-6)
  • COX (cyclooxygenase) β†’ prostaglandins, thromboxanes; inhibited by aspirin (irreversible), NSAIDs
  • Lipoxygenase β†’ leukotrienes (mediators of asthma/allergy)
  • TXAβ‚‚ (thromboxane A2): vasoconstriction, platelet aggregation (from platelets)
  • PGIβ‚‚ (prostacyclin): vasodilation, anti-aggregatory (from endothelium) β€” aspirin permanently inhibits COX in platelets
  • Leukotrienes B4 (LTB4): neutrophil chemotaxis; LTC4/D4/E4: bronchoconstriction (slow-reacting substances)

12. DISORDERS OF LIPID METABOLISM

Hyperlipidemias (Fredrickson Classification):

TypeElevatedDefect
IChylomicronsLPL deficiency or Apo C-II deficiency
IIaLDLLDL receptor defect (Familial hypercholesterolemia)
IIbLDL + VLDLβ€”
IIIIDLApo E2/E2 (dysbetalipoproteinemia)
IVVLDLOverproduction of VLDL
VChylomicrons + VLDLLPL deficiency + VLDL excess
  • Familial hypercholesterolemia (FH): LDL receptor mutation β†’ very high LDL β†’ xanthomas, early MI
  • Familial lipoprotein lipase deficiency (Type I): Milky plasma, pancreatitis, eruptive xanthomas; no increased CVD risk
  • Abetalipoproteinemia: No Apo B β†’ no chylomicrons or VLDL; fat malabsorption, acanthocytes, ataxia, retinitis pigmentosa

Fatty acid oxidation defects:

  • MCAD deficiency (Medium-chain acyl CoA dehydrogenase): Most common FA oxidation defect; hypoketotic hypoglycemia during fasting; C8 acylcarnitine on newborn screen
  • Carnitine deficiency: Cannot transport LCFA into mitochondria β†’ cardiomyopathy, muscle weakness, hypoketotic hypoglycemia

13. HORMONAL REGULATION OF LIPID METABOLISM

HormoneEffect on Lipid Metabolism
Insulin↑ FA synthesis (activates ACC), ↑ LPL, ↑ TAG storage, ↓ lipolysis (inhibits HSL)
Glucagon↓ FA synthesis (inhibits ACC), ↑ lipolysis, ↑ ketogenesis
Epinephrine↑ lipolysis (activates HSL via cAMP), ↑ FA oxidation
Cortisol↑ lipolysis (mobilizes FFA), central fat redistribution
Thyroid hormone (T3)↑ HMG CoA reductase, ↑ LDL receptors β†’ lowers LDL
Leptin↑ FA oxidation, ↓ TAG synthesis

14. KEY ENZYMES & COFACTORS β€” HIGH-YIELD TABLE

EnzymeCofactorFunction
Acetyl CoA CarboxylaseBiotinFA synthesis (rate-limiting)
Pyruvate carboxylaseBiotinOAA synthesis
Propionyl CoA carboxylaseBiotinPropionyl CoA β†’ methylmalonyl CoA
Methylmalonyl CoA mutaseVitamin B12Methylmalonyl β†’ succinyl CoA
Fatty Acid SynthaseNADPHElongation of FA chain
HMG CoA reductaseNADPHCholesterol synthesis (rate-limiting)
Mitochondrial HMG CoA synthaseβ€”Ketogenesis (rate-limiting)
7Ξ±-Hydroxylaseβ€”Bile acid synthesis (rate-limiting)
Lipoprotein lipaseβ€”TAG hydrolysis in capillaries; activated by Apo C-II
LCATβ€”Cholesterol esterification on HDL; activated by Apo A-I
ACATβ€”Intracellular cholesterol esterification
Phospholipase A2β€”Releases arachidonic acid from sn-2

15. COMPARTMENTALIZATION β€” CRITICAL FOR MCQs

ProcessLocation
Ξ²-Oxidation (LCFA)Mitochondria
Ξ²-Oxidation (VLCFA)Peroxisomes
Fatty acid synthesisCytosol
Cholesterol synthesisCytosol/ER
KetogenesisMitochondria (liver)
Elongation of FAER (mainly)
Desaturation of FAER
TAG synthesisER
LPL actionCapillary endothelium

16. STATIN PHARMACOLOGY

  • Mechanism: Competitive inhibition of HMG CoA reductase β†’ ↓ cholesterol synthesis β†’ ↑ LDL receptors β†’ ↓ LDL
  • Side effects: Myopathy/rhabdomyolysis (↓ CoQ10), hepatotoxicity
  • Given at night (enzyme activity peaks at midnight)
  • Combined with ezetimibe (blocks NPC1L1 = intestinal cholesterol absorption)

17. REVERSE CHOLESTEROL TRANSPORT

  • HDL (nascent, disc-shaped) ← made by liver/intestine with Apo A-I
  • Cholesterol efflux from cells β†’ HDL via ABCA1 transporter
  • LCAT esterifies free cholesterol on HDL β†’ mature spherical HDL
  • Cholesterol esters on HDL β†’ can be transferred to LDL/VLDL by CETP
  • Final: HDL β†’ SR-BI receptor on liver β†’ cholesterol removed
  • Tangier disease: ABCA1 mutation β†’ very low HDL, cholesterol deposits in tonsils/tissues

⭐ COMMON MCQ TRAPS

  1. Biotin deficiency β†’ impaired FA synthesis (ACC), gluconeogenesis (PC), and propionyl CoA metabolism
  2. B12 deficiency β†’ methylmalonic acidemia (propionyl CoA β†’ methylmalonyl CoA blocked), NOT FA synthesis
  3. Malonyl CoA inhibits CPT-I β†’ fed state = no FA oxidation happening simultaneously
  4. Liver cannot use ketone bodies (lacks thiophorase)
  5. Adipose tissue lacks glycerol kinase β†’ cannot use free glycerol; needs glucose for glycerol-3-P
  6. Chylomicron remnants (not chylomicrons) are taken up by liver
  7. Odd-chain FA β†’ only lipid pathway that contributes to gluconeogenesis (via succinyl CoA/propionyl CoA)
  8. HMG CoA exists in both mitochondria (ketogenesis) and cytosol (cholesterol synthesis) β€” different pools
  9. MCAD deficiency β†’ hypoketotic (not hyperketotic) hypoglycemia
  10. Ezetimibe blocks NPC1L1 (intestinal); bile acid sequestrants prevent reabsorption in ileum β€” both lower LDL
Sources: Lippincott Illustrated Reviews Biochemistry 8e (Chapters 16–18), Guyton & Hall Medical Physiology (Chapter 69)

Tell me everything important related to lipid metabolism, point wise, crisp, got an MCQ test tomorrow. Biochemistry. Make it short.

Lipid Metabolism β€” MCQ Rapid Review

FATTY ACID OXIDATION (Ξ²-Oxidation)

  • Occurs in mitochondria; VLCFA in peroxisomes
  • Activation: FFA β†’ Acyl CoA (costs 2 ATP; ATPβ†’AMP+PPi)
  • Transport into mitochondria: Carnitine shuttle (CPT-I = rate-limiting)
  • Malonyl CoA inhibits CPT-I (fed state blocks oxidation)
  • Each cycle: FADHβ‚‚ + NADH + Acetyl CoA released
  • Odd-chain FA β†’ Propionyl CoA β†’ needs B12 + Biotin β†’ Succinyl CoA (only FA that feeds gluconeogenesis)
  • Peroxisomal first step uses Oβ‚‚ β†’ Hβ‚‚Oβ‚‚ (not FADHβ‚‚)

FATTY ACID SYNTHESIS

  • Occurs in cytosol; mainly liver
  • Acetyl CoA trapped in mitochondria β†’ exits as citrate (citrate shuttle) β†’ cleaved by ATP-citrate lyase
  • Rate-limiting step: Acetyl CoA β†’ Malonyl CoA by Acetyl CoA Carboxylase (ACC)
    • Cofactor: Biotin
    • Activated by: citrate, insulin
    • Inhibited by: palmitoyl CoA, glucagon/epinephrine
  • Fatty Acid Synthase: needs NADPH; makes palmitate (C16)
  • NADPH sources: pentose phosphate pathway (main), malic enzyme
  • Elongation: ER; Desaturation: ER (Ξ”9-desaturase)
  • Essential FA (cannot synthesize): Linoleic (Ο‰-6) and Ξ±-Linolenic (Ο‰-3)

KETONE BODIES

  • Made only in liver mitochondria; used by all peripheral tissues except liver (lacks thiophorase)
  • Triggered by: fasting, DKA, high-fat diet β€” low OAA β†’ acetyl CoA can't enter TCA
  • Steps: Acetoacetyl CoA β†’ HMG CoA (mitochondrial HMG CoA synthase = rate-limiting) β†’ Acetoacetate β†’ 3-Hydroxybutyrate or Acetone
  • 3-Hydroxybutyrate predominates when NADH is high (fasting/DKA)
  • Acetone = volatile, detected on breath
  • DKA: no insulin β†’ lipolysis β†’ ketogenesis β†’ metabolic acidosis

CHOLESTEROL SYNTHESIS

  • All 27 carbons from acetyl CoA; occurs in cytosol/ER
  • Rate-limiting: HMG CoA β†’ Mevalonate by HMG CoA reductase
    • Inhibited by: statins, cholesterol, glucagon, AMPK
    • Activated by: insulin, thyroid hormone
    • Activity peaks at midnight β†’ statins given at night
  • Mevalonate β†’ IPP β†’ Farnesyl PP β†’ Squalene β†’ Cholesterol
  • Farnesyl PP also β†’ CoQ10, dolichol, Ras proteins (explains statin myopathy)
  • SREBP: master regulator; ↑ LDL receptors + HMG CoA reductase when cholesterol is low

LIPOPROTEINS

LipoproteinSourceKey ApoMain lipid
ChylomicronIntestineApo B-48Dietary TAG
VLDLLiverApo B-100Endogenous TAG
LDLFrom IDLApo B-100Cholesterol
HDLLiver/gutApo A-IProtein-rich
  • LPL: activated by Apo C-II; hydrolyzes TAG in capillaries
  • Chylomicron remnants (not intact chylomicrons) taken up by liver via Apo E
  • LCAT: esterifies cholesterol on HDL; activated by Apo A-I
  • CETP: transfers cholesterol esters from HDL β†’ LDL/VLDL
  • ABCA1: cholesterol efflux from cells β†’ HDL (defective in Tangier disease)

LIPOLYSIS (Adipose)

  • ATGL: TAG β†’ DAG (initiates)
  • HSL: DAG β†’ MAG (rate-limiting); activated by glucagon/epinephrine (cAMPβ†’PKA); inhibited by insulin
  • Released glycerol β†’ liver (gluconeogenesis); FFA β†’ albumin β†’ liver/muscle
  • Adipose lacks glycerol kinase β†’ needs glucose for glycerol-3-P (TAG re-synthesis)

BILE ACIDS

  • Rate-limiting: 7Ξ±-hydroxylase
  • Primary: Cholic + Chenodeoxycholic acid; Secondary (gut bacteria): Deoxycholic + Lithocholic
  • 95% reabsorbed at terminal ileum (enterohepatic circulation)
  • Cholestyramine blocks reabsorption β†’ forces cholesterol β†’ bile acids β†’ ↓ LDL

DISORDERS β€” RAPID TABLE

DiseaseDefectKey Feature
Familial hypercholesterolemiaLDL receptorVery high LDL, xanthomas, early MI
Type I hyperlipidemiaLPL or Apo C-II deficiencyMilky plasma, pancreatitis, no ↑CVD
MCAD deficiencyMedium-chain acyl CoA DHHypoketotic hypoglycemia
AbetalipoproteinemiaNo Apo BFat malabsorption, acanthocytes, ataxia
ZellwegerPeroxisome biogenesisVLCFA accumulation
Tangier diseaseABCA1 mutationVery low HDL, cholesterol in tonsils

SPHINGOLIPIDOSES

DiseaseEnzymeAccumulates
GaucherGlucocerebrosidaseGlucocerebroside
Niemann-PickSphingomyelinaseSphingomyelin
Tay-SachsHexosaminidase AGM2 ganglioside
FabryΞ±-Galactosidase ACeramide trihexoside
KrabbeGalactocerebrosidaseGalactocerebroside

⭐ MCQ TRAPS

  1. Biotin deficiency β†’ impairs ACC (FA synthesis), PC (gluconeogenesis), propionyl CoA carboxylase
  2. B12 deficiency β†’ methylmalonic acidemia (not FA synthesis)
  3. Liver cannot use ketone bodies (no thiophorase)
  4. Malonyl CoA inhibits CPT-I β†’ fed state prevents simultaneous FA oxidation
  5. Adipose no glycerol kinase β†’ can't salvage glycerol
  6. HMG CoA exists in mitochondria (ketogenesis) AND cytosol (cholesterol) β€” different compartments
  7. MCAD = hypoketotic hypoglycemia (not hyperketotic)
  8. Odd-chain FA only β†’ contributes carbon to gluconeogenesis
  9. Chylomicrons enter lymph, not portal blood (except short-chain FA)
  10. Ezetimibe blocks NPC1L1 (intestinal absorption); statins block synthesis

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