Lightbody Lecture 15 and 16 Flashcards Preview

Biochem Unit 2 > Lightbody Lecture 15 and 16 > Flashcards

Flashcards in Lightbody Lecture 15 and 16 Deck (49):

lipoprotein particles

Plipid, prot (apoprot), cholesterol (free and esterified), and TAG; transport lipids to periph tissues and return excess to liver; constant synth, transition, degrad, and removal from plasma; role in myo infarc, stroke, periph vasc disease, other inflam; synth in liver and intestine; heterogen in size and density; must go back to liver to be metab



90% TAG, 5% cholesterol, 2% prot (largest w/lowest density)



60% TAG, 20% chol, 5% prot; smaller and more dense than chylo



4% TAG, 50% chol, 25% prot; smaller and more dense than chylo or VLDL; Plipid single layer memb interspersed w/free chol (unesterified); apoprots are on surface (some integ, some periph); one apoB100 per LDL, encircles like belt; inner core is chol ester and TG



8% TAG, 30% chol, 33% prot; smallest and most dense



on lipoprot particle surface; interact w/receps on cells, det fate of LPP; activate/inhib enz's; each has unique set of apoprots; transferred from one LPP to another; diff isoforms (some assoc w/disease (AD-apoE)


Apo A-I

most abund prot on HDL; maturation of HDL and efflux of chol from cells to HDL; bds to scavenger receps on liver cells, activates LCAT (esterifies chol to FAs)


Apo B 100

req for form of VLDL; 1o prot of LDL, acts as ligand for LDL recep (LDLR) to allow chol deliv; v large (4400 AAs)


Apo B 48

truncated form of apo B 100, synth'd in intestine and req'd for chylomicron formation; only on chylos



on chylos, VLDL, HDL; activates lipoprotein lipase (LPL), exchanged b/w diff lipoprot classes



synth'd in liver and int, on chylos, VLDL, LDL, HDL; inv in inflam; high concs assoc w/cardiovasc disease


Apo E

synth in liver on HDL, trans to chylos and VLDL, where acts as ligand for rem chylo remnants and IDL from circul thru LDL recep or LRP recep (E2-4); may clear amyloid fr brain


Apo E4

genetic risk factor for late-onset AD; homozygote at 68y; hetero at 75; no alleles 84; E3 most common, but E4 have 20x risk of devel AD; E2 decreases risk



carry dietary TAG to other tissue to be used for E or stored; syn in enterocytes, sec into blood to LPL; resulting remnant endocytosed into liver, dig into individ cmpnts


lipoprotein lipase (LPL)

on capil walls of endothel cells; hydrol TAG to FFAs (80% - other 20% goes to liver); activated by ApoCII


intermed density lipoprot

formed in VLDL breakdown; 50% returns to liver, 50% becomes LDL (loses ApoE)


lipoprot lipase deficiency

evident in infancy; pancreatitis, nausea, musc pain, fatty deposits (xanthomas); elevated chol, high triglycerides after 12h fast, normal apo CII; restrict dietary fat (<10g/d); inc carbs and prots; inc fat-sol vits; mortality b/c pancreatitis


ApoE and Apo B 100 bdg

extended form on VLDL surface, can't bind w/recep; VLDL dec in size as TAG hydrol by LPL, /\ing conform of ApoE and B100 and allows them to bd to LDL recep as VLDL transformed to IDL


LDL fxn

derived from VLDL via IDL; has 4% TAG, 50% chol; main fxn is provide chol to periph tissue, return maj of excess to liver; 70% chol returned via LDL, rest via HDL; high assoc w/atherosclerosis, myo infarct, stroke, periph vasc disease (bad chol)


small, dense LDL

300x more likely to cause myo infarct or stroke; predictor of cardiovasc events and CAD



heterogeneous gp; synth in liver, some int; reservoir for CII and E; Apo A (combines w/scavenger recep on PM of liver instead of LDLR) is most abund prot on HDL surface; picks up free chol, esterifies it, transfers to LDL (70%) or VLDL or returns direc to liver (30% via HDL); at same t, VLDL and LDL transfer TAG to HDL; raised by exercise, low wt, no smoke, no trans fat, alcohol, omega FAs, niacin


ABCA1-ATP bdg cassette transporter

bds to apo-AI-->transport of free chol from cell to HDL, where esterified by LCAT


LCAT (lecithin-chol acyl transferase)

esterifies free chol to FAs; derived from PTC in HDL memb; activ by ApoA; not endocytosed into liver whole like LDL; puts chol in, then goes around again



glycoprot, transfers chol esters from HDL to LDL and VLDL and TAGs from LDL and VLDL to HDL; struc is long tunnel assoc w/HDL; genetic defect in this causes low heart disease; block this-->block chol transfer


CETP inhibitors

Torcetrapib; raised HDL a lot, lowered LDL a lot, lowered TG a little; 60% inc in mortality; now Anacetrapib, w/o these effects



small proinflam prot, on surface of chylos, VLDL, LDL, HDL; most abund apolipoprot in humans; high levels --> atherosclerosis and <3 disease; exact fxn unknown



high levels-->low inc of atherosclerosis; women have higher levels and less low levels and high inc of <3 dis


lipoprot receptors

memb receps; med internalization of lipoprot particle, allow cells to acquire chol and other lipids



7TM gene family; on PM of many cells (esp liver); bds to ApoB100 (on VLDL and LDL) and apo E (on chylos, VLDL, IDL); removes 70% of chol from circul; 839 AAs, 18 exons; 6 Cys that're disulfide bonded; epidermal GF domain; oligosaccharide domain; transmemb; cyto domain


scavenger receptors (SR)

bd to modified LDL (mLDL); also bd other anionic ligands; not subject to fdbk regulation like LDLR; on macs, dendritic cells, endothel cells


LDLR epidermal GF homology domain

30%; 3 EGF repeats; 2 and 3 are sep by propeller region (sep LDL from receptor)


cyto domain of LDLR

50 AAs; cont signal seq for internalization of receptor


LDLR path and chol reg in liver

LDLRs are neg chg'd clustered in pits on memb; after bdg of LDL, whole complex endocytosed; LDLR sep fr LDL, recycled back to memb surface; LDL degraded by lysosomes, releasing free chol


excess chol in liver reduced by

HMG CoA reductase syn., LDLR syn., HMG CoA reductase degrad (ubiquination), esterification (by ACAT-aCoA chol acyltransferase) and storage


familial hypercholesterolemia

autosomal dominant; mutations in LDLR gene-->high chol levels (600-800mg/dl), premature absence/dysfxn of LDLR (1/2 in heteros); homos have xanthomas



on macs, endothel, sm m; recep for mLDL but not LDL; imp role in foam cell generation; no fdbk ctrl, so macs cont to accum chol (foam cells)



glycoprot w/509AA; large extracell loop w/2 TM domains; 8 Cys; on macs, adipocytes, liver; bd to LDL, mLDL, HDL; ApoA on HDL is ligand to this, plays role in transfer of chol fr HDL to liver cells


SR-B deficiency

have high concs of chol, lg HDL particles



16mln w/attack/stroke; fueled by inflam imm response



below endothel layer; mainly CT; in healthy, few scattered macs, SM cells, LDL; inflam process occurs here (chol accum, atherosclerosis occurs); LDL particles accum here (LDL transcytoses through endothel layer)



= OxLDL; macs, endothel, SM cells secrete inflam cytokines; LDL mod initiates atherosclerosis (foamy macs-->coalesce-->plaque)


cap formation

atheroma is lipid pool w/foam cells, necrotic cells, free and esterified chol; cap forms on top w/macs, lymphocytes, and SMCs; SMCs sec collagen, elastin, proteoglycans to form fibrous matrix around cap


proteases from macs

thin the cap at edges, causing rupture and contents come into contact w/procoag elements in blood-->acute thrombus occluding the lumen; areas exp to blood are platelet adhes sites, sec cytokines that perpetuate process, inc potential for thrombus/clot


atheroma w/ or w/o plaque disruption

doesn't nec completely occlude lumen; proc can be repeated mult times; only 20% lumen blocked when rupture takes place to completely block artery, on avg


HDL removal of chol

chol can be remv'd from mac foam cells by transport via ACDA1 transporter to HDL (to liver for breakdown); req ApoA; reduces chol conc in plaques (sim to chol removal from periph cells by HDL)


LDL driven atheroma resulting in stenosis

usu results in angina, can be detected by stress test/angiogram before attack


LDL driven atheroma non-stentotic

not detected by angio/stress test; maj of plaque ruptures occur at areas w/o suff narrowing to be detected; worse b/c no pain, can't detect until attack


inc risk of inflam and athero

age, gender, smoking, obesity, T2DM, hypertension/ANG, menopause, high TAGs; other inflam dis like AD, psoriasis, asthma, arthritis, periodontal disease


biochem markers for inflam detection

C-reactive prot; synth in liver; 5 monomers of 25000 MW each; adipocytes and macs synth IL6 cytokine, which induces liver to synth CRP; rise in inflam response somewhere (not specific to type of disease); elevated in cardiovasc disease; drop in ppl who exercise, stop smoking, lose weight; plaques less likely to rupture when CRP low; can have bad effect w/low LDL if high CRP