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BCH 3120 Lecture Notes - Peroxisome Proliferator-Activated Receptor, Carnitine Palmitoyltransferase Ii, Hypertriglyceridemia


Department
Biochemistry
Course Code
BCH 3120
Professor
Zemin Yao

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BCH3120Lipid/AminoAcidMetabolism2013
1
LipidandAminoAcidMetabolism
COURSENOTES
(Supplementarymaterialsfor
slidepresentations)
BCH3120/2013
ZeminYao
DepartmentofBiochemistry,MicrobiologyandImmunology
UniversityofOttawa
Email:zyao@uottawa.ca

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BCH3120Lipid/AminoAcidMetabolism2013
2
TableofContents
Introduction .................................................................................................................................... 3
1.FattyacidβoxidationandKetogenesis....................................................................................... 3
2.Fattyacidandtriacylglycerolsynthesis ........................................................................................ 9
3.Phospholipidsynthesis .............................................................................................................. 14
4.Biosynthesisofcholesterol ........................................................................................................ 20
5.Lipoproteinmetabolism ............................................................................................................ 26
6.Regulationofcholesterolhomeostasis...................................................................................... 33
7.Aminoaciddeaminationandtheureacycle .............................................................................. 40
8.Biosynthesisofaminoacidsandrelatedmolecules.................................................................... 46
9.Regulationofaminoacidmetabolism........................................................................................ 50

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BCH3120Lipid/AminoAcidMetabolism2013
3
LipidMetabolism‐Introduction
Theobjectiveofthenextsixlecturestitled“LipidMetabolism”isintendedtogivestudentsanoverviewon
theanabolism(i.e.synthesis)andcatabolism(i.e.degradation)ofthemostabundantlipidsinmammalian
cells.Specifically,studentsareexpectedtobecomefamiliarizedwithmetabolicpathwaysformajorlipid
classesandthesubcellularlocationsthateachpathwaytakesplace(i.e.compartmentalization).Inaddition,
studentsareexpectedtounderstandthebiologicalsignificancesoflipidmetabolicpathways,andto
appreciatetheintricaciesofregulatorymechanismsbywhichthehomeostasisofeachlipidclassis
achieved.
LipidMetabolism‐CourseOutline
Westartwiththefattyacidβoxidation,whichrepresentsoneofthemajormetabolicpathwaysin
mammalsforfuelgenerationandenergyutilization.Theβoxidationoccursinthemitochondria,andthe
biochemicalreactionsinvolvedintheprocesswereelucidatedbyearlywork.Morerecently,the
involvementofperoxisomesinβoxidationhasbeenrecognized.Clinically,drugsthatcanenhance
peroxisomalactionhavebeendevelopedtopromoteβoxidationoffattyacidsasaneffectivemeansto
fightagainstexcessiveaccumulationoffat(i.e.obesity)andrelatedmetabolicabnormalities.Thus,inthe
lectureof“FattyAcidβOxidation,”bothmitochondrialandperoxisomalpathwayswillbediscussed.In
addition,βoxidationofunsaturatedfattyacids,commonindiet,willalsobebrieflydescribed.
1.Fattyacidβoxidation
Structureandnomenclatureoffattyacids
Itiscommontoheartheterminologyof“saturated”and“unsaturated”fattyacids,whichdenotesthe
absenceorpresenceofdoublebondswithinafattyacidmolecule.Thenaturallyoccurringdoublebondsin
unsaturatedfattyacidsoftenassumecisconfigurationandrarelytransconfiguration.Transfattyacidsare
byproductsofhydrationofunsaturatedfattyacidsindairyindustry.
Conventionally,thepositionofdoublebondisindicatedbyΔfollowedwithnumeralsthatarecounted
beginningattheCOOHfunctionalgroup.Thus,18:1Δ9definesafattyacidmoleculeofan18carbonchain
withadoublebondatposition9(countedfromtheCOOHfunctiongroupdenotedas1).
Alternatively,thepositionofdoubleboundisindicatedbynumeralswithrespecttotheendthatisopposite
oftheCOOHfunctionalgroup.Inthiscase,theendofthefattyacidmoleculeisdenotedω(thelast
alphabetinGreek).Thus,18:1ω9describesafattyacidmoleculeofan18carbonchainwithadoublebond
atposition9withrespecttotheωend.Thisnomenclatureforfattyacidsisusuallyusedtodescribe
polyunsaturatedfattyacidsinwhichthedoublebondstartsatpositions3or6withrespecttotheωend.
Henceweheartheterminologyofω3andω6fattyacids.Forexample,EPA(eicosapentaenoicacid)is
commonlydenoted20:5(ω3)tospecifythemoleculeof20carbonchainwith5doublebondsstartingat
position3fromtheωend.
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