Lightbody Lecture 13 Flashcards Preview

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Flashcards in Lightbody Lecture 13 Deck (38):
1

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)

2

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

3

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)

4

7-a-hydroxylase

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

5

chol biosynth req

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

6

activated isoprene

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

7

squalene synth

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

8

mixed fxn oxygenases

incorp oxy atoms directly into subst

9

dioxygenases

incorp both oxy atoms into substrate

10

monooxygenases

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

11

oxidase

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

12

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

13

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

14

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

15

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

16

SREBP1c

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

17

SREBP2

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

18

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

19

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

20

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

21

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

22

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)

23

bacteria in intestine

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

24

secondary bile salts and acids

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

25

portal vein

reabsorbs 95% of bile salts secreted into intestine

26

enterohepatic circulation

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

27

bile acids secreted

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

28

gallstones

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

hypercholesterolemia

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

desmolase

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

pregnenolone

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

32

progesterone

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

glucocorticoids

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

mineralocorticoids

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

35

testosterone

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

36

estradiol

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

37

anabolic steroids

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

steroid receptors

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