🧬 COMPLETE LECTURE: Biochemistry - Metabolism (Pages 89-92)

PAGE 89 - METABOLIC FUEL USE & FASTING/STARVATION

📊 The Energy Values Box (Top Right)

"1g carb/protein = 4 kcal | 1g alcohol = 7 kcal | 1g fatty acid = 9 kcal (#letters = #kcal)"

• Carbohydrate (sugar/starch) = 4 kcal per gram. "Carb" has 4 letters → 4 kcal. Simple memory trick!
• Protein (meat, eggs, dal) = also 4 kcal per gram. "Protein" has 7 letters... but the book says to use the trick for "prot" = 4. The actual value is 4 kcal.
• Alcohol = 7 kcal per gram. "Alcohol" has 7 letters → 7 kcal.
• Fatty acid (fat) = 9 kcal per gram. "Fatty acid" - the first word "fatty" has... the trick here is fatty acid = 9. Fat is the richest fuel. That's why eating fatty foods makes you gain weight easily - the same weight of fat has more than double the energy of carbs!

📈 The Graph - "Metabolic Fuel Use During Exercise"

1. Stored ATP (peaks at 0-2 seconds, then drops):
   • ATP = Adenosine Triphosphate. Think of ATP as ready-to-use cash in your wallet. Your muscles store a tiny bit of ATP directly.
   • At the very start of exercise (sprinting, explosive movement), you use this stored ATP immediately.
   • Why does it drop? Because you only have enough stored ATP for 1-2 seconds of maximal effort. Like your wallet - it runs out fast!
2. Creatine phosphate (peaks around 5-10 seconds, then drops):
   • Creatine phosphate is like a emergency backup power bank. When ATP runs out in 2 seconds, creatine phosphate instantly donates its phosphate to regenerate ATP.
   • Key point: This system needs NO oxygen (anaerobic). It's fast!
   • Why it drops: You only have enough creatine phosphate for about 10 seconds of maximal effort. This is why a 100-meter sprint can be fueled this way, but a 400-meter run cannot.
   • Clinical note: This is why athletes take creatine supplements - to increase this reserve.
3. Anaerobic metabolism (peaks around 30 seconds - 1 minute, then drops):
   • "Anaerobic" = without oxygen. This is glycolysis (breaking down glucose) that produces energy WITHOUT needing oxygen.
   • The byproduct is lactic acid (lactate). When you feel the burning sensation in your muscles during intense exercise - that's lactic acid building up!
   • Why it drops: Lactic acid builds up and causes fatigue. Also, this system is less efficient.
4. Aerobic metabolism (slowly rises, peaks around 2 minutes, stays sustained):
   • "Aerobic" = with oxygen. This is the most efficient system - like a powerful, fuel-efficient car engine.
   • Uses glucose, then fat, in the presence of oxygen to make lots of ATP.
   • Why it takes time to peak: Your heart, lungs, and blood vessels need time to deliver more oxygen to muscles.
   • Key point: For endurance exercise (running, cycling for hours), aerobic metabolism dominates.
5. Overall performance (gradual decline over 2 hours):
   • As all fuel sources start depleting and fatigue sets in, overall performance declines.
   • This is why marathon runners "hit the wall" - their glycogen stores deplete, and the body shifts to fat, which is slower to burn.

🍽️ FASTING AND STARVATION TABLE

"Priorities are to supply sufficient glucose to the brain and RBCs and to preserve protein."

• Brain: Your brain ONLY runs on glucose (under normal conditions). It cannot use fat directly. It's like a generator that only accepts one type of fuel. The brain needs a constant, uninterrupted supply of glucose or it malfunctions (confusion, coma, death).
• RBCs (Red Blood Cells): These cells have NO mitochondria (we'll explain this later). Mitochondria are the oxygen-burning energy factories. Without them, RBCs can ONLY use glucose. If glucose falls too low, RBCs can't function → can't carry oxygen → death.
• Preserve protein: Protein = your muscles, organs, enzymes. Breaking down protein means destroying your body. The body tries to avoid this as long as possible.

🥗 State 1: Fed State (After Meals)

"Glycolysis and aerobic respiration."

• After eating, blood glucose rises. Insulin (the "store it" hormone) is released.
• Glycolysis = breaking down glucose to make energy. Think of it as burning the glucose you just ate.
• Aerobic respiration = the full efficient pathway using oxygen to extract maximum energy.

"Insulin stimulates triglyceride (lipid) and glycogen (carbohydrate) storage alongside protein synthesis."

• Insulin = think of it as the "save and invest" hormone. When you eat a big meal, insulin says: "We have more energy than we need right now - let's save it!"
  • Triglycerides (TG) = fat stored in your fat cells (adipose tissue). Like putting money in a savings account.
  • Glycogen = glucose stored in chains, mainly in the liver and muscles. Like keeping some cash in a short-term account.
  • Protein synthesis = building new proteins/muscles. Insulin promotes muscle building.

🕐 State 2: Fasting (Between Meals)

"Hepatic glycogenolysis (major); hepatic gluconeogenesis, adipose release of FFA (minor)."

• Hepatic glycogenolysis = "Hepatic" means liver. "Glyco" = glycogen. "Lysis" = breaking down. So: The liver breaks down its stored glycogen back into glucose and releases it into the blood. This is the MAJOR way the body maintains blood sugar between meals. Like breaking open your short-term cash account.
• Hepatic gluconeogenesis = "Gluco" = glucose, "neo" = new, "genesis" = creation. So: The liver creates brand new glucose from non-sugar sources (like amino acids from protein, glycerol from fat). This is MINOR between meals because liver glycogen is still available.
• Adipose release of FFA = "Adipose" = fat tissue. "FFA" = Free Fatty Acids = fat broken down and released into the blood. Muscles begin using this fat for energy so they don't steal glucose from the brain.

"Glucagon and epinephrine stimulate use of fuel reserves."

• Glucagon = the opposite hormone to insulin. Released when blood sugar FALLS. It says "release stored energy!" It stimulates glycogen breakdown in the liver.
• Epinephrine (adrenaline) = the "fight or flight" hormone. Also mobilizes energy reserves. It's why you get a surge of energy when you're scared or excited.

⏰ State 3: Starvation Days 1-3

"Blood glucose levels maintained by:"

1. "Hepatic glycogenolysis"

   • Liver glycogen stores are still being used, but they are running out. Liver can only store ~100g of glycogen (enough for ~12-18 hours).

2. "Adipose release of FFA"

   • Fat cells (adipose tissue) ramp up release of fatty acids into the blood. Muscles switch to burning fat, sparing glucose for the brain.

3. "Muscle and liver, which shift fuel use from glucose to FFA"

   • The muscles and liver STOP using glucose as their primary fuel and switch to fat (FFA = Free Fatty Acids). This is critical - by doing so, they donate their share of glucose to the brain.

4. "Hepatic gluconeogenesis from peripheral tissue lactate and alanine, and from adipose tissue glycerol and propionyl-CoA (from odd-chain FFA - the only triacylglycerol component that contributes to gluconeogenesis)"

   Let me break this down:
   • Peripheral tissue lactate: When muscles work hard, they produce lactate (lactic acid). This travels to the liver, which converts it back to glucose. This cycle is called the Cori cycle - like a recycling program!
   • Alanine: An amino acid from muscle protein breakdown. The liver converts it to glucose. This is why starvation causes some muscle loss.
   • Glycerol from adipose tissue: When fat (triglycerides) are broken down, the "backbone" (glycerol) is released. The liver can convert glycerol to glucose.
   • Propionyl-CoA from odd-chain FFA: This is advanced - most fatty acids have an EVEN number of carbons and cannot become glucose. But RARE "odd-chain" fatty acids produce propionyl-CoA, which CAN enter gluconeogenesis. This is the ONLY fat component that can technically make glucose. Important for exams!

"Glycogen reserves depleted after day 1."

• By the end of day 1 without food, liver glycogen is GONE. The body now relies entirely on gluconeogenesis and fat burning.

"RBCs lack mitochondria and therefore cannot use ketone bodies."

• Mitochondria = the "powerhouse of the cell" - the organelles where oxygen-based energy production happens.
• Red blood cells have NO mitochondria (to make room for hemoglobin, the oxygen-carrying molecule).
• Ketone bodies = alternative fuel made from fat, which the brain can use during starvation. But using ketones requires mitochondria!
• So RBCs are permanently dependent on glucose only. The body MUST always maintain some glucose production just to keep RBCs alive.

💀 State 4: Starvation After Day 3

"Adipose stores (ketone bodies become the main source of energy for the brain). After these are depleted, vital protein degradation accelerates, leading to organ failure and death."

• Ketone bodies: After day 3, the brain - which normally only uses glucose - starts adapting to use ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone). These are made by the liver from fat.
• Think of it as the brain finally accepting an alternative fuel when its preferred fuel (glucose) is critically low.
• Ketone bodies are made from fat breakdown → fat cells are being depleted.

"Amount of excess stores determines survival time."

• A person with more body fat can survive starvation longer. An obese person has months of fat stores; a malnourished thin person may only survive weeks.

• Carbohydrate (lowest line, drops to zero by day 1): Glycogen stores - tiny and depleted almost immediately.
• Fat (middle line, very slowly declining over 8+ weeks): The main fuel reserve. The body carefully uses fat over weeks/months.
• Protein (top line, slowly declining): Muscle and organ protein - used as a last resort. When this drops significantly → organ failure and death.

PAGE 90 - LIPID TRANSPORT

🚢 What is Lipid Transport? (The Big Picture)

Step 1: Dietary Fat → Intestine → Lymphatics

"Dietary fat and cholesterol → Micelles → Lipids → Intestinal cell → Chylomicron → enters lymphatics (Step 1)"

• When you eat a fatty meal, fat arrives in your small intestine.
• Micelles: Bile salts (made by the liver, stored in gallbladder) wrap around fat droplets to form micelles - like soap breaking up a grease stain. This makes fat absorbable.
• Intestinal cells absorb the fat and package it into chylomicrons (the biggest lipoprotein - like a massive cargo ship).
• Chylomicrons are too big to enter blood vessels directly, so they enter the lymph system first (the thoracic duct).
• The lymph system eventually drains into the subclavian vein in the chest → enters the bloodstream.

"① Chylomicron enters lymphatics" The chylomicron, freshly made in the intestinal cell, goes into lymph vessels, NOT directly into blood.

"② HDL transfers apo CII and apoE"

• HDL = High-Density Lipoprotein = the "good cholesterol" carrier.
• Apo CII and ApoE = these are proteins sitting on the surface of HDL. Think of them as "loading dock workers" that HDL generously transfers to the chylomicron.
• Why does the chylomicron need these?
  • ApoE = the address label - tells the liver to take up the remnant later.
  • ApoC-II = the KEY that activates an enzyme called lipoprotein lipase (LPL). Without ApoC-II, LPL won't work!

"③ Chylomicron apo CII activates LPL (impaired in Type I familial dyslipidemia)"

• LPL (Lipoprotein Lipase) = an enzyme sitting on the walls of capillaries (tiny blood vessels) in muscle and fat tissue. Think of it as a scissors or a fuel pump.
• When a chylomicron floats past, ApoC-II on its surface activates LPL.
• LPL cuts the triglycerides (TG) out of the chylomicron and delivers the fatty acids to the underlying cells (muscle uses it for energy; fat tissue stores it).
• The chylomicron shrinks as its TG cargo is delivered, becoming a chylomicron remnant (still has cholesterol inside).

"Impaired in Type I familial dyslipidemia": If LPL or ApoC-II is defective (genetic condition), chylomicrons pile up in the blood → hypertriglyceridemia → pancreatitis.

"④ Liver releases VLDL (overproduction in Type IV familial dyslipidemia)"

• VLDL = Very Low Density Lipoprotein. Made by the liver. It carries triglycerides (TG) made by the liver to peripheral tissues (muscles, fat cells).
• Think of VLDL as the liver's delivery truck for fat.
• It also carries ApoB-100 on its surface (important - this is the "liver ID badge").
• Type IV dyslipidemia: The liver overproduces VLDL → too much TG in blood.

"⑤ VLDL apo CII activates LPL"

• Just like chylomicrons, VLDL also carries ApoC-II (donated by HDL).
• ApoC-II on VLDL activates LPL in capillaries → LPL strips TG from VLDL and delivers fatty acids to cells.
• As VLDL loses its TG, it becomes IDL (Intermediate Density Lipoprotein) and then LDL (Low Density Lipoprotein).

"⑥ IDL delivers TGs and cholesterol to the liver via apoE"

• IDL = the in-between stage. It's VLDL that's lost most of its TG but still has cholesterol.
• ApoE on IDL acts as the "address label" for the liver. The liver sees ApoE → grabs IDL via its ApoE receptor → IDL is taken up by the liver.
• Alternatively, IDL is further processed by hepatic lipase in the liver → becomes LDL.

"⑦ Endocytosis of LDL (impaired in Type II familial dyslipidemia)"

• LDL = the final product. It's mostly cholesterol now. It travels to ALL body cells.
• Cells have LDL receptors on their surface. LDL's ApoB-100 binds the LDL receptor → cell pulls LDL inside (endocytosis - literally "eating into the cell").
• Inside the cell, cholesterol is released and used for cell membrane construction, steroid hormone synthesis, etc.
• Type II familial hypercholesterolemia: LDL receptors are absent or defective → LDL can't be taken up → LDL piles up in blood → atherosclerosis (clogged arteries).

🎯 The Adipocyte (Fat Cell) Role

PAGE 91 - KEY ENZYMES IN LIPID TRANSPORT + APOLIPOPROTEINS

🔑 Key Enzymes in Lipid Transport

"Mediates transfer of cholesteryl esters to other lipoprotein particles."

• Cholesteryl esters = cholesterol molecules that have a fatty acid attached to them (esterified = chemically modified form of cholesterol for storage inside lipoproteins).
• CETP acts like a trading agent that moves cholesterol esters from HDL to VLDL, IDL, and LDL in exchange for TGs.
• This is important for HDL maturation (how HDL becomes a mature, functional particle).

"Degrades TGs remaining in IDL and chylomicron remnants."

• This enzyme sits on liver cells. After IDL docks at the liver, hepatic lipase strips off any remaining TG → IDL becomes LDL.
• Also processes chylomicron remnants.

"Degrades TGs stored in adipocytes. Promotes gluconeogenesis by releasing glycerol."

• This is the enzyme inside fat cells that is activated by hormones like epinephrine (adrenaline) and glucagon during fasting/exercise.
• When activated, HSL breaks down stored fat (TG) into FFA + glycerol.
• FFA → released into blood → fuel for muscles, liver.
• Glycerol → goes to the liver → used for gluconeogenesis (making glucose). That's why fat breakdown indirectly helps maintain blood sugar!
• Insulin INHIBITS HSL (when fed, you store fat, not break it down).

"Catalyzes esterification of 2/3 of plasma cholesterol (ie, required for HDL maturation)."

• Lecithin = a phospholipid (a type of fat).
• Esterification = chemically attaching a fatty acid to cholesterol to create a cholesteryl ester (a more compact, storable form).
• LCAT does this reaction on HDL: it takes free cholesterol picked up from cells and esterifies it, turning nascent HDL (baby HDL) into mature HDL (the actual "good cholesterol").
• Look at the diagram: Nascent HDL + ApoC-II + ApoE → activated by LCAT → Chol E (cholesterol ester) accumulates → Mature HDL.
• Then CETP transfers cholesterol esters from mature HDL to VLDL/LDL/IDL.
• Without LCAT, HDL cannot mature → can't do reverse cholesterol transport → cholesterol builds up in cells.

"Degrades TGs in circulating chylomicrons and VLDL."

• Already explained above. The enzyme on capillary walls that strips TG from chylomicrons and VLDL, delivering fatty acids to tissues.
• Activated by ApoC-II; inhibited by ApoC-III.
• Insulin stimulates LPL in fat tissue (after eating, store fat!).

"Degrades dietary TGs in small intestine."

• This enzyme is secreted by the pancreas into the small intestine.
• It breaks down dietary fat (TG from food) into FFA + monoglycerides so the intestine can absorb them.
• This is the initial step before chylomicron formation.
• Orlistat (a weight-loss drug) works by blocking pancreatic lipase → less dietary fat absorbed.

"Degrades LDL receptor → ↑ serum LDL. Inhibition → ↑ LDL receptor recycling → ↓ serum LDL."

• PCSK9 = Proprotein Convertase Subtilisin/Kexin Type 9 (don't memorize the full name, just understand the function).
• Think of PCSK9 as a "receptor destroyer". When LDL binds to the LDL receptor and gets taken into the cell, the receptor is normally recycled back to the cell surface to pick up more LDL.
• But PCSK9 intercepts this recycling - it destroys the LDL receptor, so fewer LDL receptors are available → less LDL is removed from blood → LDL stays high.
• PCSK9 inhibitors (drugs like evolocumab, alirocumab) are now used to treat high LDL cholesterol. By blocking PCSK9, receptors are recycled more → more LDL cleared from blood → lower LDL levels. These are very powerful cholesterol-lowering drugs!

📋 Major Apolipoproteins Table

1. Structural proteins (hold the particle together)
2. Address labels (tell receptors which lipoprotein to take up)
3. Enzyme activators/inhibitors (turn on or off enzymes like LPL and LCAT)

• ApoB-48: Made from the same gene as ApoB-100, but only 48% of the full protein is made (due to mRNA editing in the intestine). Found only on chylomicrons = "intestinal origin."
• ApoB-100: The liver makes the full (100%) protein. Found on VLDL → IDL → LDL. "I hope I LIVE to Be 100" = LIVER → B100. Brilliant memory trick!

PAGE 92 - LIPOPROTEIN FUNCTIONS + DISEASES

Lipoprotein Functions (Summary)

"Lipoproteins are composed of varying proportions of proteins, cholesterol, TGs, and phospholipids."

"LDL and HDL carry the most cholesterol."

• LDL carries cholesterol FROM the liver TO the tissues (and into artery walls if too much)
• HDL carries cholesterol FROM the tissues BACK to the liver for disposal

"Cholesterol is needed to maintain cell membrane integrity and synthesize bile acids, steroids, vitamin D."

• Keeps cell membranes fluid and functional (like oil in a machine)
• Is the starting material for all steroid hormones (testosterone, estrogen, cortisol)
• Makes bile acids (needed for fat digestion)
• Is the precursor for Vitamin D synthesis

Each Lipoprotein:

"Delivers dietary TGs to peripheral tissues. Delivers cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their TGs. Secreted by intestinal epithelial cells."

• Biggest, lightest lipoprotein. Made in intestine after eating fat.
• Delivers food fat to muscles and fat cells (via LPL).
• Delivers remaining cholesterol to liver as "remnants."

"Delivers hepatic TGs to peripheral tissue. Secreted by liver."

• Made in the liver. Delivers liver-made fat to the rest of the body.
• Think of it as the "liver's fat delivery service."
• VLDL → IDL → LDL (as it loses TG)

"Delivers TGs and cholesterol to liver. Formed from degradation of VLDL."

• The halfway point between VLDL and LDL.
• Half is taken up by the liver (via ApoE receptor); the other half is converted to LDL by hepatic lipase.

"Delivers hepatic cholesterol to peripheral tissues. Formed by hepatic lipase modification of IDL in the liver and peripheral tissue. Taken up by target cells via receptor-mediated endocytosis. Lethal."

• LDL is the main cholesterol delivery vehicle.
• When LDL is too high, it deposits cholesterol in artery walls → atherosclerosis (plaques) → heart attacks, strokes.
• That's why the book says "Lethal" - high LDL is one of the biggest cardiovascular risk factors!

"Mediates reverse cholesterol transport from peripheral tissues to liver. Acts as a repository for apo CII and apoE (which are needed for chylomicron and VLDL metabolism). Secreted from both liver and intestine. Alcohol ↑ synthesis. HDL is Healthy."

• HDL is the garbage truck of lipid transport - picks up excess cholesterol from artery walls and peripheral tissues and returns it to the liver for disposal.
• Reverse cholesterol transport = moving cholesterol BACKWARDS (tissues → liver, instead of liver → tissues).
• HDL also DONATES ApoC-II and ApoE to chylomicrons and VLDL (remember Step 2 in the lipid transport diagram).
• Alcohol increases HDL - this is one reason moderate alcohol was historically thought to be "cardioprotective" (though current guidelines don't recommend alcohol for this purpose).
• "HDL is Healthy" = high HDL is protective against heart disease.

Abetalipoproteinemia

"Autosomal recessive. Mutation in gene that encodes microsomal transfer protein (MTP). Chylomicrons, VLDL, LDL absent. Deficiency in apo B₄₈ and apo B₁₀₀-containing lipoproteins."

• Autosomal recessive = you need to inherit a defective gene from BOTH parents to get this disease.
• MTP (Microsomal Transfer Protein) = this is the machine inside intestinal and liver cells that packages fat into chylomicrons and VLDL. Without MTP, the packaging machine breaks → no chylomicrons, no VLDL, no LDL can be made.
• Result: Fat and fat-soluble vitamins (A, D, E, K) CANNOT be absorbed or transported. They pile up in intestinal cells.

"Affected infants present with severe fat malabsorption, steatorrhea, failure to thrive."

• Steatorrhea = fatty stools. The fat that can't be absorbed comes out in the stool. It looks greasy, pale, foul-smelling, and floats.
• Failure to thrive = the infant doesn't grow or gain weight properly because they can't absorb calories from fat.

"Later manifestations include retinitis pigmentosa, spinocerebellar degeneration due to vitamin E deficiency, progressive ataxia, acanthocytosis."

• Vitamin E deficiency because fat-soluble vitamins can't be transported without lipoproteins.
• Retinitis pigmentosa = progressive destruction of the retina → blindness.
• Spinocerebellar degeneration = damage to the spinal cord and cerebellum (balance center of the brain).
• Ataxia = inability to coordinate movements, unsteady walking.
• Acanthocytosis = red blood cells develop spiky projections ("acanthocytes" or "spur cells") due to abnormal fat composition of their membranes.
• Intestinal biopsy shows fat-laden enterocytes (intestinal cells stuffed with fat they can't export).

"Treatment: restriction of long-chain fatty acids, large doses of oral vitamin E."

• Avoid large amounts of regular fat (long-chain fats are the problematic ones).
• Give medium-chain triglycerides (MCT) as fat source - these can be absorbed directly into the portal blood without needing chylomicrons!
• Supplement Vitamin E aggressively to prevent neurological damage.

Familial Dyslipidemias Table

• Inheritance: AR (Autosomal Recessive) = both parents must carry the gene
• Pathogenesis: Lipoprotein lipase (LPL) deficiency OR ApoC-II deficiency. Without LPL or its activator (ApoC-II), chylomicrons CANNOT be processed.
• Elevated: Chylomicrons, TG, cholesterol
• Clinical:
  • Pancreatitis = inflammation of the pancreas. TG > 1000 mg/dL can cause severe pancreatitis (very dangerous, potentially fatal!).
  • Hepatosplenomegaly = enlarged liver and spleen (swollen with fat-laden macrophages).
  • Eruptive/pruritic xanthomas = crops of small, itchy, yellow-red bumps on skin = fat deposits under the skin.
  • Creamy layer in supernatant = if you take a blood sample and let it sit, a creamy white layer floats to the top (chylomicrons are so fat-rich they literally float!).
  • No ↑ risk for atherosclerosis = interestingly, chylomicrons are too big to enter artery walls, so despite massive hyperlipidemia, these patients don't get heart attacks from this alone.

• Inheritance: AD (Autosomal Dominant) = you only need ONE copy of the defective gene (more common than Type I)
• Pathogenesis: Absent or defective LDL receptors, OR defective ApoB-100 (the LDL receptor's "key"). Without the receptor or the key, LDL cannot be taken up by cells → LDL accumulates in blood.
• Type IIa: Elevated LDL + cholesterol only
• Type IIb: Elevated LDL + cholesterol + VLDL (more severe)
• Clinical:
  • Heterozygotes (1:500 people) = one good copy of LDL receptor gene + one bad. Cholesterol ~300 mg/dL (normal is <200). Manageable with statins.
  • Homozygotes (very rare) = both copies defective. Cholesterol ≥700 mg/dL. Catastrophic!
  • Accelerated atherosclerosis: These patients get heart attacks before age 20 (homozygotes may get MI in childhood!).
  • Tendon (Achilles) xanthomas = cholesterol deposits in the Achilles tendon at the back of the heel. Pathognomonic (highly characteristic) of familial hypercholesterolemia.
  • Corneal arcus = a grey-white ring around the cornea of the eye (cholesterol deposits). When seen in young people (<40 years), it suggests hypercholesterolemia.

• Inheritance: AR
• Pathogenesis: ApoE is defective (specifically type thrEE - the E4 isoform doesn't work as the address label). Without functional ApoE, chylomicron remnants and IDL cannot be taken up by the liver → they accumulate.
• Memory trick: Type thrEE = ApoE defect!
• Elevated: Chylomicrons, VLDL, TG
• Clinical: Premature atherosclerosis, tuberoeruptive and palmar xanthomas (yellow deposits in the skin creases of the palms are characteristic of this type!).

• Inheritance: AD
• Pathogenesis: The liver overproduces VLDL. Too much fat is packaged and exported by the liver.
• Elevated: VLDL, TG
• Clinical:
  • Hypertriglyceridemia >1000 mg/dL can cause acute pancreatitis (very similar to Type I clinically).
  • Related to insulin resistance = commonly seen in people with Type 2 diabetes, obesity, metabolic syndrome. Insulin normally suppresses VLDL production; when insulin doesn't work well (insulin resistance), the liver makes too much VLDL.

🎓 QUICK SUMMARY CHEAT SHEET