Lightbody Lecture 13 Flashcards Preview

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1
Q

cholesterol

A

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)

2
Q

cholesterol v sitosterol

A

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

3
Q

HMG-CoA reductase

A

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

4
Q

7-a-hydroxylase

A

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

5
Q

chol biosynth req

A

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

6
Q

activated isoprene

A

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

7
Q

squalene synth

A

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

8
Q

mixed fxn oxygenases

A

incorp oxy atoms directly into subst

9
Q

dioxygenases

A

incorp both oxy atoms into substrate

10
Q

monooxygenases

A

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

11
Q

oxidase

A

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

12
Q

lanosterol

A

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

13
Q

Smith-Lemli Opitz synd

A

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

14
Q

sterol-dep reg of gene exp

A

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

15
Q

reg of HMG CoA red by coval mod

A

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

16
Q

SREBP1c

A

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

17
Q

SREBP2

A

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

18
Q

inhibitors of HMG CoA reductase

A

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

19
Q

bile acids and bile salts

A

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

20
Q

bile

A

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

21
Q

seq to cholic acid or chendoxycholic acid from chol

A

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

22
Q

bile salts

A

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)

23
Q

bacteria in intestine

A

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

24
Q

secondary bile salts and acids

A

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

25
Q

portal vein

A

reabsorbs 95% of bile salts secreted into intestine

26
Q

enterohepatic circulation

A

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

27
Q

bile acids secreted

A

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

28
Q

gallstones

A

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

29
Q

hypercholesterolemia

A

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%)

30
Q

desmolase

A

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

31
Q

pregnenolone

A

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

32
Q

progesterone

A

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

33
Q

glucocorticoids

A

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

34
Q

mineralocorticoids

A

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

35
Q

testosterone

A

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

36
Q

estradiol

A

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

37
Q

anabolic steroids

A

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)

38
Q

steroid receptors

A

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