Lightbody Lecture 13 Flashcards
(38 cards)
cholesterol
most abund sterol; essential for membs; precursor of bile salts, steroids, vit D; all cells can synth, but main are liver, ad cortex, testes, ovaries; 2% of body mass; 30% in brain; brian must synth its own b/c can’t x BBB; exc as free chol or bile salts; synth in cyto and ER under circ rhythm (mas 6h after dark, min 6h after sunrise)
cholesterol v sitosterol
both have 27C, one OH gp, 1 db, mostly esterified; sito is plant sterol; reduce chol levels in humans b/c bd recep but not absorbed (prevent absorp) - only diff is extra ethyl gp on C24
HMG-CoA reductase
ctrling enz in chol biosynth; - by statins; rate limiting; reg dir and indir by diff kinds of metab ctrl (HMG-CoA to mevalonate)
7-a-hydroxylase
rate limiting rxn in bile acid and bile salt synth; bile salts feed back and inhibit here
chol biosynth req
18 mol acetyl-CoA, 36 ATP, 16 NADPH; 30 rxns
activated isoprene
precursor of many other metabolites; >20,000 isoprenoids; rubber, phytol chain of chlorophyll, Q, vit K, vit A, vit E, cholesterol, etc.
squalene synth
2 x farnesyl pyrophosphate + squalene synthase–>squalene (30C); or isopentenyl-PP + dimethylallyl-PP –> squalene
mixed fxn oxygenases
incorp oxy atoms directly into subst
dioxygenases
incorp both oxy atoms into substrate
monooxygenases
incorp only one atom into substrate; mixd fxn b/c oxidize 2 substrates simult
oxidase
uses O2 as e- acceptor, but no oxy incorp into substrate! don’t confuse w/oxygenases…
lanosterol
from squaline–>squaline epoxide; first closed ring struc; goes to 7 dehydrocholesterol, eventually cholesterol w/reductase (after 25 steps); 2 paths to chol from this; main one goes through 7-dehydrocholesterol
Smith-Lemli Opitz synd
mental retardation, microcephaly, malform of heart, lungs, kidney; length of life dep on how much chol can synth; @ reductase from 7-dehydrochol to cholesterol
sterol-dep reg of gene exp
SREBP2 is tx factor bd to ER; proteolytic enz cleaves from ER, travels to nuc, bds to SRE–>activate enz’s like HMG-CoA reductase; when chol high in cell, prev SREBP2 from being cleaved
reg of HMG CoA red by coval mod
glucagon and epi activate a kinase thru cyclic AMP–>phosphorylates reductase, inactivates it; insulin stims phosphatase–>dephos reductase, activates it
SREBP1c
tx factor for lipogenesis; insulin stims protease, so can be cleaved and do fxns
SREBP2
tx factor for chol synth; cholesterol inhibits protease, so cannot do work (so reduce chol synth)
inhibitors of HMG CoA reductase
statin drugs (reversible comp inhibs) - simvastatin/Zocor; atorvastatin/Lipitor; can be toxic b/c prevent isoprenoid synth, which is used in synth of other cmpnds like Q, carotenoids, vit K, E, A, prenylation of prots
bile acids and bile salts
ring of chol can’t be further catab; elim fr body by transport to intestine fr liver or –> bile salts, also sec into intestine; bile prod by hepatocytes–>common bile duct–>intestine
bile
mix of many cmpnds (bile salts, Plipid, phosphatidylcholine, salts, bilirubin, cholesterol); can pass dir from liver to duod thru common bile duct or stored in gallbladder when not immed needed for digest
seq to cholic acid or chendoxycholic acid from chol
add OH to C7; remove 3-C side chain and double bond; add OH to C12; to obtain bile salt, add taurine or glycine to bile acid in amide linkage
bile salts
more effective in emulsifying fat b/c enhanced amphipathic nature w/OH in b or below ring struc and methyl in a or above ring, so polar and nonpolar faces (w/o, fats can’t be digested)
bacteria in intestine
can remove Gly and taurine from bile salts–>regen bile acids
secondary bile salts and acids
formed by axn of bact in intestine, which removes OH from 7 position
