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17| Fa’y Acid Catabolism © 2013 W. H. Freeman and Company 21| Lipid Biosynthesis

Chapters 17,21 Fatty acid catabolism , Lipid biosynthesis

Jan 16, 2017



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  • 17| Fa'y Acid Catabolism

    2013 W. H. Freeman and Company

    21| Lipid Biosynthesis

  • Oxida=on of fa'y acids is a major energy source in many organisms

    About one-third of our energy needs comes from dietary triacylglycerols

    About 80% of energy needs of mammalian heart and liver are met by oxida

  • Fats provide efficient fuel storage

    The advantage of fats over polysaccharides: Fa=y acids carry more energy per carbon because they are more reduced

    Fa=y acids carry less water along because they are nonpolar (aggregate in lipid droplets and are unsolvated)

    Glucose and glycogen are for short-term energy needs, quick delivery

    Fats are for long-term (months) energy needs, good storage, slow delivery

  • Fat Storage in White Adipose Tissue



  • Dietary fa'y acids are absorbed in the vertebrate small intes=ne

    Emulsification by biological detergents (bile)

    Breakdown of TAG to DAG, MAG, FFA and glycerol

    Uptake by intestinal cells

    Chylomicrons (lipoproteins)

    Bloodstream to target tissues

    2nd breakdown of TAG

    Used for energy (muscles) or reesterified for energy (adipose)

    Remaining chylomicrons go to liver and enter by RME used for ketone bodies synthesis. When diet contains more f.a. than needed, liver converts them to TAG and packages them into VLDL to be transported to adipocytes

  • Lipids are transported in the blood as chylomicrons

    Apoliporpotein + lipids particles = lipoprotein Lipoproteins range in density: VLDL to VHDL

  • Hormones trigger mobiliza=on of stored triacylglycerols

    Hydrolysis of TAGs is catalyzed by lipases - can produce MAGs, DAGs, FFA and glycerol

    Some lipases are regulated by hormones glucagon and epinephrine Recall: Epinephrine means: We need energy now Glucagon means: We are out of glucose

  • Hormones trigger mobiliza=on of stored triacylglycerols

    Perilipins proteins that coat lipid droplets and restrict access to lipids to prevent premature mobiliza

  • Glycerol from fats enters glycolysis

    Only 5% of biologically-ac

  • Fa'y Acid Transport into Mitochondria

    Fats are degraded into fa=y acids and glycerol in the cytoplasm of adipocytes

    Fa=y acids are transported to other

  • Conversion of a fa'y acid to a fa'y acylCoA (1)

    Nucleophilic attack by f.a. anion

    Phosphoester linkage between f.a. carboxyl and phosphate of ATP

    Thioester linkage between f.a. carboxyl and thiol group of CoA-SH Hydrolysis of PPi to 2Pi is highly exergonic and pulls the first reaction forward

  • Acyl-Carni=ne/Carni=ne Transport



    Transesterification to carnitine

    Transesterification to CoA

    2 separate pools of CoA: Matrix CoA used mostly in oxidative degradation (pyr, f.a., a.a.) Cytosolic CoA used in biosynthesis of f.a.

    Carnitine-mediated entry is the rate limiting step for oxidation of f.a. in mito

  • Stages of Fa'y Acid Oxida=on

    Stage 1 consists of oxida

  • Stages of Fa'y Acid Oxida=on

  • The -Oxida=on Pathway Each pass removes one acetyl moiety in the form of acetyl-CoA.

    Palmitate (C16) undergoes seven passes through the oxidative sequence

    Formation of each acetyl-CoA requires removal of 4 H atoms {2 e pairs and 4 H+})

  • Step 1: Dehydrogena=on of Alkane to Alkene

    Catalyzed by isoforms of acyl- CoA dehydrogenase (AD) on the mitochondrial inner membrane Very-long-chain AD (VLCAD, 1218 carbons)

    Medium-chain AD (MCAD, 414 carbons)

    Short-chain AD (SCAD, 48 carbons) Results in trans double bond, different from naturally occurring

    unsaturated fa=y acids, between and C

    Analogous to succinate dehydrogenase reac

  • Step 2: Hydra=on of Alkene

    Catalyzed by two isoforms of enoyl-CoA hydratase: Soluble short-chain hydratase (crotonase) Membrane-bound long-chain hydratase, part of trifunc

  • Step 3: Dehydrogena=on of Alcohol

    Catalyzed by -hydroxyacyl-CoA dehydrogenase The enzyme uses NAD cofactor as the hydride acceptor Only L-isomers of hydroxyacyl CoA act as substrates Analogous to malate dehydrogenase reac

  • Step 4: Transfer of Fa'y Acid Chain

    Catalyzed by acyl-CoA acetyltransferase (thiolase) via covalent mechanism The carbonyl carbon in -ketoacyl-CoA is electrophilic Ac

  • Trifunc=onal Protein (TFP)

    Hetero-octamer Four subunits

    enoyl-CoA hydratase ac

  • Similar mechanisms introduce carbonyls in other metabolic pathways

  • Fa'y Acid Catabolism for Energy For palmi
  • NADH and FADH2 serve as sources of ATP

  • Oxida=on of Unsaturated Fa'y Acids Naturally occurring Unsaturated Fa=y acids contain cis double bonds Are NOT a substrate for enoyl-CoA hydratase

    Two addi

  • Oxida=on of Monounsaturated Fa'y Acids

    Oleate (18:1 9) converted to oleoyl-CoA and imported into mito via carnitine shuttle

  • Oxida=on of Polyunsaturated

    Fa'y Acids

    Linoleate (9,12)

  • First double bond requires isomeriza=on

  • Second requires reduc=on/isomeriza=on

  • Oxida=on of odd-numbered fa'y acids

    Most dietary fa=y acids are even-numbered Many plants and some marine organisms also synthesize odd-numbered fa=y acids

    Propionyl-CoA forms from -oxida

  • Carboxyla=on of Propionyl-CoA

  • Isomeriza=on to Succinyl-CoA CAC

  • Isomeriza=on in propionate oxida=on requires coenzyme B12

  • Complex Cobalt-Containing Compound: Coenzyme B12

    Very unstable bond Breaks to yield CH2

    . and Co3+ Used to transfer the hydrogen

    atom to a different C in the molecule (isomerization)

    No mixing of the transferred H atom with the hydrogen of the solvent (H2O)

    The formation of this complex cofactor occurs in one of two known reactions that cleaves a triphosphate from ATP

  • Regula=on of Fa'y Acid Synthesis and Breakdown


    Occurs only when need for energy requires it 2 pathways for f.a.CoA in liver: TAG synthesis in cytosol or f.a. oxida

  • Gene=c defects in fa'y acyl-CoA dehydrogenases

    Inability to oxidize fats for energy has serious effects on health

    More than 20 human gene

  • -Oxida=on in Mitochondria vs. Peroxisomes

    Differ in the first step: - passes es directly to O2 forming H2O2 which is quickly removed by the ac

  • oxida=on In the ER of liver and kidney For f.a. with 10 12 Cs Addi
  • Forma=on of Ketone Bodies

    Entry of acetyl-CoA into citric acid cycle requires oxaloacetate

    When oxaloacetate is depleted, acetyl-CoA is converted into ketone bodies (acetone, acetoacetate and D--hydroxybutyrate) Frees Coenzyme A for con

  • Release of Free Coenzyme A

    Another condensation with acetyl-CoA yields HMG-CoA

  • Forma=on of Ketone Bodies

    Cleaved into acetoacetate and acetyl-CoA

    Specific for the D-isomer; dont confuse it with L--hydroxyacyl-CoA DH of oxidation

    Untreated diabetes [acetoacetate] is high more acetone produced exhaled (odor)

  • Ketone Bodies as fuel In extrahepatic tissues: Ketone bodies can be used as fuels in all tissues except the liver The liver is a producer, not a consumer, of ketone bodies

    CAC Found in all tissues except the liver

  • Liver is the source of ketone bodies Produc
  • Lipids fulfill a variety of biological func=ons

    Energy storage Cons

  • Catabolism and anabolism of fa'y acids proceed via different pathways

    Catabolism of fa=y acids (excergonic and oxida=ve) produces acetyl-CoA produces reducing power (NADH and FADH2) ac

  • Subcellular localiza=on of lipid metabolism

  • Overview of Fa'y Acid Synthesis

    Fa=y acids are built in several passes, processing one acetate unit at a

  • Malonyl-CoA is formed from acetyl-CoA and bicarbonate

    The reac

  • The Acetyl-CoA Carboxylase (ACC) Reac=on Two-step rxn similar to carboxyla
  • Synthesis of fa'y acids is catalyzed by fa'y acid synthase (FAS)

    FAS system: Catalyzes a repea

  • FAS I vs. FAS II

    FAS I Single polypep

  • Fa'y Acid Synthesis Overall goal: a=ach two-C acetate unit from malonyl-CoA to a

    growing chain and then reduce it Reac

  • The General Four-Step Fa'y Acid Synthase I Reac=on in Mammals (1)

    Prep: Malonyl CoA and acetyl CoA (or longer fa=y acyl chain) are bound to FAS I

    - bind via thioester terminus of a Cys of the FAS - ac

  • Step 1 of FAS I: Elonga=on

  • Step 2: 1st Reduc
  • Steps 2-4 of the FAS I rxn

  • Overall Palmitate Synthesis

  • Acyl Carrier Protein (ACP) serves as a shu'le in fa'y acid synthesis

    Contains a covalently a=ached prosthe

  • Charging ACP and FAS I with acyl groups ac=vates them

    Two thiols must be charged with the correct acyl groups before condensa

  • Charging, Ac=va=on with ACP, and the Four-Step Sequence of Mammalian Fa'y

    Acid Synthesis

  • Ac
  • Carbonyl at C-3 is reduced to form D--hydroxybutyryl-ACP NADPH is e donor

    Catalyzed by -ketoacyl-ACP reductase (KR)

  • OH and H removed from C-2 and C-3 of -hydroxybutyryl-ACP to form trans-2-butenoyl-ACP

    Catalyzed by -hydroxyacyl-ACP dehydratase (DH)

  • NADPH is the electron donor to reduce double bond of trans-2-butenoyl-ACP to form butyryl-ACP

    Catalyzed by enoyl-ACP reductase (ER)

  • Enzymes in Fa'y Acid Synthase


  • The Transferase and FAS rxns are repeated in new rounds

    Product of first round is butyryl-ACP (bound to phosphopantetheine-SH group of ACP)

    Butyrul gp is transferred to the Cys of -ketoacyl-ACP synthase In the first round, acetyl-CoA was bound here

    New malonyl-CoA binds to ACP Aoer new round of four steps, six-C product is made (bound to ACP)

  • Beginning of the Second Round of Fa'y Acid Synthesis

  • Stoichiometry of Synthesis of Palmitate (16:0)

    1) 7 acetyl-CoAs are carboxylated to make 7 malonyl-CoAs using ATP

    7 AcCoA + 7 CO2 + 7 ATP 7 malCoA + 7 ADP + 7 Pi

    2) Seven cycles of condensa

  • Acetyl-CoA is transported into the cytosol for fa'y acid synthesis

    In nonphotosynthe

  • Fa'y acid synthesis occurs in cell compartments where NADPH levels are high

    Cytosol for animals, yeast Chloroplast for plants

    Sources of NADPH: In adipocytes: pentose phosphate pathway and malic enzyme

    NADPH is made as malate converts to pyruvate + CO2 In hepatocytes and mammary gland: pentose phosphate pathway NADPH is made as glucose-6-phosphate converts to ribulose 6-phosphate

    In plants: photosynthesis

  • Pathways for NADPH Produc=on

  • Acetyl-CoA, generated in the mitochondria, is shu'led to the cytosol as citrate

    In most eukaryotes, the acetyl-CoA for lipid synthesis is made in the mitochondria But lipid synthesis occurs in the cytosol

    And there is no way for acetyl-CoA to cross mitochondrial inner membrane to the cytosol

    So acetyl-CoA is converted to citrate Acetyl-CoA + oxaloacetate citrate

    Same rxn as occurs in CAC Catalyzed by citrate synthase Citrate passes through citrate transporter

  • Citrate is cleaved to regenerate acetyl-CoA

    Citrate (now in cytosol) is cleaved by citrate lyase Regenerates acetyl-CoA and oxaloacetate Rxn requires ATP Acetyl-CoA can now be used for lipid synthesis

    What happens to the oxaloacetate because there is no oxaloacetate transporter either?

  • Oxaloacetatecyt is converted to malate

    Malate dehydrogenase in cytosol reduces oxaloacetate to malate

    Two poten

  • Shu'le for Transfer of Acetyl Groups from Mitochondria to Cytosol

  • Fa'y acid synthesis is =ghtly regulated via ACC

    Acetyl CoA carboxylase (ACC) catalyzes the rate-limi

  • Importance of Citrate to Regula=on of Fa'y Acid Synthesis

    In animals, citrate s

  • ACC is also regulated by covalent modifica=on

    Inhibited when energy is needed Glucagon and epinephrine:

    reduce sensi

  • Regula=on of Fa'y Acid Synthesis in Vertebrates

  • Addi=onal Modes of Regula=on in Fa'y Acid Synthesis

    Changes in gene expression Example: Fa=y acids (and eicosanoids) bind to transcrip

  • Palmitate can be lengthened to longer-chain fa'y acids


  • Palmitate and stearate can be desaturated

    Palmitate(16:0)palmitoleate(16:1; 9) Stearate (18:0)oleate (18:1; 9)

    Catalyzed by fa=y acyl-CoA desaturase in animals Also known as the fa=y acid desaturases Requires NADPH; enzyme uses cytochrome b5 and cytochrome b5 reductase

    Note that this is a 9-desaturase! It reduces the bond between C-9 and C-10.

  • Vertebrate fa'y acyl desaturase is a non-heme, iron-containing, mixed func=on


    O2 accepts four electrons from two substrates Two electrons come from saturated fa=y acid Two electrons come from ferrous state of cytochrome


  • Desatura=on of a Fa'y Acid by Fa'y Acyl-CoA Desaturase

  • Plants can desaturate posi=ons beyond C-9

    Humans have 4, 5, 6, and 9 desaturases but cannot desaturate beyond 9

    Plants can produce: linoleate 18:2(9,12) -linolenate 18:3 (9,12,15)

    These fa=y acids are essen=al to humans Polyunsaturated fa=y acids (PUFAs) help control membrane fluidity

    PUFAs are precursors to eicosanoids Implica

  • Oxidases, Monooxygenases, and Dioxygenases

    Many enzymes use oxygen as an e acceptor, but not all of them incorporate oxygen into the product.

    Oxidases do not incorporate oxygen into the product Oxygen atoms usually end up in H2O2

    Oxygenases do incorporate oxygen into the product Monooxygenases incorporate one of the oxygen atoms into the product

    Dioxygenases incorporate both oxygen atoms into the product

  • Monooxygenases incorporate one oxygen into the product

    AH + BH2 + O-O A-OH + B + H2O Product is ooen hydroxylated, so also called hydroxylases or mixed-func=on oxygenases

    Example: Phenylanine hydroxylase hydroxylates phenylalanine to form tyrosine

    Deficiency causes phenylketonuria (PKU)

  • Cytochrome P450s are monooxygenases

    Important in drug metabolism Hydroxylate nonpolar molecules

    usually inac

  • Dioxygenases incorporate two oxygens in the product

    Usually metalloproteins Ac

  • Eicosanoids are potent short-range hormones made from arachidonate

    Eicosanoids are paracrine signaling molecules They include prostaglandins, leukotrienes, thromboxanes

    Created from arachidonic acid, 20:4 (5,8,11,14) Arachidonate is incorporated into the phospholipids of membranes

    In response to s

  • Prostaglandins are made by prostaglandin H2 synthase (cyclooxygenase, COX)

    COX (aka PGH2 synthase) is a bifunc

  • Conversion of Arachidonate to Prostaglandins and Other Eicosanoids

    Thromboxane synthase present in thrombocytes converts PGH2 to thromboxane A2

    Induce the constric

  • PGH2 synthase has two isoforms

    COX-1 catalyzes synthesis of prostaglandins that regulate gastric mucin secreEon

    COX-2 catalyzes synthesis of prostaglandins that mediate pain, inflammaEon, and fever

  • NSAIDs inhibit cyclooxygenase ac=vity

    Aspirin (Acetylsalicylate) is an irreversible inhibitor Acetylates a Ser in the ac

  • A Few NSAIDs that Inhibit PGH2

    Arachidonate (substrate)

    Advil, motrin Aleve

  • COX-2-specific inhibitors have a checkered history

    Developed to inhibit prostaglandin forma

  • Leukotriene synthesis also begins with arachidonate

    O2 is added to arachidonate via lipoxygenases Creates species that differ in the posi

  • Biosynthesis of Triacylglycerols Synthesized or ingested fa=y acids are either stored for energy or used in membranes depending on the needs of the organism

    Animals and plants store fat for fuel

    Plants: in seeds, nuts Typical 70-kg human has ~15 kg fat

    Enough to last 12 wks Compare with 12 hrs worth glycogen in liver and muscle

    Animals and plants and bacteria make phospholipids for cell membranes

  • The precursor for the backbone of fat and phospholipids is glycerol 3-phosphate

    Both pathways start by the forma

  • Acyl transferases a'ach two fa'y acids to glycerol 3-phosphate


  • To make TAG, phospha=dic acid is dephosphorylated and acylated


  • Conversion of Phospha=dic Acid into Triacylglycerol

  • Regula=on of Triacylglycerol Synthesis by Insulin

    Insulin results in s

  • Regula=on of Fat Metabolism by Glucagon and Epinephrine

    Glucagon and epinephrine result in s

  • Triacylglycerol breakdown and re-synthesis create a fu=le cycle

    Seventy-five percent of free fa=y acids (FFA) released by lipolysis are reesterified to form TAGs rather than be used for fuel Some recycling occurs in adipose

  • The Triacylglycerol Cycle * In mammals, TAG molecules are broken down and resynthesized in a TAG cycle even during starva
  • Benefits of this fu=le cycle?

    Recycling con

  • What is the source of the glycerol 3-phosphate needed for fa'y acid


    During lipolysis (s

  • Glyceroneogenesis makes DHAP for glycerol 3-phosphate genera=on

    Glyceroneogenesis contains some of the same steps of gluconeogenesis Converts pyruvate DHAP Basically, a shortened version of gluconeogenesis in the liver and adipose

  • Glyceroneogenesis

  • Regula=on of PEPCK expression is =ssue-dependent


  • Regula=on of Glyceroneogenesis via Glucocor=coid Hormones

  • Cor=sol and glucagon can elevate blood sugar

    1) PEPCK expression in liver gluconeogenesis (so [glucose])

    2) PEPCK expression in adipose

  • Thiazolidinedione drugs target insulin resistance by increasing glyceroneogenesis

    Elevated FFA levels seem to promote insulin resistance

    Thiazolidinediones upregulate PEPCK in adipose

  • Thiazolidinediones/Glitazones

    Have this group in common

    Avandia (Rosiglitazone) removed from market due to associa

  • Regula=on of Glyceroneogenesis via Thiazolidinediones

  • Biosynthesis of Membrane Phospholipds

    Begin with phospha

  • Further Details on A'aching the Head Group

    Either one of the alcohols is ac

  • Synthesis of Phospha=dylethanolamine and Phospha=dylcholine in Yeast


  • Phospholipid Synthesis in Mammals Phospha7dylserine isnt synthesized from CDP-diacylglycerol as it is in yeast and bacteria

    Made backwards from PE or PC via head group exchange rxns Catalyzed by specific synthases Pathway salvages the choline

  • Sphingolipids are made in four steps

    1) Synthesis of sphinganine from palmitoyl-CoA and serine

    2) A=achment of fa'y acid via amide linkage 3) Desatura=on of N-acylsphinganine

    (dihydroceramide) Yields N-acylsphingosine (ceramide)

    4) A=achment of head group Can yield a cerebroside or ganglioside



  • Phospholipids must be transported from the ER to membranes

    Phospholipids are: synthesized in the smooth ER transported to Golgi complex for addi

  • Four Steps of Cholesterol Synthesis

    1) Three acetates condense to form 5-C mevalonate

    2) Mevalonate converts to phosphorylated 5-C isoprene

    3) Six isoprenes polymerize to form the 30-C linear squalene

    4) Squalene cyclizes to form the four rings that are modified to produce cholesterol

  • Step 1: Forma=on of Mevalonate from Acetyl-CoA

    2 Acetyl-CoAs Acetoacetyl-CoA Catalyzed by acetyl-CoA acyl transferase


    Acetyl-CoA + Acetoacetyl-CoA -hydroxyl--methylglutaryl-CoA (HMG-CoA) Catalyzed by HMG-CoA synthase

    NOT the mitochondrial HMG-CoA synthase used in ketone body forma

  • Sta=n drugs inhibit HMG-CoA reductase to lower cholesterol


  • Step 2: Conversion of Mevalonate to Two Ac=vated Isoprenes

    3 PO43 transferred stepwise from ATP to mevalonate


  • Step 3: Six Ac=vated Isoprene Units Condense to Form Squalene

    The two isoprenes join head -to-tail, displacing one set of diphosphates forms10-C geranyl


    Geranyl pyrophosphate joins to another isopentenyl pyrophosphate forms 15-C farnesyl


    Two farnesyl pyrophosphates join head-to-head to form phosphate-free squalene

  • Step 4: Conversion of Squalene to Four-Ring Steroid Nucleus

    Squalene monooxygenase adds one oxygen to the end of the squalene chain forms squalene 2,3-epoxide

    Here pathways diverse in animal cells vs. plant cells

    The cycliza

  • Conversion of Squalene to Cholesterol

  • Fates of Cholesterol Aner Synthesis

    In vertebrates, most cholesterol synthesized in the liver, then exported: - As bile acids, biliary cholesterol or cholesteryl esters


  • Bile Acids Assist in Emulsifica=on of Fats

    Bile is stored in the gall bladder, secreted into small intes

  • Cholsteryl esters are more nonpolar than cholesterol

    Contain a fa=y acid esterified to the oxygen Comes from a fa=y acyl-CoA Makes the cholesterol more hydrophobic, unable to enter membranes

    Transported in lipoproteins to other

  • Cholesterol and other lipids are carried on lipoprotein par=cles

    Lipids are carried through plasma on spherical par

  • Four Major Classes of Lipoprotein Par=cles

    Named based on posi

  • Electron Microscope Pictures of Lipoproteins

  • Apolipoproteins in Lipoproteins

    Apo for without So apolipoprotein refers to the protein part of a lipoprotein par

  • Chylomicrons carry fa'y acids to =ssues

    Have more TAG and less protein hence, least dense.

    Have ApoB-48, ApoE, and ApoC-II

    ApoC-II ac

  • Chylomicron remnants deposit their cholesterol in the liver

    When chylomicrons are depleted of their TAG, remnants go to liver

    ApoE receptors in liver bind the remnants, take them up by endocytosis

    Remnants release their cholesterol in the liver

  • VLDLs transport endogenous lipids

    Cholesteryl esters and TAGs from excess FA and cholesterol are packed into very low-density lipoproteins (VLDL)

    Excess carbohydrate in the diet can also be made into TAG in the liver and packed into VLDL

    Contain apoB-100, apoC-I, apoC-II, apoC-III, and apoE

  • VLDLs take TAGs to adipose =ssue and muscle

    Again, ApoC-II ac

  • VLDL remnants become LDL

    Removal of TAG from VLDL produces LDL Because TAG removed, LDL is enriched in cholesterol/chloesteryl esters

    ApoB-100 is the major apolipoprotein

  • LDLs carry cholesterol from liver to muscle and adipose =ssue

    Muscle and adipose

  • Cholesterol Uptake by Receptor-Mediated Endocytosis

  • Familial hypercholesterolemia is associated with LDL receptor muta=ons


  • HDL carries out reverse cholesterol transport

    HDLs contain a lot of protein Including ApoA-I and lecithin-cholesterol acyl transferase (LCAT) Catalyzes the forma

  • Five Modes of Regula=on of Cholesterol Synthesis and Transport

    1) Covalent modifica

  • Regula=on of Cholesterol Metabolism

  • HMG-CoA reductase is most ac=ve when dephosphorylated

    1) AMP-dependent protein kinase - when AMP rises, kinase phosphorylates the enzyme ac

  • Longer-term Regula=on of HMG-CoA Reductase through Transcrip=onal Control

    Sterol regulatory element-binding proteins (SREBPs) When sterol levels are high, SREBP is in ER membrane with other proteins

    When sterol levels decline, complex is cleaved, moves to the nucleus

    SREBP ac

  • Regula=on of Cholesterol Synthesis by SREBP

  • Regula=on of HMG-CoA Reductase by Proteoly=c Degrada=on

    Insig (insulin-induced gene protein) senses cholesterol levels. Binds to HMG-Co-A reductase, Triggers ubiquina

  • Cardiovascular disease (CVD) is mul=-factorial

    Very high LDL-cholesterol levels tend to correlate with atherosclerosis Although many heart a=ack vic

  • How Plaques Form

    LDL with partly oxidized fa=y acyl groups s

  • How Plaques Form (cont.)

    Foam cells undergo apoptosis Remnants accumulate, along with scar

  • Familial Hypercholesterolemia

    Due to gene

  • Reverse cholesterol transport by HDL explains why HDL is cardioprotec=ve

    HDL picks up cholesterol from non-liver

  • Reverse Cholesterol Transport

  • Ques=on 7 (Take home exam) Due: NEXT WEEK (

    Please solve ques=ons: 1. 6 (uncouplers) 2. 17 (ATP turnover) 3. 22 (alanine) 4. 24 (diabetes) For wri[en answers, I prefer to have them typed in Word. I can accept the assignment in one file sent to my email. For answers that require solving mathemaEcally, you can either type them or write them down and scan them.