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Ace Azcarraga

Cards (427)

  • Lipids

    Commonly referred to as fats and are composed mostly of carbon-hydrogen bonds
  • Major lipids in the body
    • Phospholipids
    • Cholesterol
    • Triglycerides
    • Fatty acids
    • Fat-soluble vitamins (A, D, E, K)
  • Lipids

    • They are the primary sources of fuel and provide stability to cell membranes and allow for transmembrane transport
    • They function as thermal insulators in subcutaneous tissues and around certain organs and precursors of other physiologically functional substances
    • They are insoluble in blood and water and they require special transport mechanisms (lipoproteins) for circulation in the blood
  • Phospholipid

    Most abundant lipid derived from phosphatidic acid
  • Forms of Phospholipids

    • Lecithin/ Phosphatidylcholine (70%)
    • Sphingomyelin (20%)
    • Cephalin (10%)
  • Phospholipids

    • They can form lipid bilayers and are a major component of all cell membranes
    • They participate in cellular metabolism and blood coagulation
    • They serve as a surfactant
  • Cholesterol

    1. hydroxy-5,6-cholestene, an unsaturated steroid alcohol containing four rings and a C-H side chain tail
  • Forms of Cholesterol

    • Free Cholesterol (30-40%)
    • Cholesterol Ester (60-70%)
  • Cholesterol

    • It can be converted in the liver to bile acids
    • It is essential for fat absorption in the intestines
    • It is a precursor substance of steroid hormones
    • It can be transformed to vitamin D3 after irradiation of skin to sunlight
    • It is used to evaluate the risk of atherosclerosis, myocardial and coronary arterial occlusions
    • It is used to monitor effectiveness of lifestyle changes and stress management
    • It is used as thyroid, liver and renal function tests; and for DM studies
  • Triglycerides

    Also known as Triacylglycerol (TAG), 3 fatty acids attached to glycerol by ester bonds
  • Triglycerides

    • When triglycerides are metabolized, their fatty acids are released to the cells and converted into energy, providing excellent insulation
    • Evaluates suspected atherosclerosis and measure the body's ability to metabolize fat
    • Fasting TAG ≥ 200 mg/dL are at risk for coronary artery disease
    • TAG and Cholesterol are the most important lipids in the management of coronary artery disease
  • Fatty Acids

    Linear chain of C-H bonds that terminates with a carboxyl group (-COOH), mainly derived from hydrolysis of triglycerides in adipose tissues
  • Forms of Fatty Acids
    • Esterified fatty acids
    • NEFA (Non-esterified fatty acids)
  • Classifications of Fatty Acids
    • According to length: Short chain (4 to 6 carbon atoms), Medium chain (8 to 12 carbon atoms), Long chain (>12 carbon atoms)
    • According to carbon double bond content: Saturated, Monounsaturated, Polyunsaturated
  • Cis fatty acids

    Both H atoms on the same side of the C=C double bond, more fluid compared to trans fatty acids
  • Trans fatty acids

    H atoms on opposite side of the C=C double bond, behave as saturated fatty acids
  • Fatty Acids

    • They are very important source of energy
    • They provide the substance for conversion to glucose (gluconeogenesis)
  • Lipoproteins

    Transport lipids (TAG and cholesterol) to sites of energy storage and utilization in the body, spherical, large macromolecular complex
  • Components of Lipoproteins

    • Lipids: Ampipathic lipids on surface (Cholesterol and phospholipids), Hydrophobic lipids in core (Triglycerides and cholesterol esters)
    • Proteins (apolipoproteins): Located on the surface, maintain structural integrity, act as ligands for cell receptors, activate/inhibit enzymes that modify lipoproteins
  • Apolipoproteins

    Keep the lipids in solution during circulation through the blood stream, interact with specific cell-surface receptors and direct lipids to the correct target organs and tissues in the body
  • Major Apolipoproteins

    • ApoA (major protein on HDL)
    • ApoB (major protein on VLDL, LDL & chylomicrons)
    • ApoC (major constituent of VLDL)
    • ApoD (minor apolipoprotein)
    • ApoE (found in VLDL, IDL, HDL, remnant lipoproteins & chylomicrons)
  • Major Lipoprotein Classes

    • Chylomicrons
    • Very Low Density Lipoprotein (VLDL)
    • Low Density Lipoprotein (LDL)
    • High Density Lipoprotein (HDL)
  • Chylomicrons

    • Largest lipoproteins, very rich in triglycerides of exogenous origin, produced by the intestines, deliver dietary lipids to hepatic & peripheral cells
  • VLDL

    • Wide range in size, major carrier of endogenous triglycerides, transfer triglycerides from the liver to peripheral tissues, increased production if there is excess dietary intake of carbohydrates, saturated & trans fatty acids
  • LDL

    • Formed from the lipolysis of VLDL, delivery of exogenous cholesterol to cells, comprises about 50% of human plasma lipoproteins, known as the "bad cholesterol" as it promotes atherosclerosis
  • HDL

    • Smallest, most dense lipoproteins, synthesized by both liver & intestines, known as the "good cholesterol" as they are antiatherogenic (remove excess cholesterol from peripheral cells and return it to the liver)
  • Minor lipoproteins

    LpA (composition similar to LDL but lesser in concentration), Intermediate-density lipoprotein (IDL) (formed as triglycerides are removed from VLDL)
  • Abnormal lipoproteins

    LpX (found in obstructive biliary disease, almost 90% lipids), beta-VLDL (faulty catabolism of VLDL, remnants derived from VLDL cannot be metabolized completely and accumulate in plasma)
  • Lipid Absorption Pathway

    1. Dietary lipids undergo intestinal digestion
    2. Lipids packaged into chylomicrons
    3. Chylomicrons enter the circulation & interact with proteoglycans on capillaries
    4. Chylomicrons carry triglycerides to tissues
    5. Chylomicron remnants rapidly taken up by liver
  • Endogenous Pathway

    1. Liver: Triglycerides are packaged into VLDL and secreted into circulation
    2. VLDL converted to IDL and LDL as triglycerides are removed
    3. LDL delivers cholesterol to cells
    4. HDL removes excess cholesterol from cells and returns it to liver
  • Lipid digestion and absorption
    1. Lipids undergo intestinal digestion
    2. Lipids packaged into Chylomicrons
    3. Chylomicrons enter the circulation & interact with proteoglycans on capillaries
    4. Proteoglycans promote binding of lipoprotein lipase that hydrolyzes TGL on chylomicrons
    5. Chylomicrons carry TGL to tissues
    6. Free fatty acids & glycerol from hydrolysis of TGL are taken by cells and used as source of energy
    7. Excess fatty acids reesterified into TGL by fat cells for long term storage
    8. During lipolysis there is transfer of lipid and apolipoproteins onto HDL, chylomicrons are converted into chylomicron remnant particles
    9. Chylomicron remnants rapidly taken up by liver
    10. Remnants broken down by enzymes to release FFA's, cholesterol and AA's
    11. Some cholesterol converted to bile acids
    12. Some cholesterol excreted (half reabsorbed in the intestines, remainder appears in stool)
  • Endogenous lipid transport pathway
    1. Liver: TGL are packaged into VLDL
    2. VLDL carries TGL to circulation
    3. In the circulation, VLDL undergo lypolysis by the action of lipoprotein lipase, so fatty acids can enter tissues (adipose cells, where they are re-esterified and stored as fat)
    4. Half of VLDL converted to LDL
    5. Remainder taken up as VLDL remnants by the liver
    6. VLDL converted to LDL
    7. LDL endocytosed by cells via LDL receptor
    8. TGL converted into NEFA & glycerol for energy
    9. Free cholesterol used for membrane biosynthesis
    10. Excess cholesterol converted to cholesterol ester by acyl-CoA:ACAT and stored in lipid drops
  • Reverse Cholesterol Transport pathway
    1. Excess cholesterol from cells is transported back to the liver by HDL
    2. Cholesterol diffuses out of cell and bind to HDL
    3. Cholesterol trapped in HDL after converted to cholesterol ester by LCAT (Lecithin-cholesterol acyltransferase)
    4. Cholesterol in HDL delivered to liver via SR-BI receptor
    5. About 50% of cholesterol on HDL transferred to LDL via CETP (cholesterol ester transfer protein)
    6. Cholesterol returned to liver via LDL receptor
    7. Cholesterol that reaches the liver are directly excreted into the bile or first converted to bile acid prior excretion
  • ABCA1 transporter pathway

    • Exact mechanism not known
    • Transporter transports lipid across the plasma membrane which is then removed by apoA-1 (HDL)
    • Defect in gene for ABCA1 transporter lead to Tangier disease
  • Hyperlipoproteinemia

    • Associated with elevated LPP levels
    • Elevated levels of cholesterol and TGL will also show elevated LPP levels since they are the transporter of these lipids
    • An isolated elevation of cholesterol can indicate that LDL is increased
    • Elevation of plasma TGL indicate that chylomicrons are significantly increased
    • Can be subdivided into hypercholesterolemia, hypertryglyceridemia and Combined Hyperlipidemia
  • Clinically significant hyperlipoproteinemia

    • Below 20 year old: 200 mg/dL cholesterol and 140 mg/dL TGL
    • Above 20 year old: 250 mg/dL cholesterol and 200 mg/dL TGL
  • Fredrickson-Levy Classification System of Hyperlipoproteinemias
    • Type I: Familial LPP lipase deficiency, Elevated chylomicrons (TGL)
    • Type IIa (Familial hypercholesterolemia): Deficiency of LDL receptors, Elevated LDL (cholesterol)
    • Type IIb (Familial hypercholesterolemia): Defective apoB, Elevated VLDL (TGL) & Elevated LDL (cholesterol)
    • Type III (Familial dysbetalipoproteinemia): Quantitative and qualitative defect in apoE, Elevated CM, LDL, IDL, Hyperlipidemia (Elevated TGL, cholesterol)
    • Type IV (Familial hypertriglyceridemia): Impaired VLDL catabolism, Elevated VLDL (TGL)
    • Type V (Mixed lipemia): Deficiency in apoC-11, an essential cofactor for lipoprotein lipase, VLDL hypersecretion, Elevated VLDL and chylomicrons (TGL), Cholesterol is also elevated
  • Hypercholesterolemia

    • Most closely linked to heart disease
    • Often associated with increased LDLc
    • LDL cholesterol builds up in circulation because there are no LDL receptors needed to transfer cholesterol into cells
  • Familial hypercholesterolemia

    • Homozygozous: 20-26 mmol/L cholesterol; first heart attack in teenage years
    • Heterozygous :8-15 mmol/L cholesterol
  • Hypertriglyceridemia

    • Generally a result of an imbalance between synthesis and clearance of VLDL in the circulation
    • Not directly implicated as risk for CHD (but many CHD patients have high TGL; TGL inversely proportional with HDL)
    • Can cause acute and recurrent pancreatitis
    • Genetic (Familial hypertriglyceridemia)