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Steroids are a large family of biologically important molecules derived from a cyclopentanoperhydrophenanthrene nucleus, also called the steroid nucleus or sterane nucleus.
Four fused rings: A, B, C (six-membered) and D (five-membered)
Rings are numbered from A → D
Major natural steroids include:
Cholesterol
Steroid hormones (cortisol, aldosterone, estrogen, testosterone)
Bile acids
Vitamin D
Maintain cell membrane structure (cholesterol)
Act as hormones regulating metabolism, salt-water balance, and reproduction
Aid in digestion (bile salts)
Regulate calcium levels (vitamin D)
Cholesterol is the parent compound for almost all steroids.
Cholesterol is a 27-carbon steroid alcohol.
It contains the classic four-ring steroid structure + hydrocarbon tail.
Steroid nucleus
Rings A, B, C, D fused together
Provides rigid, planar structure
Hydroxyl group at C-3
Makes cholesterol a sterol
Allows ester formation (cholesteryl esters)
Double bond between C-5 and C-6
Important for rigidity and membrane behavior
Eight-carbon hydrocarbon side chain attached at C-17
Site needed for conversion to bile acids
Methyl groups at C-10 and C-13
Amphipathic (has both polar and non-polar parts)
Poorly soluble in water
Transported in blood via lipoproteins
Precursor for multiple steroid products
Maintains fluidity at body temperature
Prevents membranes from becoming too rigid or too fluid
Interacts with phospholipids and sphingolipids
Parent molecule for:
Corticosteroids (cortisol, aldosterone)
Sex hormones (estrogen, progesterone, testosterone)
Bile acids (cholic acid, chenodeoxycholic acid)
Vitamin D synthesis (cholecalciferol)
Structural component of cell membranes
Required for lipid raft formation
Cholesterol is synthesized mainly in the liver, and to some extent in intestine, adrenal cortex, testes, ovaries.
Synthesis occurs in the cytosol and smooth endoplasmic reticulum (SER).
The entire pathway is built from Acetyl-CoA.
Cholesterol synthesis occurs in four major stages:
Formation of HMG-CoA
Formation of Mevalonate (rate-limiting)
Formation of Isoprenoid units → Squalene
Conversion of Squalene → Lanosterol → Cholesterol
2 Acetyl-CoA → Acetoacetyl-CoA
Enzyme: Thiolase
Acetoacetyl-CoA + Acetyl-CoA → HMG-CoA (3-hydroxy-3-methylglutaryl-CoA)
Enzyme: HMG-CoA synthase (cytosolic)
Note: This is NOT the same enzyme used in ketogenesis (mitochondrial isoform).
HMG-CoA → Mevalonate
Enzyme: HMG-CoA reductase
Requires 2 NADPH
This is the rate-limiting, highly regulated step in the entire pathway.
Statins (lovastatin, atorvastatin, simvastatin)
→ competitively inhibit HMG-CoA reductase
→ ↓ cholesterol synthesis in liver.
Mevalonate undergoes three sequential phosphorylations, forming:
5-phosphomevalonate
5-pyrophosphomevalonate (activated)
5-Pyrophosphomevalonate → Isopentenyl pyrophosphate (IPP)
→ a 5-carbon “isoprene unit”
IPP ↔ Dimethylallyl pyrophosphate (DMAPP)
IPP + DMAPP → Geranyl-PP (10-carbon)
Geranyl-PP + IPP → Farnesyl-PP (15-carbon)
Two farnesyl-PP combine to form:
→ Squalene (30-carbon linear molecule)
Requires NADPH.
Squalene → Squalene-2,3-epoxide
(oxygen + NADPH dependent)
Squalene epoxide → Lanosterol
This is the first steroid ring structure.
Lanosterol undergoes:
Demethylation (removal of 3 methyl groups)
Double bond rearrangements
Side chain modifications
→ Final product: Cholesterol (27-carbons)
Cholesterol synthesis is energy expensive:
18 ATP used
14 NADPH used
This explains why high-calorie states promote cholesterol synthesis.
Insulin
Thyroxine
High carbohydrate diet
Low intracellular cholesterol
Glucagon
Cholesterol (end-product inhibition)
Statin drugs
High intracellular cholesterol → SREBP suppression
AMP-activated protein kinase (AMPK)
(during fasting, exercise, low energy)
Inhibits HMG-CoA reductase → ↓ hepatic cholesterol → ↑ LDL receptor expression → ↓ plasma LDL.
Deficiency of 7-dehydrocholesterol reductase
→ low cholesterol → multiple congenital anomalies.
Due to defective LDL receptor or ApoB → high LDL → early atherosclerosis.
Cholesterol synthesized in cytosol + SER
HMG-CoA reductase is rate limiting
Statins inhibit HMG-CoA reductase
NADPH from HMP shunt is required
Final structure formed through lanosterol
Plasma lipids circulate in blood in association with proteins as lipoproteins.
The major plasma lipids are:
Main storage form of fat
Present in chylomicrons and VLDL
Hydrophobic → require transport in lipoproteins
Exists as free cholesterol and cholesteryl esters
Precursor of bile acids, steroid hormones, vitamin D
Excess → atherosclerosis
Amphipathic
Form structural component of lipoprotein surface
Essential for cell membrane integrity
Released from adipose tissue during fasting
Carried by albumin
Quickly taken up by liver & muscle for oxidation
Since lipids are hydrophobic, they cannot travel freely in blood.
They are transported in two major ways:
This is the major mechanism.
Dietary and endogenous lipids are packaged into lipoproteins, which circulate in plasma.
Functions:
Deliver dietary fat → tissues
Deliver liver-synthesized TAG → tissues
Return cholesterol → liver
Maintain lipid homeostasis
Free fatty acids are transported bound to serum albumin after lipolysis during fasting.
Lipoproteins are spherical particles that transport lipids in blood.
They contain:
Core: TAGs + cholesteryl esters
Surface: phospholipids + free cholesterol + apolipoproteins
They differ in:
Density
Size
Lipid composition
Function
Apolipoprotein content
From largest → smallest (lowest → highest density):
Largest, least dense
Highest TAG content
Transport dietary TAGs from intestine to tissues
Produced by liver
Transports endogenous TAGs to tissues
Intermediate remnant of VLDL metabolism
Rich in cholesterol
Delivers cholesterol to tissues
“Bad cholesterol” because high LDL → atherosclerosis
Smallest, most dense
Rich in proteins
Responsible for reverse cholesterol transport
“Good cholesterol”
Carry dietary TAGs from intestine → muscle & adipose
Remnants are taken up by liver
Carry liver-synthesized TAGs → peripheral tissues
Transitional form → converted to LDL
Supplies cholesterol to all cells
Taken up by LDL receptors
Collects cholesterol from tissues
Transfers cholesterol to liver for disposal
Contains LCAT (lecithin:cholesterol acyltransferase)
Apolipoproteins are protein components of lipoproteins.
They serve as:
Structural components
Enzyme activators
Ligands for receptors
Found mainly in HDL
Activates LCAT
Essential for reverse cholesterol transport
Found in chylomicrons
Required for their assembly in intestine
Present in VLDL, IDL, LDL
Ligand for LDL receptor
Needed for hepatic lipoprotein secretion
Activator of Lipoprotein Lipase (LPL)
Required for TAG breakdown in chylomicrons & VLDL
Inhibits LPL
Delays TAG clearance → high triglycerides
Present on chylomicron remnants, VLDL remnants, HDL
Ligand for ApoE receptor / remnant receptor
Required for hepatic uptake of remnants
Present in Lipoprotein(a)
Structural analog of plasminogen
High levels → increased risk of atherosclerosis & thrombosis
Chylomicrons: Apo B-48, A, C, E
VLDL: Apo B-100, C, E
LDL: Apo B-100
HDL: Apo A-I, A-II, C, E
Defective LDL receptor or Apo B-100
Very high LDL
Early atherosclerosis, xanthomas
Remnant accumulation
High chylomicron remnants & IDL
Palmar xanthomas
No Apo B → no chylomicrons/VLDL
Fat malabsorption, acanthocytosis, neurological defects
No LPL activation
Severe hypertriglyceridemia
Plasma lipids = TAG, cholesterol, cholesteryl ester, phospholipids, FFAs
Lipoproteins transport insoluble lipids
Chylomicrons → dietary TAGs
VLDL → endogenous TAGs
LDL → cholesterol to tissues
HDL → cholesterol back to liver
Apolipoproteins regulate metabolism & receptor interaction
Chylomicrons are the largest, least dense lipoproteins.
Their main function is to transport dietary triacylglycerols (TAGs) from the intestine to peripheral tissues.
Very high TAG (85–90%)
Small amounts of cholesterol & phospholipids
Major apolipoproteins:
Apo B-48 (structural; unique to intestine)
Apo C-II (activates LPL)
Apo E (required for remnant uptake by liver)
Synthesized in intestinal mucosal cells
Assembled by microsomal triglyceride transfer protein (MTP)
Chylomicrons enter lymph → blood
Apo C-II activates LPL in adipose & muscle
TAGs are hydrolyzed → FFAs + glycerol
Particle shrinks → chylomicron remnant
Remnant taken up by liver via Apo E receptor
Type I Hyperlipoproteinemia:
LPL deficiency or Apo C-II deficiency → huge chylomicron accumulation → pancreatitis
Abetalipoproteinemia:
No Apo B → no chylomicrons.
VLDL transports endogenously synthesized TAGs from the liver to peripheral tissues.
TAG-rich (but less than chylomicrons)
Contains:
Apo B-100
Apo C-II
Apo E
Deliver liver TAG to adipose & muscle
After TAG removal by LPL → becomes IDL
Liver secretes VLDL
LPL removes TAG → particle becomes IDL
IDL has two fates:
Taken up by liver (via Apo E)
Converted to LDL (by losing Apo E & TAG)
Increased in obesity, diabetes, alcohol excess
High VLDL → high triglycerides
Type IV Hyperlipoproteinemia: VLDL excess.
LDL is the major cholesterol-carrying lipoprotein in blood.
It delivers cholesterol to all tissues.
High cholesterol & cholesteryl esters
Apo B-100 only
Supply cholesterol for:
Membranes
Steroid hormones
Bile acids
Formed from IDL
Taken up by LDL receptors via Apo B-100
Degraded in lysosomes
“Bad cholesterol”
High LDL → atherosclerosis
Familial hypercholesterolemia (LDL receptor defect):
Very high LDL
Premature coronary artery disease
Tendon xanthomas
Inhibit HMG-CoA reductase → ↓ hepatic cholesterol
↑ LDL receptor expression → ↓ LDL levels.
HDL is the smallest, densest, most protein-rich lipoprotein.
Reverse cholesterol transport
Collects free cholesterol from tissues
Esterifies it via LCAT (activated by Apo A-I)
Transfers cholesteryl esters to VLDL/LDL or transports to liver
High protein
Apo A-I (main), Apo A-II, Apo C, Apo E
“Good cholesterol”
High HDL → protective against heart disease
Low HDL seen in metabolic syndrome, smoking, diabetes.
Lp(a) is an LDL-like particle with an additional protein called Apo(a) attached to Apo B-100.
LDL particle + Apo(a)
Apo(a) resembles plasminogen
Not fully understood
Associated with:
Atherosclerosis
Thrombosis (because Apo(a) competes with plasminogen → inhibits fibrinolysis)
High Lp(a) = strong independent risk factor for:
Myocardial infarction
Stroke
Levels genetically determined
Niacin reduces Lp(a) levels; statins do not.
FFAs are non-esterified fatty acids released from adipose tissue during fasting.
Breakdown of TAGs in adipose tissue by Hormone-Sensitive Lipase (HSL)
Circulate in blood bound to albumin
Important fuel during fasting
Used by liver, muscle, heart
Liver converts excess FFAs to:
Acetyl-CoA
Ketone bodies (fasting state)
Elevated FFAs → insulin resistance
Very high FFAs in uncontrolled diabetes due to ↑ lipolysis
FFAs are the main substrate for ketogenesis
Chylomicrons → dietary TAGs (Apo B48, C-II, E)
VLDL → endogenous TAGs (Apo B100, C-II, E)
IDL → intermediate, remnant form
LDL → cholesterol to tissues (Apo B100)
HDL → reverse cholesterol transport (Apo A-I)
Lp(a) → LDL + Apo(a) → thrombosis risk
Free fatty acids → transported by albumin, used in fasting
(Also called Free Fatty Acids — FFA)
Non-esterified fatty acids are fatty acids not bound to glycerol. They circulate directly in the bloodstream, especially during fasting.
They are produced when adipose tissue TAGs break down via Hormone-Sensitive Lipase (HSL).
Low insulin
High glucagon
Epinephrine
Cortisol
NEFAs are hydrophobic, so they circulate bound to albumin.
One molecule of albumin can bind multiple FFAs.
During fasting or uncontrolled diabetes, FFAs in blood rise sharply.
After entering tissues:
Liver
Muscle
Heart
→ undergo β-oxidation → acetyl-CoA → TCA or ketogenesis.
In fed states or in liver → converted back to TAGs and packed into VLDL.
Elevated NEFA in uncontrolled diabetes → increased ketone body production.
High FFAs contribute to insulin resistance in metabolic syndrome.
High NEFA in prolonged fasting → liver shifts to ketogenesis.
Bile salts are amphipathic derivatives of cholesterol that aid digestion and absorption of lipids.
Cholesterol → Primary bile acids
Cholic acid
Chenodeoxycholic acid
These combine with:
Glycine → glycocholic acid
Taurine → taurocholic acid
→ forming bile salts (more water-soluble than acids).
Break large fat droplets into smaller ones
Increase surface area for pancreatic lipase
Essential for absorption of:
Fatty acids
Monoglycerides
Cholesterol
Fat-soluble vitamins (A, D, E, K)
Major pathway for removing cholesterol from the body.
95% of bile salts are reabsorbed from the ileum
Returned to liver
Re-secreted in bile
This cycle repeats multiple times per meal.
Cholestyramine (bile acid binding resin) increases fecal loss of bile salts → lowers cholesterol.
Ileal disease (Crohn’s) → bile salt malabsorption → steatorrhea, fat-soluble vitamin deficiency.
Gallstones form when cholesterol exceeds bile salt capacity.
Steroid hormones are cholesterol-derived hormones produced by the adrenal cortex, gonads, and placenta.
All share the cyclopentanoperhydrophenanthrene (steroid) nucleus.
Produced in adrenal cortex (zona fasciculata)
Functions:
Raises blood glucose (gluconeogenesis)
Anti-inflammatory
Catabolic effects on muscle
Maintains vascular tone
Produced in adrenal cortex (zona glomerulosa)
Functions:
Increases Na⁺ reabsorption
Increases K⁺ & H⁺ excretion
Regulates blood pressure & fluid balance
Testosterone (testes)
Dihydrotestosterone (DHT — more potent)
Estradiol, estrone (ovaries)
Prepares uterus for implantation
Maintains pregnancy
Cholesterol → Pregnenolone →
→ Progesterone (branch point)
Glucocorticoids (cortisol)
Mineralocorticoids (aldosterone)
Androgens → Estrogens
Occurs in mitochondrial + ER enzymes.
Steroid hormones bind to intracellular receptors → receptor-hormone complex binds DNA → regulates gene transcription.
Slow onset, long duration.
Cushing syndrome → excess cortisol
Addison disease → deficiency of adrenal steroids
Hyperaldosteronism → hypertension, hypokalemia
Polycystic ovary syndrome (PCOS) → increased androgens
Aromatase inhibitors used in estrogen-dependent breast cancer therapy.
| Topic | Key Facts |
|---|---|
| NEFA | Released from adipose by HSL, transported by albumin, used in fasting |
| Bile salts | Derived from cholesterol, emulsify fat, form micelles, enterohepatic recycling |
| Steroid hormones | Cholesterol-derived; include cortisol, aldosterone, estrogen, progesterone, testosterone |
All steroids share the cyclopentanoperhydrophenanthrene nucleus.
Cholesterol is a 27-carbon sterol with a hydroxyl group at C-3.
Cholesterol is precursor of bile acids, steroid hormones, vitamin D.
Cholesterol is an essential membrane component (regulates fluidity).
Cholesterol synthesis occurs in cytosol + SER of liver.
Begins with acetyl-CoA.
Rate-limiting enzyme = HMG-CoA reductase.
Statins competitively inhibit HMG-CoA reductase → ↓ hepatic cholesterol.
Mevalonate → isoprenoids → squalene → lanosterol → cholesterol.
Requires 18 ATP + 14 NADPH.
Activated by insulin, inhibited by glucagon & cholesterol.
Plasma lipids include TAG, cholesterol, cholesteryl esters, phospholipids, FFAs.
They are transported in blood mainly as lipoproteins.
TAGs & cholesterol are transported via lipoproteins (chylomicrons, VLDL, LDL, HDL).
Free fatty acids travel bound to albumin.
Bile salts are essential for absorption of dietary lipids.
Larger lipoprotein ⇒ lower density (more TAG, less protein).
Smaller lipoprotein ⇒ higher density (more protein, less TAG).
Order:
Chylomicron > VLDL > IDL > LDL > HDL
Transport dietary TAGs from intestine to tissues.
Contain Apo B-48, Apo C-II, Apo E.
Hydrolyzed by LPL (activated by Apo C-II).
Remnants taken up by liver via Apo E.
LPL or Apo C-II deficiency → Type I hyperlipoproteinemia.
Transport endogenous TAGs from liver to tissues.
Contain Apo B-100, C-II, E.
Converted → IDL → LDL.
High VLDL = high triglycerides (seen in obesity, diabetes, alcohol use).
Carries 70% of plasma cholesterol.
Contains Apo B-100.
Delivers cholesterol to tissues via LDL receptor.
High LDL → atherosclerosis (“bad cholesterol”).
Familial hypercholesterolemia = defective LDL receptor.
Smallest, densest lipoprotein; very high protein content.
Contains Apo A-I, A-II, C, E.
Performs reverse cholesterol transport.
LCAT activated by Apo A-I esterifies cholesterol.
High HDL = protective against heart disease.
LDL particle with Apo(a) attached.
Apo(a) is similar to plasminogen → inhibits fibrinolysis.
High Lp(a) = independent risk factor for heart attack & stroke.
Genetically determined; statins DO NOT lower Lp(a).
Apo B-48 → chylomicron assembly.
Apo B-100 → VLDL/LDL secretion + LDL receptor binding.
Apo C-II → activates LPL (TAG hydrolysis).
Apo C-III → inhibits LPL (↑ triglycerides).
Apo E → remnant uptake by liver.
Apo A-I → activates LCAT (HDL maturation).
Released from adipose by Hormone-Sensitive Lipase during fasting.
Transported in blood bound to albumin.
Oxidized via β-oxidation → ATP or ketone body formation.
High FFAs → insulin resistance in metabolic syndrome.
Synthesized from cholesterol in the liver.
Primary bile acids = cholic acid & chenodeoxycholic acid.
Conjugated with glycine/taurine → bile salts.
Functions:
Emulsify fats
Form micelles
Absorb fat-soluble vitamins
Recycled via enterohepatic circulation.
All steroid hormones are derived from cholesterol through pregnenolone.
Glucocorticoids (cortisol) → gluconeogenesis, stress response
Mineralocorticoids (aldosterone) → Na⁺ retention, K⁺ excretion
Sex steroids
Androgens → testosterone, DHT
Estrogens → estradiol
Progesterone → pregnancy maintenance
Synthesized in adrenal cortex, gonads, placenta.
Act via intracellular receptors → regulate gene expression.
Slow onset, long duration of action.
Apo C-II activates LPL — essential for TAG breakdown.
Apo A-I activates LCAT — cholesterol esterification in HDL.
Apo B-48 = chylomicrons, Apo B-100 = VLDL/LDL.
LDL delivers cholesterol; HDL removes cholesterol.
Statins inhibit HMG-CoA reductase → ↓ cholesterol synthesis.
Lp(a) resembles plasminogen → thrombosis risk.
Chylomicron remnants enter liver via Apo E receptor.
HDL performs reverse cholesterol transport.
Free fatty acids travel with albumin during fasting.
Bile salts are essential for fat digestion & absorption.
The cyclopentanoperhydrophenanthrene nucleus.
A 27-carbon sterol with a hydroxyl group at C-3.
In the cytosol and smooth ER, mainly in the liver.
HMG-CoA reductase.
Statins (e.g., atorvastatin, simvastatin).
Membrane fluidity
Precursor of bile acids, steroid hormones, vitamin D
Component of lipoproteins
Cholic acid and chenodeoxycholic acid.
Emulsification of fats and micelle formation for lipid absorption.
Reabsorption of 95% of bile salts from the ileum back to the liver.
TAGs, cholesterol, cholesteryl esters, phospholipids, and free fatty acids.
Because they are hydrophobic; require transport in soluble particles.
Chylomicrons.
Apo B-48.
Lipoprotein lipase (LPL).
Apo C-II.
Mediates uptake of remnants by the liver.
Endogenous TAGs synthesized in the liver.
Intermediate-density lipoprotein; remnant of VLDL.
The major cholesterol-carrying lipoprotein in plasma.
Apo B-100.
High LDL → atherosclerosis due to cholesterol deposition.
Reverse cholesterol transport from tissues back to liver.
LCAT (lecithin–cholesterol acyltransferase).
High HDL → protective against cardiovascular disease.
An LDL particle attached to Apo(a).
Apo(a) resembles plasminogen → inhibits fibrinolysis → ↑ thrombosis risk.
Albumin.
During fasting, exercise, and uncontrolled diabetes (↑ lipolysis).
Hormone-Sensitive Lipase (HSL).
Glucagon & epinephrine (via cAMP).
Insulin.
Glucocorticoids, mineralocorticoids, sex steroids.
Pregnenolone, derived from cholesterol.
Adrenal cortex, gonads, placenta.
Bind intracellular receptors → gene transcription → protein synthesis.
↓ hepatic cholesterol → ↑ LDL receptors → ↑ LDL clearance.
Defective LDL receptor → very high LDL → premature atherosclerosis.
Chylomicrons (due to LPL or Apo C-II deficiency).
VLDL (endogenous hypertriglyceridemia).
Chylomicrons.
A. Acyl-CoA nucleus
B. Cyclopentanoperhydrophenanthrene nucleus
C. Cholesteryl nucleus
D. Pyridine nucleus
Answer: B
Explanation: All steroids share this four-ring nucleus.
A. HMG-CoA synthase
B. Squalene epoxidase
C. HMG-CoA reductase
D. Lanosterol demethylase
Answer: C
Explanation: Converts HMG-CoA → mevalonate; target of statins.
A. Kidney
B. Brain
C. Liver
D. Pancreas
Answer: C
A. Squalene synthase
B. HMG-CoA reductase
C. LCAT
D. LDL receptor
Answer: B
A. LDL
B. HDL
C. Chylomicrons
D. VLDL
Answer: C
A. Chylomicrons
B. LDL
C. HDL
D. Lp(a)
Answer: A
A. Apo A-I
B. Apo C-II
C. Apo B-100
D. Apo E
Answer: B
A. Adipose tissue
B. Liver
C. Intestine
D. Pancreas
Answer: B
A. Apo B-48
B. Apo A-I
C. Apo C-II
D. Apo B-100
Answer: D
A. HDL
B. LDL
C. Chylomicrons
D. VLDL
Answer: B
A. LPL
B. ACAT
C. LCAT
D. CETP
Answer: C
Explanation: Activated by Apo A-I.
A. LDL
B. HDL
C. VLDL
D. Chylomicrons
Answer: B
A. HDL
B. LDL
C. Albumin
D. VLDL
Answer: C
A. TAG
B. Phospholipids
C. Cholesterol
D. Free fatty acids
Answer: C
A. Deoxycholic acid
B. Lithocholic acid
C. Cholic acid
D. Stearic acid
Answer: C
Explanation: Cholic & chenodeoxycholic = primary bile acids.
A. Apo C-II
B. Albumin
C. Plasminogen
D. Ferritin
Answer: C
Explanation: Apo(a) resembles plasminogen → thrombotic risk.
A. COPD
B. Pancreatitis
C. Atherosclerosis & thrombosis
D. Liver cirrhosis
Answer: C
A. Insulin
B. Cortisol
C. Glucagon
D. Thyroxine
Answer: C
Explanation: Fasting → glucagon → cAMP → HSL activation.
A. LCAT
B. HSL
C. LPL
D. CETP
Answer: B
Explanation: Insulin inhibits lipolysis.
A. Apo A-I
B. Apo C-III
C. Apo E
D. Apo B-48
Answer: C
A. HDL
B. Chylomicron remnants
C. LDL
D. VLDL
Answer: C
A. HDL
B. LDL
C. VLDL
D. Chylomicron
Answer: A
A. Apo A-I
B. LDL receptor
C. LCAT
D. CETP
Answer: B
A. Apo A-I
B. Apo C-II
C. Apo C-III
D. Apo E
Answer: C
A. Steroid hormones
B. Bile salts
C. Vitamin D
D. Catecholamines
Answer: D
Explanation: Catecholamines come from tyrosine.
A 7-year-old child presents with recurrent abdominal pain and eruptive xanthomas. A blood sample left overnight forms a thick creamy layer on top.
TAG levels = >2000 mg/dL
Type I Hyperlipoproteinemia
LPL deficiency or
Apo C-II deficiency
Marked accumulation of chylomicrons.
A 25-year-old man presents with MI. Physical exam shows tendon xanthomas over Achilles tendon. LDL > 300 mg/dL.
Familial Hypercholesterolemia (Type IIa)
LDL receptor deficiency
Or Apo B-100 defect
Markedly high LDL → premature atherosclerosis.
A patient has milky plasma after a high-fat meal. Fasting sample returns to normal.
TAG after meal = very high.
VLDL = normal.
Accumulation of chylomicrons (post-prandial)
Delayed or insufficient LPL activity.
A 40-year-old non-obese man has LDL = 240 mg/dL but triglycerides normal.
Type IIa Hyperlipoproteinemia
LDL receptor → impaired LDL clearance.
A 50-year-old diabetic man comes after prolonged fasting. He has dehydration, fruity breath, and Kussmaul breathing.
Diabetic ketoacidosis
Low insulin → ↑ HSL
↑ NEFA to liver
Excess acetyl-CoA → ketogenesis
A 35-year-old has palmar xanthomas and tuberoeruptive xanthomas. TAG moderately elevated.
Type III Hyperlipoproteinemia (Familial dysbetalipoproteinemia)
Apo E deficiency
Accumulation of IDL + chylomicron remnants
5-year-old child has chronic diarrhea, acanthocytosis on blood smear, absence of chylomicrons after meals.
Abetalipoproteinemia
Absence of Apo B (both B-48 and B-100)
No chylomicrons
No VLDL
Fat malabsorption
A 35-year-old uncontrolled diabetic has abdominal pain.
TAG = 900 mg/dL, ketones present.
Hypertriglyceridemia (Type IV) due to ↑ VLDL
Insulin deficiency → ↑ HSL → ↑ NEFA → liver converts to VLDL.
A 48-year-old man with central obesity and insulin resistance shows HDL = 28 mg/dL.
Low HDL due to metabolic syndrome
Chronic inflammation
Increased TAG exchange → HDL depletion
Reduced Apo A-I synthesis
A patient who underwent ileal surgery develops bulky, oily stools.
Bile salt malabsorption → steatorrhea
Ileum is site of bile salt reabsorption (enterohepatic circulation).
A 45-year-old man with no diabetes or obesity presents with MI.
Lipid profile:
LDL: 115 mg/dL (near normal)
HDL: 55 mg/dL
Lp(a): very high
Lp(a)-associated premature atherosclerosis
Apo(a) competes with plasminogen → ↓ fibrinolysis → ↑ thrombosis.
A 3-month-old infant has salt-wasting, dehydration, low cortisol, low aldosterone.
Defect in steroid hormone synthesis
Cholesterol → precursor for all steroid hormones.
A 55-year-old with high LDL is started on a statin. LDL decreases significantly after 6 weeks.
Statins ↓ HMG-CoA reductase
↓ hepatic cholesterol
↑ LDL receptor expression
↑ LDL clearance
A 42-year-old alcoholic develops fatty liver.
Liver biopsy: fat accumulation within hepatocytes.
Alcohol → ↑ NADH
NADH inhibits β-oxidation
Leads to ↑ TAG synthesis and accumulation
A 40-year-old woman develops right-upper-quadrant pain. Ultrasound shows gallstones.
Excess cholesterol in bile
Insufficient bile salts → precipitation
Causing cholesterol stones
A 30-year-old with persistently high LDL despite maximal statin therapy.
Familial hypercholesterolemia (receptor-negative subtype)
Statins do not work well when LDL receptors are absent.
A stressed individual has elevated cortisol levels.
TAG breakdown increases.
Cortisol enhances HSL activity → ↑ NEFA release → ↑ VLDL synthesis.
Likely cause: cholesterol synthesis disorder (7-dehydrocholesterol defect).
Vitamin D precursor is derived from cholesterol in skin.
The cyclopentanoperhydrophenanthrene nucleus.
27 carbons.
A hydroxyl group at carbon 3 (C-3).
In the cytosol and smooth endoplasmic reticulum, mainly in the liver.
HMG-CoA reductase.
Conversion of HMG-CoA to mevalonate.
Pregnenolone (from cholesterol).
Cholic acid and chenodeoxycholic acid.
They emulsify fats and help form micelles for lipid absorption.
Recycling of bile salts from the ileum → portal blood → liver.
TAGs, cholesterol, cholesteryl esters, phospholipids, and free fatty acids.
Because they are hydrophobic and cannot circulate freely.
Chylomicrons.
Apo B-48.
Apo C-II.
Hydrolyses TAGs in chylomicrons and VLDL into FFAs + glycerol.
VLDL.
Intermediate-density lipoprotein; VLDL remnant.
LDL.
Apo B-100.
Because high LDL leads to cholesterol deposition in arteries → atherosclerosis.
HDL.
Reverse cholesterol transport (from tissues → liver).
LCAT.
LDL + Apo(a).
Apo(a) resembles plasminogen → inhibits fibrinolysis → ↑ thrombosis.
Bound to albumin.
During fasting, exercise, and uncontrolled diabetes due to ↑ HSL activity.
Hormone-Sensitive Lipase (HSL).
Insulin.
Steroid hormones.
Glucocorticoids, mineralocorticoids, and sex steroids.
Cortisol.
Regulates Na⁺ retention, K⁺ excretion, and blood pressure.
Bind intracellular receptors, then alter gene transcription.
Accumulation of chylomicrons.
Defective LDL receptor or Apo B-100.
Chylomicrons.
HDL.
They reduce hepatic cholesterol → liver pulls more LDL from blood.
Flowchart 1: Chylomicron Metabolism
Dietary Fat → Intestinal Lumen
↓ (Bile salts emulsify)
Fatty acids + 2-MAG absorbed by enterocytes
↓
Re-esterified → TAG
↓
Chylomicron Assembly (Apo B-48)
↓
Chylomicrons enter lymph → blood
↓
HDL donates Apo C-II + Apo E
↓
Apo C-II activates LPL on capillary endothelium
↓
LPL hydrolyses TAG → FFA + Glycerol
↓
FFA go to muscle (energy) or adipose (storage)
↓
Chylomicron shrinks → becomes Chylomicron Remnant
↓
Apo C-II is returned to HDL
↓
Remnant (with Apo E + B-48) taken up by liver
↓
Hepatic uptake via Apo E receptor
Liver synthesizes TAG
↓
VLDL Assembly (Apo B-100)
↓
VLDL secreted into blood
↓
HDL donates Apo C-II + Apo E
↓
Apo C-II activates LPL → hydrolyses TAG
↓
FFAs taken up by muscle & adipose
↓
VLDL loses TAG → becomes IDL (VLDL remnant)
↓
Two possible pathways:
PATHWAY A:
IDL (with Apo E) taken up by liver
↓
Hepatic remnant receptor clears IDL
PATHWAY B:
IDL loses Apo E + more TAG via hepatic lipase
↓
IDL becomes LDL (rich in cholesterol)
↓
LDL delivers cholesterol to tissues via Apo B-100
↓
LDL taken up by LDL receptors
↓
Excess LDL → atherosclerosis
⭐ Flowchart 3: Reverse Cholesterol Transport (HDL Pathway)
HDL synthesized in liver & intestine
↓
Nascent HDL (discoid shape; Apo A-I) enters blood
↓
HDL picks up free cholesterol from peripheral tissues
↓
Apo A-I activates LCAT
↓
LCAT esterifies cholesterol → cholesteryl esters
↓
HDL matures (spherical HDL3 → HDL2)
↓
Two pathways:
PATHWAY A:
HDL2 delivers cholesteryl esters directly to liver
↓
SR-B1 receptor mediates uptake
PATHWAY B:
HDL transfers cholesteryl esters to VLDL/LDL
↓
Mediated by CETP
↓
VLDL/LDL carry CE to liver
Ultimately:
Liver excretes cholesterol as → Bile acids & bile salts
↓
Removal from the body
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