L10 lip transp Flashcards
LO2: expl how tiss obt lips req from lipop.
-chylom metab- chylom loaded in SI and apoB48 add. To lymph sys. Load TAG, ent lacteals, rnd LS to thoracic duct, nt L subclav vein. (See diag).
-LPL- hydrol TAG in lipop. Req apoCII cofactor. Att to surf of endoth cells. Rem score TAG from chylom and VLDL. Insulin incr its synth by tiss. Rels FA (to tiss) and glycerol (to liv).
-LCAT- rem core lip from lipop=unstable as surf:core lip incr. stab restore if LCAT conv surf to core- imp in form and maint lipop. Conds chol to CE using FA from phosphatid choline. Defic= unstable lipop, fail transp.
-VLDL, IDL, LDL metab- (see diag)
LDL no apoC/E so not effic cleared by liv as liv LDLR high affin apoE. LDL long liv= oxid dam, lip peroxidat. Oxidised LDL to Mac= foam cell accum= fatty streak= atheroscler plaques.
-familial hyper chol- absence (homoz) or defic (heteroz) func LDLRs= incr LDL and chol in plasma. Homoz atheroscler early, heteroz later.
-LDLR med endoc- LDLR PM of cells req chol. ApoB100 lig. R/LDL complex endoc to endo some. Fuse lysos=dig to chol and FA. LDLR exp contr by chol conc in cell.
-HDL metab- see diag.
New HDL by liv and int, low TAG. HDL budd off chylom and VLDL as dig by LPL. Free apoAI can also acq chol and Plip from other lipop and mems to form nascent like HDL.
Transf lip to HDL not req enz activ. HDL rem chol from cells with lot to liver or cels req more for metab/use. Imp for BV as decr foam cell and plaque.
ABCA1- prot in cell facil transf chol to HDL, then conv to CE by LCAT.
ATP bind cassette fam.
HDL can also exch CE for TAG with VLDL by chol exch transf prot CETP in plasma.
LO3: expl how distrurb to lip transp= clinic prob.
-hyperlipoproteinaemias- incr plasma lev lipop. Over prod or under rem. Detec- enz, R, apop.
6 main classes-
T1- cause- chylom in fasting plasma. NO link CAD. Defec LPL.
TIIa- assoc CAD, poss sev. Defec LDLR.
IIb- assoc CAD. Unkn defec.
III- incr LDL and chylom remn. Assoc CAD. Rare. Defec aopE.
IV- assoc CAD. Defec unkn.
V- incr chylom and HDL fast plasma. Assoc CAD. Unkn cause.
WHO sys classif based on plasma gluc conc, tot chol and TAG and plasma lipop elecphor. Diff tx’s.
-clinic signs- incr blood chol. Chol depos-
Xanthelasma yell patch eyelids. Tend xanthoma nodules. Corneal arc us- white circle rnd eye, Comm in eld norm.
-incr serum LDL assoc atheroscler. Mac eng LDL accum intima. Plaque rupt= thrombus clott and dam tiss.
-dyslipoproteinaemias- (ALL)
Any defec in metab plasma lipop prim inborn or sec acq due to diet/drugs/diab.
LO4: expl how hyperlipop Tx.
-init appr- diet decr chol and sat lip. Incr fib= interf abs bile salt= less abs so liver use more chol to make more. Lifestyle- incr exerc and stop smok to decr CVD risk.
-if no resp- drugs-
Statins- decr chol synth, inhib HMG-CoA reductase. Eg atorvastatin. Secondary eff incr LPL.
Bile salt sequestration- bind bile salt in GIT= liv use chol to make more eg colestipol. Some chol excret direc in bile.
-tot chol: HDL-C ratio over 6 is high risk. Tot chol should be under 5mM. TAG under 2mM fasted.
LO1: expl how lips transp in blood.
-lipids- TAG- diacylglycerol/ mono. FA. Chol-chol esters. Plip. ADEK.
Struc div. phob insol= prob blood transp. Bound to carriers. 2% lipids (FA most) bound to alb, lim capac 3mM. 98% carried as lipoprot partics=Plip, chol, CE, prots, TAG.
TAG 1mM, Plip 2.5, tot chol 5mM over= incr CVD. CE 3.5mM, FFA 0.4. TOT 4000-8500mg/l. High comm CAD.
-Plip- pol head Phillic= phosphatid choline or inisitol. Joined to glycerol to non pol phobic FA tails. Form liposome 2 mem, micelle 1. Bilay sheet.
-chol- some from diet, most synth in liv. Mem fluidity. Precurs ster horms- cortisol, aldost, testosterone, oestrogen. Precurs bile ac. Transp as CE= chol esterif with FA by lecithin chol acylt (LCAT) or acyl coA chol a/t.
-lipop- cont var amnts TAG, CE, ADEK, Plip in non cov assoc specif prots. Classif by- lip transported, lip ori and destin. Periph apolipop eg apoC/E. Integ apoA/B. Plip mono lay with some chol.
Apop= pack as phob regs interac lip and Phillic interac H2O. May inv in activ enz or recog cell surf Rs.
Surf= Plip, chol, apop. Phob core TAG and CE. Ratio core:surf lip=stab. So as circ lip upt by tiss-surf decr. Core only rem by eg lipase/transferase. Surf free.
-5 classes acc to density- blood levs clinic imp.
Chylomicron and VLDL main carriers of fat.
IDL (short liv, less imp), LDL, HDL- main carriers of CE.
Each var content of apolipop, TAG, chol, CE.
Dens obt by flotat centrif. Diam inv propor to dens.
Chylomicrons large diam small % prot so low dens. HDL small diam large % prot to high dens. Chylom norm only in blood 4-6 HR after meal. Creamy.
-each class lipop has assoc prots (apolipop)- 6 Maj classes ABCDEH.
Imp- apoB (VLDL, IDL, LDL). ApoAI (HDL). ApoB100. Integ or periph. 2 roles- STRUC pack water and insol lip, and FUNC cofactor and lig DS for surf Rs.
Diffs in what stor and apolipop= diff elec charge, size, weight, dens. Sep by elecphor/ultracentrifuge.
Chylom remn from rem TAG- rem lip from VLDL=IDL and LDL gen.
-funcs of plasma lipop-
Chylom- diet TAG int to tiss eg adip and ultim liv for metab.
VLDL- TAG liver to adip stor.
IDL- short liv precurs LDL. Chol liver to tiss.
LDL- chol liv to tiss.
HDL- excess tiss chol to liv dispos as bile salt and to cells req chol.
