Chapter 5 lipids metabolism

Outline 1. Classification of Lipids /FA and Nomenclature2. Digestion of Triglyceride3. Metabolism of TG4. Metabolism of phospholipids5. Metabolism of cholesterol6. Lipoproteins metabolism

LIPIDSWater-insoluble substances that can be extracted from cells by nonpolar organic solvents

Section 1 Classification and Functions of Lipids1. Triglyceride, TGVariable lipids: - As storage and transport form of metabolic fuel9 kcal/gram due to energy rich fatty acid chain - To keep the body temperature - Fats are solids; oils are liquids - To protect the visceras2. LipoidBasic lipidsCholesterols, Phospholipids, Glycolipids et al - As structural components of biological membranes - Cholesterol serves the precursor of bile salt and steroid hormones3. Lipid ramification: to involve the different functions

Triglyceride Triglyceridestriacylglycerols,called Neutral Fats - made of 3 free fatty acids and 1 glycerol - FA 4-22 Carbons long (mostly 16-20) - 95% of dietary lipids (fats & oils)

FAacids obtained by the hydrolysis of fats and oilsAccording to the number of carbon atom short chain(2~4C), medium chain (6~10C) and long chain(12~26C) fatty acidAccording to whether it contains double bond or not (saturate & unsaturate fatty acid)Systemic nomination ( catalogue, or n catalogue)Classification of FA and Nomenclature

Unsaturated FA and Essential FASaturated (have only single bonds)Unsaturated (have double bonds)Essential FA - the body cannot synthesize - must originate from dietary sources - polyunsaturated fatty acids linoleic:(18:2,9,12) linoleinic:(18:3, 9,12,15) arachidonic acid :(20:4, 5,8,11,14)

Omega-3 / Omega-6 Fatty AcidsSources of omega-3 fatty acid: soybean, salmonEicosapentaenoic acid( 20:5 -3, EPA): found in oils of shell fish, cold-water tuna, sardines, and sea mammalsDocosapentaenoic acid DPA 22:5 -3 Docosahexaenoic acid DHA22:6 -3 Sources of omega-6 fatty acidsVegetable oilsNuts and seeds

Section 2 Digestion and absorption of Triacylglycerols

6 Steps of Digestion and Absorption of lipids1. Minor digestion of triacylglycerols in mouth and stomach by lingual lipase and gastric lipase 2. Major digestion of all lipids in the lumen of the duodenum() and jejunum by Pancreatic lipases3. Bile acid facilitated formation of mixed micelles that present the lipolytic products to the mucosal surface, followed later by enterohepaticbile acid recycling

4. Passive absorption of the lipolytic products from the mixed micelle into the intestinal epithelial cell glycerol and FA 12 carbons in length are re-synthesized into TGs in theendoplasmic reticulum TGs then form large lipid globules in the ER called nascent chylomicrons. Severalapolipoproteins are required5. Re-esterification of 2-monoacylglycerol, lysolecithin, and cholesterol with free fatty acids inside the intestinal enterocyte 6. Assembly and export from intestinal cells to the lymphatics of chylomicrons coated with Apo B48 and containing triacylglycerols, cholesterol esters and phospholipidsAbsorption of lipids

Section 3 Metabolism of TGSynthesis of TGCatabolism of TGLipogenesis: Fatty Acid SynthesisSome poly-unsaturated FA ramification

1. The synthesis of TG1). Mono-acylglycerol pathway (MAG pathway)2). Diacylglycerol pathway (DAG pathway)

1). MAG pathway(dietary fat digestion and absorption in intestinal mucosal cell )

2). DAG pathway (for TG synthesis of in adipose tissue, liver and kidney) ATP ADP

Catabolism of TG involves two separate pathways1). Glycerol pathway2). Fatty acids pathway2. Catabolism of TG

The glycerol is absorbed by the liver and converted to glycolytic intermediates1). Glycerol pathway

2). Fatty acids pathway --- catabolism of FA Mobilization of triacylglycerolsFatty acid bata oxidationKetosis

Mobilization of triacylglycerolsin the adipose tissue, breaks down triacylglycerols to free fatty acids and glycerol (fatty acids are hydrolyzedinitially from C1or C3 of the fat)

Limiting enzyme triglyceride lipasehormone sensitive lipase HSL Hormone-sensitive lipase is the key enzyme responsible for the mobilization of free acids from adipose tissue, It is the rate limiting enzyme in the degradation of triacylglycerol to diacylglycerol and free fatty acids. Its hydrolyzing activity is under tight hormonal control lipolytic hormoneantilipolytic hormone (insulin)

** Fatty acid bata oxidation1. Evidence2. Steps in Beta Oxidation : - activation - transport - reaction process

1. evidenceEven carbon atoms C6H5-CH2-CH2-CH2-CH2-CH2-CH2-CH2-COOH C6H5-CH2-COOH (Phenylacetic Acid,) + Gly phenylacetylglycine () Franz Knoop 1904

Odd carbon atoms C6H5-CH2-CH2-CH2-CH2-CH2-CH2-COOH C6H5-COOH (Benzoic Acid,) + Gly

Hippuric acid () Franz Knoop 1904

2. Steps in Beta Oxidation1). Fatty Acid Activation by esterification with CoASH 2). Membrane Transport of Fatty Acyl CoA Esters 3). Carbon Backbone Reaction Sequence - Dehydrogenation (FAD)- Hydration- Dehydrogenation (NAD+)- Thiolase Reaction (Carbon-Carbon Cleavage)

1). Activation of Fatty AcidsAcyl CoA synthetase reaction occurs on the mitochondrial membrane

2). Transport into Mitochondrial MatrixCarnitine carries long-chain activated fatty acids into the mitochondrial matrix

Carnitine carries long-chain activated fatty acids into the mitochondrial matrix

3). Fatty acid Beta oxidationEach round in fatty acid degradation involves four reactions(1) oxidation to trans-2-Enoly-CoARemoves H atoms from the and carbons-Forms a trans C=C bond-Reduces FAD to FADH2 2-CoA

(2) Hydration to Lhydroxylacyl CoAAdds water across the trans C=C bondForms a hydroxyl group (-OH) on the carbonL(+)-CoA2--CoA

(3) Oxidation to Ketoacyl CoAOxidizes the hydroxyl groupForms a keto group on the carbon CoAL(+)-CoA

(4) Thiolysis to produce AcetylCoA acetyl CoA is cleaved:By splitting the bond between the and carbons.To form a shortened fatty acyl CoA that repeats steps 1 - 4 of -oxidationCoA -2CCoA + CoA

-Oxidation of Myristic(14 C) Acid

-Oxidation of Myristic (14 C) Acid7 Acetyl CoA6 cycles

Why call it bata oxidation

Cycles of -OxidationThe length of a fatty acidDetermines the number of oxidations and the total number of acetyl CoA groups Carbons in Acetyl CoA -Oxidation CyclesFatty Acid (C/2) (C/2 1)12 6 514 7 6168718 98

-Oxidation and ATPActivation of a fatty acid requires: 2 ATPOne cycle of oxidation of a fatty acid produces: 1 NADH 3/2.5 ATP 1 FADH2 2/1.5 ATPAcetyl CoA entering the citric acid cycle produces: 1 Acetyl CoA12/10 ATP

ATP for Myristic Acid14 CATP production for Myristic(14 carbons):Activation of lauric acid -2 ATP7 Acetyl CoA7 acetyl CoA 12/10 ATP/acetyl CoA 84/70 ATP6 Oxidation cycles 6 NADH 3/2.5ATP/NADH 18/15 ATP6 FADH2 2/1.5ATP/FADH2 12/ 9 ATP

Total 112/92 ATP

Oxidation of Special Cases (monounsaturated fatty acids)

Odd Carbon Fatty Acids5 Cycles5 CH3COSCoA + CH3CH2COSCoAPropionyl CoAD-MethylmalonylCoAL-MethylmalonylCoASuccinyl CoATCA CyclePropionyl CoA CarboxylaseATP/CO2EpimeraseMutase

Vit. B12

cell membraneFA = fatty acidLPL = lipoprotein lipaseFABP = fatty acid binding proteinCYTOPLASMCAPILLARY Overview of fatty acid degradation ACS = acyl CoA synthetase

3. Ketogenesis (Ketosis): formation of Ketone Bodies *****2 CH3COSCoA CH3COCH2COSCoAThiolaseCH3COSCoAAcetoacetyl CoAHO2C-CH2-C-CH2COSCoAOHCH3Hydroxy methylglutaryl CoA(HMG CoA)HMG CoASynthaseCholesterol(in cytosol)SeveralstepsKetogenesis(in liver: mitochon-drial matrix)

Ketogenesis: formation of Ketone BodiesHO2C-CH2-C-CH2COSCoAOHCH3HMG CoACH3COCH2CO2HAcetoacetic AcidHMG CoAlyase- CH3COSCoA- CO2CH3COCH3Acetone(volatile)CH3CHCH2CO2HOHHydroxybutyrateNADH + H+NAD+DehydrogenaseKetone bodies are important sources of energy, especially in starvation

Oxidation of ketone bodies in brain, muscle, kidney, and intestine

The significance of ketogenesis and ketogenolysisKetone bodies are water soluble, they are convenient to transport in blood, and readily taken up by non-hepatic tissues In the early stages of fasting, the use of ketone bodies by heart, skeletal muscle conserves glucose for support of central nervous system. With more prolonged starvation, brain can up take more ketone bodies to spare glucose consumption. High concentration of ketone bodies can induce ketonemia and ketonuria, and even ketosis and acidosis When carbohydrate catabolism is blocked by a disease of diabetes mellitus or defect of sugar source, the blood concentration of ketone bodies may increase,the patient may suffer from ketosis and acidosis

Overview Catabolism of TGTCATGFA

Lipogenesis: Fatty Acid SynthesisFatty acid are synthesized and degraded by different pathwaysIs the synthesis of fatty acids from acetyl CoA Synthesis takes place in the cytosolIntermediates are attached to the acyl carrier protein (ACP)The activated donor in the synthesis is malonylACPFatty acid reduction uses NADPH + H+Elongation stops at C16 (palmitic acid)

Citrate ShuttleAcetylCoA is synthesized in the mitochondrial matrix, whereas fatty acids are synthesized in the cytosolAcetylCoA units are shuttled out of the mitochondrial matrix as citrate:

Structure of Coenzyme AR = H; Coenzyme A

Reactivity of Coenzyme AAcetyl coenzyme A is a source of an acetyl group toward biological nucleophiles(it is an acetyl transfer agent)Nucleophilic acyl substitution+HSCoA

Reactivity of Coenzyme AAcetyl coenzyme A reacts with biological electrophiles at its carbon atomcan react via enolE+

Formation of Malonyl Coenzyme AFormation of malonylCoA is the committed step in fatty acid synthesis O || CH3CSCoA + HCO3- + ATP Acetyl CoA O O || || -OCCH2CSACP + ADP + PiMalonyl () CoA

Formation of Acetyl and Malonyl ACPThe intermediates(acetyl-ACP and malonyl-ACP) in fatty acid synthesis are covalently linked to the acyl carrier protein (ACP)

In bacteria the enzymes that are involved in elongation are separate proteinsIn higher organisms the activities all reside on the same polypeptide.To start an elongation cycle, AcetylCoA and MalonylCoA are each transferred to an acyl carrier protein O ||CH3CSACP ( Acetyl-ACP) O O || || -OCCH2CSACP (Malonyl-ACP)

Multifunctional Fatty Acid SynthaseDomain 1Substrate entry (AT & MT) and condensation unit (CE)Domain 2Reduction unit (DH, ER & KR)Domain 3Palmitaterelease unit (TE)

Fatty Acid Synthase Mechanism

Condensation and Reduction In reactions 1 and 2 of fatty acid synthesis:Condensation by a synthase combines acetyl-ACP with malonyl-ACP to form acetoacetyl-ACP (4C) and CO2 (reaction 1) Reduction converts a ketone to an alcohol using NADPH (reaction 2)

Dehydration and ReductionIn reactions 3 and 4 of fatty acid synthesis:Dehydration forms a trans double bond (reaction 3)Reduction converts the double bond to a single bond using NADPH (Reaction 4)

Lipogenesis Cycle Repeats Fatty acid synthesis continues:Malonyl-ACP combines with the four-carbon butyryl-ACP to form a six-carbon-ACP.The carbon chain lengthens by two carbons each cycle

Lipogenesis Cycle Completed Fatty acid synthesis is completed when palmitoyl ACP reacts with water to give palmitate (C16) and free ACP.

Summary of Lipogenesis

Elongation and UnsaturationEndoplasmic reticulum systems introduce double bonds into long chain acylCoA'sReaction combines both NADH and the acylCoA's to reduce O2 to H2Oconvert palmitoylCoA to other fatty acidsReactions occur on the cytosolic face of the endoplasmic reticulum.MalonylCoA is the donor in elongation reactions

Comparing -Oxidation and Fatty Acid Synthesis

Fatty Acid FormationShorter fatty acids undergo fewer cycles Longer fatty acids are produced from palmitate using special enzymesUnsaturated cis bonds are incorporated into a 10-carbon fatty acid that is elongated furtherWhen blood glucose is high, insulin stimulates glycolysis and pyruvate oxidation to obtain acetyl CoA to form fatty acids

Stoichiometry of FA synthesisThe stoichiometry of palmitate synthesis:Synythesis of palmitate from MalonylCoASynthesis of MalonylCoA from AcetylCoAOverall synthesis

Sources of NADPHThe malate dehydrogenase and NADP+linked malate enzyme reactions of the citrate shuttle exchange NADH for NADPH

Regulation of Fatty Acid SynthesisRegulation of Acetyl carboxylaseGlobal+ insulin- glucagon- epinephrineLocal+ Citrate- PalmitoylCoA- AMP

Eicosanoid HormonesEicosanoid horomones are synthesized from arachadonic acid (20:4).Prostaglandins20-carbon fatty acid containing 5-carbon ringProstacyclinsThromboxanesLeukotrienescontain three conjugated double bonds

Eicosanoid Hormones

Eicosanoid Hormones

Eicosanoid Hormones

Section 4Metabolism of phospholipids

PhospholipidsStructureGlycerol + 2 fatty acids + phosphate groupFunctionsComponent of cell membranesLipid transport as part of lipoproteinsFood sourcesEgg yolks, liver, soybeans, peanuts

PhospholipidsPhospholipids are intermediates in the biosynthesis of triacylglycerolsThe starting materials are L-glycerol 3-phosphate and the appropriate acyl coenzyme A molecules

Biosynthesis of glycerophospholipids1) DAG shuntDAG shunt is the major pathway for biosynthesis of phosphatidyl choline (lecithin) and phosphatidyl ethanolamine (cephalin). Serine is the source of choline and ethanolamine. CDP-choline and CDP-ethanolamine are the active forms of choline and ethanolamine respectively

CDP-DAG shuntPhosphatidic acidCDP-DAG shunt is the major pathway for the synthesis of phosphatidyl serine, phosphatidyl inositol and cardiolipin. In this pathway, DAG is activated as the form of CDP-DAG.

Degradation of glycerophospholipids

Metabolism of sphingolipidsSphingolipids are a class of lipids containing sphingosine instead of glycerol include: glycosphingolipids phosphosphingolipids N-The structure of phosphosphingolipidsThe structure of glycosphosphingolipidsR

Section 5Metabolism of cholesterol

Structure of CholesterolHOCH3HHHCH3CH3CH3CH3Fundamental framework of steroidsStructure of Cholesterol

Cholesterol Biosynthesis Formation of Mevalonate2 CH3COSCoA CH3COCH2COSCoAThiolaseCH3COSCoAAcetoacetyl CoAHO2C-CH2-C-CH2COSCoAOHCH3-Hydroxy-bata-methyl-glutaryl CoA (HMG CoA)HMG CoASynthaseHO2C-CH2-C-CH2CH2OHOHCH33R-Mevalonic acidHMGCoAreductaseCoASHKey control stepin cholesterolbiosynthesisLiver is primary site of cholesterol biosynthesis

Isoprenoid CondensationHeadTailHeadTailIsopentenylPyrophosphate (IPP)DimethylallylpyrophosphateHead to tailCondensationGeranyl Pyrophosphate (GPP)Farnesyl Pyrophosphate (FPP)Head to tailcondensationof IPP and GPPTail to tailcondensationof 2 FPPsSqualeneHeadTailHead

TailIsoprenes

Conversion of Squalene to CholesterolSqualeneSqualenemonooxygenase2,3-Oxidosqualene:lanosterol cyclaseLanosterol20 StepsCholesterolAcyl-CoA:cholesterolacyltransferaseCholesterol esters(principal transport form in blood)O2Squalene-2,3-epoxide

Cholesterol Biosynthesis: Processing of Mevalonate -O2C-CH2-C-CH2CH2OHOHCH3Mevalonate-O2C-CH2-C-CH2CH2OPOPCH3

OH2 StepsATP5-Pyrophospho-mevalonateCH2=C-CH2CH2OPOPCH3- CO2- H2OIsopentenylpyrophosphateCH3-C=CH2CH2OPOPCH3DimethylallylpyrophosphateIsomerase

Transformations of CholesterolCholesterol is the biosynthetic precursor to a large number of important steroids: Bile acids Vitamin D3 Corticosteroids Sex hormones

Section 6Lipoproteins metabolism

General Features of LipoproteinsApolipoproteins: specific lipid-binding proteins that attach to the surface intracellular recognition for exocytosis of the nascent particle after synthesisactivation of lipid-processing enzymes in the bloodstream, binding to cell surface receptors for endocytosis and clearance.

Main lipid components: triacylglycerols, cholesterol esters, phospholipids. Major lipoproteins: chylomicronsvery low density lipoproteins (VLDL)low density lipoproteins (LDL) high density lipoproteins (HDL)

Subfraction: intermediate density lipoproteins (IDL)

Electrophoretic mobility (charge):HDLs = lipoproteinsLDLs = -lipoproteinsVLDLs = pre- lipoproteins (intermediate between and mobility)Plasma lipoproteins

Model of low density lipoprotein. Other lipoproteins have a similar structure differing in the core content of lipid and the type of apoproteins on the surface of the molecule

composition of lipoproteins

LIVERApoB48 aids with chylo-micron assemblyLymph system:Chylomicrons to capillaries via lymphINTESTINEnon-hepatic tissuesExogenous pathway of lipid transport. Chylomicrons carry dietary fatty acids to tissues and the remnants take cholesterol to the liver

Chylomicron (or VLDL)Apo CIILIPOPROTEIN LIPASEPolysaccharideChainEndothelialSurface of cellTriacylglycerolin coreFree fatty acidsGlycerolTo LiverFree fatty acidsIn cellulo (muscle & adipose)CapillaryLipoprotein lipase action on chylomicron triacylglycerol (an identical reaction occurs with VLDL)

LIVERApoB48non-hepatic tissuesExogenous pathway of lipid transport. Chylomicrons carry dietary fatty acids to tissues and the remnants take cholesterol to the liver

LIVERHDL scavenge cholesterolThe liver-directed endogenous pathway of lipoprotein metabolismnon-hepatic tissuesLPL hydrolyze TAGs; FFA uptake; LDL circulate to tissuesapo B100 on LDL bind to receptorLDL taken into the cell to deliver cholesterol CII and E release to HDLApo E binds liver receptor Cholesterol uptake; excreted as bile acids

Nascent Chylomicron Assembly in Gut Mediated by B48Nascent HDL Assembled in liver Loans apo E/ apo CII to nascent chylomicronsMature Chylomicron Apo E and CII added from HDLLipoprotein Lipase capillary walls hydrolyzes TAG deliver FFA into adipose/muscleMature HDL CE from peripheral cells via LCAT activated by apo A1 Apo CII returned by chylomicrons

Chylomicron Remnant from mature chylomicron apo CII returned to HDLChylomicrons: Exogenous PathwayHDL: Both Pathways Chylomicron Processing and Interface with HDLMature Chylomicron Apo E and CII added from HDL CII activates LPL

Lipoprotein Lipase capillary walls hydrolyzes TAG deliver FFA into adipose/muscleLDL from mature VLDLNascent VLDL Assembly in Liver Mediated by B100VLDL/LDL: Endogenous PathwayHDL: Both Pathways VLDL/LDL Processing and Interface with HDLMature VLDL Apo E and CII added from HDLapo CII & E from HDLMature HDLApo CII/E returned by VLDL

Mature VLDL Apo E and CII added from HDL CII activates LPL

E ReceptorMature HDLCE MetabolismChylomicron Remnant E ReceptorB100receptorLDL Clearance of Cholesterol by Liver from Chylomicron Remnants, HDL and LDL

Oxidized LDL1. Uptake by "scavenger receptors" on macrophages that invade artery walls; become foam cells2. Elicits CE deposition in artery walls3. Atherosclerosis/CAD can developConsequence of Oxidized LDL FormationOxidation of LDLLDL

free pool ofcholesterol

LDLCEendocytosislate endosome ACEHCE cholesterolB100 amino acidsNPC-1 mediated transferCholesterol metabolism to bile acids or steroidsGolgi

MembraneCholesterol ACAT (stimulated by cholesterol)CECECE stored in dropletsCERPLCATMature HDL:Cleared by liveroooclathrin-coated pitooovesicleRecycling of receptortransport vesicle- lysosome fuse forming late endosome

sorting endosome: ligand/receptor dissociationlysosomeCellular cholesterol uptake, metabolism and releaseReverseCholesterolTransportRecycling of receptor and clathrin

Lipoprotein classes

Lipo-proteinSourceApo ProteinsProtein:Lipid/Major (minor) Lipid TransportedFunctionChylo-micronsgutB48, CII*, E*1:49triacylglycerol (CE)Dietary:FFA Adipose/muscleCE Liver via remnantsVLDLliverB100, CII*, E*1:9 triacylglycerol (CE)Synthesized:FFA adipose/muscleCE LDLLDLbloodB1001:3 cholesterol esterCE to liver (70%) and peripheral cells (30%)HDLliverA1, CII, E("ACE")1:1 cholesterol estersupplies apo CII, E to chylomicrons and VLDL; mediates reverse cholesterol transport

Functions of apolipoproteins & enzymes in lipid transport/processing

Protein (Enzyme)Site of ActionActivatorFunctionLPL (Enzyme)capillary wallsapo CIIexcises FFA from TAGs in chylomicrons and VLDLs for adipose and muscleACAT (Enzyme)inside cellsfree cholescholesterol ester storageLCAT (Enzyme)bloodapo A1cholesterol extraction from cells HDL carries CE for liver clearance (to bile acids)CERPplasma membraneapo A1 (choles.Induced)flips cholesterol (and lecithin) to outer layer of lipid bilayer for LCAT action in bloodTTPintestine/liversmooth ERnoneloads TAGs onto B48 (gut) and B100 (liver)Apo A1blood, plasma membranenoneactivates LCAT and CERP; binds to apo A1 receptors on cells requiring cholesterol extractionApo B48Gutnoneexport of chylomicrons from intestinal cellsApo B100Various cellsnoneligand for LDL receptor; export of liver VLDLApo CIIcapillary wallsnoneactivates lipoprotein lipaseApo Elivernonereceptor ligand - clears remnants, IDL, and HDL

mobilization of triacylglycerols:bata oxidationATP

1. ( )A (HSL)B C D E

2. ( )A B C ACTHD E

3. ,( )A B C D E

4. ( )A CoAB IC IID CoAE -

5. -( )A ,,,B ,,,C ,,, D ,,,E ,,,

6. ,( )A B C D E

7. ( )A B C D E

8. HMG-CoA( )A B C D E

9. ( )A BB VLDLLDLC LDLD HMG-CoAE (ACAT)

10. ( )A B CoAC D ATPE NADPH

11. The organ having the strongest ability of fatty acid synthesis is ( ) A fatty tissueB lacteal glandC liverD kidneyE brain

12. Which one transports cholesterol from outer to inner of liver? A CMB VLDLC LDLD HDLE IDL

13. Which one is essential fatty acid? A palmitic acidB stearic acidC oleinic acidD octadecadienoic acidE eicosanoic acid

14. The main metabolic outlet of body cholesterol is ( )A change into cholesterol esterB change into vitamine D3C change into bile acidD change into steroid hormoneE change into dihydrocholesterol

15. ( )A B C D E

16. ( )A B C D E

17. ( )A (HSL)B (LPL)C (HL)D (LCAT)E (ACAT)

18. ( )A B C D CM VLDLE LDL HDL

19. Which can be the source of acetyl CoA?A glucoseB fatty acidC ketone bodyD cholesterolE citric acid

20. The matters which join in synthesis of cholesterol directly are ( )A acetyl CoAB malonyl CoAC ATPD NADHE NADPH

- In this way, fats can be used as a source of material for glucose synthesis.- The reverse reaction is how glycerol is produced for the synthesis of fats.- These reactions occur near equilibrium. What drives the reaction is the subsequent hydrolysis of the pyrophosphate. We saw this before with the activation of glucose for glycogen synthesis.

- The pathway is called the -oxidation pathway.- Like succinyl dehydrogenase, this reaction uses FAD and is linked to Complex 2 of the electron transport chain.- The pathway is called the -oxidation pathway.- The hydration produces only the Lisomer.- The pathway is called the -oxidation pathway.- The pathway is called the -oxidation pathway.- The inner mitochondrial membrane is impermeable to Acetyl-CoA- The citrate lyase reaction requires an equivalent of ATP.- The shuttle allows Acetyl-CoA to be shuttled to the cytosol, where fatty acid synthesis can occur.- The shuttle consumes one equivalent of ATP.- The shuttle also substitutes an NADPH for an NADH, which is also needed for synthesis.

- This reaction is analogous to the pyruvate carboxylase reaction that we saw in gluconeogenesis. The coenzyme biotin used to activate the carbon dioxide.- The phosphopantetheine group is like the one found in Coenzyme A.- The ACP is small (77aa), and as whole, is like a large Coenzyme A.- The pantothenate arm of the ACP moves the intermdiates form one active site to the next.- Active sites from both subunits of the dimer participate.- Most of the NADPH for the the synthesis of palmitoyl-CoA still comes from the phosphate pentose pathway.- The AMP activated kinase is activated by AMP and inhibited by ATP- Glucagon and epinephrine activate protein kinase A, which inhibits the phosphatase by phosphorylating it- Insulin causes dephosporylation of Acetyl-CoA carboxylase by activating a phosphatase (do not know which one)- Prostaglanding influence cells locally by binding to 7TM receptors- Prostaglandins stimulate inflamation, regulate blood flow, control ion transport across membranes and modulate nerve transmission and induce sleep.- Aspirin blocks formation of prostaglandin H2- Prostaglanding influence cells locally by binding to 7TM receptors- Prostaglandins stimulate inflamation, regulate blood flow, control ion transport across membranes and modulate nerve transmission and induce sleep.- Aspirin blocks formation of prostaglandin H2- Prostaglanding influence cells locally by binding to 7TM receptors- Prostaglandins stimulate inflamation, regulate blood flow, control ion transport across membranes and modulate nerve transmission and induce sleep.- Aspirin blocks formation of prostaglandin H2- Prostaglanding influence cells locally by binding to 7TM receptors- Prostaglandins stimulate inflamation, regulate blood flow, control ion transport across membranes and modulate nerve transmission and induce sleep.- Aspirin blocks formation of prostaglandin H2