Lipid

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• Define lipid
  • not polymer
  • small molecules
  • have strong tendency to associate thro noncovalent forces→ionic, H, Van der Waals, hydrophobic
• Functions
  • lipid signaling
  • provide better absorption for vitamin
  • provide efficient thermal insulator
  • serves to cushion organs against shock
  • energy storage
  • basic building blocks of bio/lipid membrane
• Simple lipids
  • FA
    • monocarboxylic acid with hydrocarbon chains
    • key components of lipid
    • metabolic fuels
    • oxidation of FA yields more energy than protein
    • C16 & C18→0~3 double bonds
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    • CnH2n+1COOH
    • butyric acid C3H7COOH in butter
    • most abundant saturated→palmitic acid CH3(CH2)14COOH 16:0
    • most abundant monoenoic→oleic acid CH3(CH2)7CH=CH(CH2)7COOH 18:1
    • human→PUFA with methylene interrupted double bonds of cis
    • major component of C18 PUFA
      • linoleic acid→cannot synthesized in human
      • linolenic acid in food
      • both precursor of C20 & C22
    • arachidonic acid
      • phospholipid
      • precursor of prostaglandin & eicosanoid
      • 4 double bond between c5-6, 8-9, 11-12, 14-15
      • 20:4(n-6)
    • prostaglandin
      • unsaturated of 20 carbons, 4 double bonds, 5-member ring
      • seminal fluid
      • smooth muscle
      • precursor→arachidonic acid PGA,B,D,E,F
      • aspirin inhibit biosynthesis of prostaglandin
    • nervonic acid, cis DHA→nervous system
    • gamma linolenic acid→EPO 18:3(n-6)
    • conjugated linoleic acid→9 cis 11 trans octadecadienoate
  • TAG
    • esterification of glycerol moiety with OH
    • derived from diet, de novo synthesis in liver, storage depots in adipocytes
    • neutral fats
    • may contain unsaturated (oil, liquid at room temp), saturated (fat, solid at room temp) or mixed
    • less oxidized than carb
    • release more energy
    • poor heat conductor, prevent heat loss
    • store energy more efficiently than glycogen→glycogen + H2O
    • adipocyte store TAG
    • major storage & transport FA
    • hydrophobic, coalesce into compact anhydrous droplets
    • insoluble in aqueous→bile salt synthesized in liver & stored in gallbladder
    • simple TAG
      • tristearin→3 residues of stearic acid
      • tripalmitin→animal fat, 3 residues of palmitic acid
      • triolein→olive oil, 3 oleic acid residues
    • mixed TAG
      • stearo-oleo-palmitin
      • glycerol + stearic acid, oleic acid, palmitic acid
  • DAG
    • 2 moles of FA per mole of glycerol
    • key cellular mssger
    • rarely present at greater than trace levels
    • intermediate in biosynthesis of TAG and other lipids
    • generated on hydrolysis of PI by phospholipase C
  • monoacylglycerol
    • one mole of FA per mole of glycerol
    • intermediate of enzymatic hydrolysis of TAG
    • positional isomer=powerful surfactant
  • wax
    • FA esterified to long chain alcohol
    • saturated/1 double bond
    • weak hydrophilic
    • water insoluble
    • energy storage, waterproof, self-cleaning (ear), eco location, water repellent, lubrication, protective coat, hair conditioning(sebum)
• Complex lipids
  • phospholipid
    • hydrophobic domain→hydrocarbon chains of FA
    • hydrophilic domain (polar head)→P
    • bilayer, amphipathic
    • emulsify agent
    • surface active agent
    • lowers surface tension of liquid to spread out over surface
    • types
      • phosphoglyceride
        • glycerol, FA, P, alcohol
        • cell membrane
        • glycerophospholipid→blood lipoprotein, bile, lung surfactant
        • source of PUFA→arachidonic acid
        • types
          • phosphatidic acid→glycerol 3 phosphate (polar) esterified with 2 FA (nonpolar)
          • PC PE neutral phospholipid
          • phosphatidylethanolamine 2nd most abundant
          • phosphatidylcholine→reservoir of membrane bound arachidonic acid for eicosanoid synthesis
          • PS PI acidic
          • phosphatidylserine protect brain cells
          • phosphatidyl inositol for signal transduction, anchor that tether protein to surface of PM
      • sphingolipid
        • sphingosine, FA, P, alcohol
        • abundant in CNS
        • IC comm
        • antigenic determinant of ABO
        • receptor by virus & bacterial toxin
        • form myelin sheath
        • signal transduction
        • structural bone→sphingosine, unbranched C18 alcohol with trans double bond between C4 & 5, amino at C2, OH at C1 & 3
        • basic unit
          • ceramide=N-acylsphingosine
          • long chain FA + amino of sphingosine
          • + PC = sphingomyelin
        • 4 class
          • sphingomyelin (P)
            • PC + C1 OH ceramide
            • myelin sheath→successive wrappings of cell membrane of specialized myelinating cells around nerve cell axon
            • facilitate rapid transmission of nerve impulse
          • cerebroside & ganglioside (glycosphingolipid)
            • saccharide head
            • glycosphingolipid
            • membrane of brain & nerve cells
            • cerebroside
              • 1 monosaccharide + beta glycosidic + C1 of ceramide
              • galactocerebroside abundant in nerve tissue
              • 15% of lipids of myelin sheath
            • ganglioside
              • more complex glycosphingolipid
              • oligosaccharide contain N-acetylneuraminic acid (blue) + ceramide
              • GM2→2nd monosialo/NeuNac residue
          • sulfatide
          • globoside
      • sphingolipid storage ds
        • hereditary deficiency of beta hexosaminidase A that degrade ganglioside G→Tay-Sachs=sphingolipidoses
        • cell swell & die
        • blind, muscle weakness, seizure, mental retardation
  • isoprenoid
    • 5C
    • terpene
      • plant essential oil
      • monoterpene→2 isoprene, geraniol in geranium oil
      • sesquiterpene→3 isoprene farnesene in cironella oil
      • diterpene→phytol
      • triterpene→squalene in shark liver oil & olive oil
      • tetraterpene→carotenoid (orange pigment)
      • polyterpene
      • mixed terpene→VE, ubiquinone, VK, cytokinis, plant hormone
    • steroid
      • complex derivative of triterpene
      • 4 fused rings
      • cholesterol
        • tetracyclic ring with double bond in one of the ring & 1 free OH
        • maintain membrane fluidity
        • esterified form
        • precursor of 5 class of steroid hormone
          • glucocorticoid
          • mineralcorticid
          • androgen
          • estrogen
          • progestin
        • serum albumin→nonspecific carrier for steroid hormone
      • plant sterol
        • cardiac glycoside
        • toxic
        • ouabain from Strophanthus gratus seed
        • digitalis from Digitalis purpurea→cardiac muscle contraction for congestive heart failure treatment
  • lipoprotein
    • protein covalently linked to lipid
    • plasma a
    • transport lipid molecules thro bloodstream
    • lipid soluble antioxidant→a-tocopherol, carotenoid
    • protein component of lipoprotein→apolipoprotein/apoprotein
    • spherical, hydrophobic & apolar aa form inner core, hydrophilic & polar head outside
    • classification
      • chylomicron
        • largest, most diameter
        • deliver TAG from intestine via lymph & blood to muscle & adipose
        • deliver cholesterol to liver
      • LDL
        • deliver cholesterol to nonhepatic cells
        • enter cell by endocytosis after fuse with receptor then fuse with lysosome
      • HDL most dense
      • familial hypercholesterolemia
        • lack LDL receptor
        • prevalence 1:100, male 45.5% female 54.5%
• Eicosanoid
  • precursor→arachidonic acid
  • regulatory molecule
  • local regulator
  • thromboxane A2
    • platelet aggregation, smooth muscle in arterial walls constrict
    • cause localized change in blood flow
    • mediate pain sensitivity, inflammation, swelling
  • aspirin prevent formation of eicosanoid
  • 4 class
    • prostaglandin
      • synthesized in prostate gland
      • unstable, metabolized rapidly to inactive products
      • no significant concentration in blood
      • stimulate smooth muscle contraction of uterus→blood flow, pain, inflammation, fever, wake-sleep cycle
    • thromboxane
      • synthesized from platelet
      • 6 member ring contains ester
      • blood clot & decrease blood flow towards clot
    • leukotriene
      • synthesized in leukocyte
      • 3 conjugated double bond
      • acts as strong biological signals
      • D4 cause smooth muscle contraction lines airway of lung
      • adverse effect→asthmatic attack
    • lipoxin
      • lipoxygenase
      • linear
      • many OH
      • cause anti inflammatory
      • production enhanced in response to aspirin
• RDS
  • deficiency in synthesis of lung surfactant
  • dipalmitylPC→palmatate esterified to C1 & 2
  • PG
  • apoprotein
  • cholesterol→reduce surface tension of fluid within alveoli preventing collapse
  • AT1
  • AT2
  • premature infant→estimation of fetal head by ultrasonography, monitor fetal arterial O2 saturation, determine [PC] & [sphingomyelin] in amniotic fluid
• Alzheimer→3 allelic form apo E
• Atherosclerosis
  • atheromas accumulate in arteries (plaque)
  • calcify & protrude into arterial lumens
  • disrupt vital organ functions→brain, heart lungs
  • O2 & nutrient deprivation
  • macrophage found within plaque
  • high LDL
  • VC VE antioxidant retard plaque
• Lipid signaling
  • activation of nuclear receptor
• Cell growth
  • sphingosine 1 phosphate→ceramide
  • potent mssger
  • regulate Ca mobilization, cell growth, apoptosis
  • DAG & PIP→Ca mediated activation of protein kinase C
• Inflammation
  • prostaglandin
  • arachidonic acid
  • estrogen, testosterone, cortisol
  • oxysterol 25-hydroxy-cholesterol→LXR agonist
  • fat soluble vitamin ADEK isoprene based lipid stored in liver & fatty tissue
• Membrane
  • highly polar head + 2 hydrocarbon tail
  • 3 class→glycerophospholipid, sphingolipid, glycosphingolipid
  • double tail yield cylindrical shape, easily packed in parallel
  • hydrocarbon tail has FA
    • unbranched 14-24 C chains connect by single bonds alone (saturated)/both single & double (unsaturated)
  • micelles→tail inside, COOH water
  • if mix with water & oily/greasy, micelle form oil droplet, emulsify
  • soap, synthetic detergent action
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• Lipid as energy reserve
  • complete metabolic oxidation of TAG→37kJ per g
  • carb & protein→17kJ per g
  • 70 kg human→400k kJ in total body fat & 100k kJ in total protein (muscle)
  • FA oxidation
  • brain unable to use FA
  • when starve & blood glucose low, brain use ketone bodies