Lightbody Lecture 13

Question 1

cholesterol

Answer 1

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)

Question 2

cholesterol v sitosterol

Answer 2

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

Question 3

HMG-CoA reductase

Answer 3

ctrling enz in chol biosynth; - by statins; rate limiting; reg dir and indir by diff kinds of metab ctrl (HMG-CoA to mevalonate)

Question 4

7-a-hydroxylase

Answer 4

rate limiting rxn in bile acid and bile salt synth; bile salts feed back and inhibit here

Question 5

chol biosynth req

Answer 5

18 mol acetyl-CoA, 36 ATP, 16 NADPH; 30 rxns

Question 6

activated isoprene

Answer 6

precursor of many other metabolites; >20,000 isoprenoids; rubber, phytol chain of chlorophyll, Q, vit K, vit A, vit E, cholesterol, etc.

Question 7

squalene synth

Answer 7

2 x farnesyl pyrophosphate + squalene synthase–>squalene (30C); or isopentenyl-PP + dimethylallyl-PP –> squalene

Question 8

mixed fxn oxygenases

Answer 8

incorp oxy atoms directly into subst

Question 9

dioxygenases

Answer 9

incorp both oxy atoms into substrate

Question 10

monooxygenases

Answer 10

incorp only one atom into substrate; mixd fxn b/c oxidize 2 substrates simult

Question 11

oxidase

Answer 11

uses O2 as e- acceptor, but no oxy incorp into substrate! don’t confuse w/oxygenases…

Question 12

lanosterol

Answer 12

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

Question 13

Smith-Lemli Opitz synd

Answer 13

mental retardation, microcephaly, malform of heart, lungs, kidney; length of life dep on how much chol can synth; @ reductase from 7-dehydrochol to cholesterol

Question 14

sterol-dep reg of gene exp

Answer 14

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

Question 15

reg of HMG CoA red by coval mod

Answer 15

glucagon and epi activate a kinase thru cyclic AMP–>phosphorylates reductase, inactivates it; insulin stims phosphatase–>dephos reductase, activates it

Question 16

SREBP1c

Answer 16

tx factor for lipogenesis; insulin stims protease, so can be cleaved and do fxns

Question 17

SREBP2

Answer 17

tx factor for chol synth; cholesterol inhibits protease, so cannot do work (so reduce chol synth)

Question 18

inhibitors of HMG CoA reductase

Answer 18

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

Question 19

bile acids and bile salts

Answer 19

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

Question 20

bile

Answer 20

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

Question 21

seq to cholic acid or chendoxycholic acid from chol

Answer 21

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

Question 22

bile salts

Answer 22

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)

Question 23

bacteria in intestine

Answer 23

can remove Gly and taurine from bile salts–>regen bile acids

Question 24

secondary bile salts and acids

Answer 24

formed by axn of bact in intestine, which removes OH from 7 position

Question 25

portal vein

Answer 25

reabsorbs 95% of bile salts secreted into intestine

Question 26

enterohepatic circulation

Answer 26

1o and 2o bile salts and acids are transported back to liver via portal v, where reconjugated and resecreted

Question 27

bile acids secreted

Answer 27

20-30g/day, but liver maint pool of 3-5g b/c of tox as detergent, so recirc 4-10x/day

Question 28

gallstones

Answer 28

small amts of free chol transported into bile from liver to intestine; b/c of low solubil, must be accomp by sufficient phosphatidylcholine and bile salts; if more chol enters bile than can be solubilized, will precipitate in GB–>gallstones; risks are over 40, female, obese; no clear rel b/w diet and gallstones

Question 29

hypercholesterolemia

Answer 29

when high blood chol that can’t be ctrl’d by diet and statins, anion exchange resin cholestyramin is given; bile salts bind to resin and eliminate in feces; releases fdbk inhib that inhib bile acid synth from chol, lowering chol in liver, and inc LDL receptor synth allowing more chol to be removed from serum (lowers chol 20%)

Question 30

desmolase

Answer 30

mixed fxn oxygenase, uses cyt P450; present in steroid horm prod cells, RLS; activ’d by prot horms like ACTH or LH from pituitary; removes 6C from chol to make pregnenolone

Question 31

pregnenolone

Answer 31

precursor to all other steroid hormones, but has no hormone activity itself; C21

Question 32

progesterone

Answer 32

from CL, placenta, adrenals and testes as precursor; preps uterine lining for embryo implant; if implant, conc remains high, prev ovulation; otherwise, drops, menstrual period begins; C21

Question 33

glucocorticoids

Answer 33

adrenal cortex (cortisol); stress-induced; reg intermed metab, vasc tone, CNS fxn, devel, apoptosis; also anti-inflam and immune supp effectors, interfere w/every step of imm resp; ACTH stims adrenals to prod cortisol; excess fdbk to inhib ACTH; lack of cortisol results in high conc of ACTH in serum; C21

Question 34

mineralocorticoids

Answer 34

adrenal corex (aldosterone); electrolyte balance in kidneys by promoting reabs of Na and H2O and elim K; C21

Question 35

testosterone

Answer 35

testes and ovaries; devel of male reprod tissue, 2o sex chars (C19)

Question 36

estradiol

Answer 36

ovaries, testes, adipose; devel 2o sex chars in female; regul of menst, bone growth, ovul, etc. (C18)

Question 37

anabolic steroids

Answer 37

testosterone (inc prot synth and bone density; high BP, chol, cardiovasc disease, liver dmg, baldness, mood disorders, aggressiveness, feminization), stanozolol (inc m mass while losing fat, not converted to E; lots of athletes), dianabol (inc m strength, gynecomastia, high BP, masculinizes women)

Question 38

steroid receptors

Answer 38

prots that act as tx factors and bd to promoter regions of response genes; steroid bds recep, then transloc of SR complex to nuc, then bdg of complex to DNA reg site, then tx, then translation