Lightbody Lecture 11 Flashcards Preview

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Flashcards in Lightbody Lecture 11 Deck (38):
1

TG energy

9 kcal/g; no osmotic effect (anhydrous)

2

carb energy

4.5 kcal/g

3

lipogenesis

from excess calories from carbs or sometimes protein; conv to FAs in liver, stored in adipose as triglycerides

4

enz's for FA synth

in cytoplasm; use NADP

5

enz's for FA oxid

in mito; use NAD

6

FA nomenclature

position of double bonds are counted from carboxyl end

7

w (omega) nomenclature

counting double bond position; count from methyl end

8

citrate shuttle

provides acetyl-CoA for FA synthesis (from mito to cyto)

9

pyruvate carboxylase

pyruvate-->OAA, take ATP and HCO3- and release ADP+Pi

10

acetyl-CoA carboxylase (ACC)

biotin carrier prot, biotin carboxylase, transcarboxylase; bicarb is phos'd, then picked up by biotin, which transfers CO2 to acetyl-CoA to form malonyl CoA

11

ACC regulation

allosteric (+ by citrate, - by palmitoyl coA); phosphorylation (unphos-->inc'd polym by citrate; phos-->inc depolym by palm CoA); insulin activates phosphatase (inc activity); epi and glucagon activ kinase (dec activity)

12

human FA synthase

homodimeric, multienz; 270kD, 6 enz's; 2 monomers linked head to tail; first 2 enz activities are on one chain, rest switches to other chain; only synths FAs at or below palmitic acid (C-16)

13

malonyl-CoA-acetyl-CoA ACP transacylase (MAT)

only ACoA step! all others are mal CoA

14

cancer

use de novo synth vs dietary lipid synth b/c rapid cell div; metab lg quants of glucose-->lots of pyruvate-->lactate/aCoA (used for FA synth for memb synth); high level of FAS (poor prognosis; and FAS inhib is selec toxic to human cancer cells, w/little effect in normal cels)

15

FA elongation

FA from FAS is palmitate (C-16 w/o saturation); elongation fr ER enz's, esterified to coA, used as substrates (mal CoA donates 2-C units); fatty acid elongases (ELOVL) cat initial condensation (add 2 Cs from carboxyl end)

16

desaturation/intro double bonds

occurs in ER; 4 broad-spec fatty acyl-CoA desaturases; intro dub bds at 4, 5, 6, or 9--NONE BEYOND C9; always in cis

17

essential FAs

linoleic acid (dbs at 9,12) and linolenic acid (dbs and 9, 12, 15); must get from plants that can synth beyond C9; some fish too (from plankton)

18

arachidonic acid

C-20:4 /\5,8,11,14 can be synth'd from linoleic acid by chain elong and desat; otherwise, must get from diet; needed for eicosanoid synth

19

lipogenesis regulation

ACC and SREBPs

20

SREBP

+ >30 genes assoc w/synth of chol, FAs, TGs, Plipids and NADPH (req'd to synth molecs); synth as inactive precs bd to ER, released by ser protease, transloc to nucleus (bd to sterol response element in promoter region); 1c activ tx of genes req for synth of FAs and Plipids; 2 activ tx of genes for chol synth

21

SREBP 1c

activs tx of genes for FA and Plipid synth; protease hydrolyzes product off ER (where synth'd) so becomes free to enter nucleus; protease + by insulin, so axn of prot + by insulin

22

BAT

maint T; lipid are mini-droplets; lots of mito

23

WAT

as TAG accums here, cells grow larger; when reach max size, divide; preadipose cells-->mature adipocytes; enlgmt and divis cont as long as TAG accum; obese: lg adipocytes necrose-->attract macs

24

cytokine vs adipokine

prots used for cell-cell signaling vs former synth'd by adipocytes

25

deregulation of adipocyte-secreted factors

leads to disease states (cardiovasc disease, insulin resistance)

26

leptin

ob locus encodes this; defective-->ravenous appetite, obesity, insulin res, fatty liver, defective thyroid metab (dec if inject hormone); adipokine, but also made in stomach, mamm, placenta, skel m; recep is in liver, musc, hypothal; mutations prod same symps as mutations in ob gene; free and bound forms; 3o struc like cytokine fam; 16kDa; more adipocytes, more of this prod; fast or diet-->levels dec, appetite inc

27

physio leptin effects

regul food intake, E expend, body wt; thermogenesis, reprod fxn, supp bone form, directly act on liver and m cells, rel to inflam resp, contrib to early hematopoiesis

28

leptin in hypothal

effects mediated thru arcuate nucleus; KO mice show same metab symps as mice w/non-fxnal ob gene

29

NPY (neuropeptide Y) in arcuate nuc

prod NPY and AgRP (agouti-rel prot); both inc appetite, dec metab; orexigenic (ghrelin up, leptin down)

30

POMC in arcuate nuc

prod a-MSH (dec appetite, inc metab); anorexigenic (leptin up)

31

leptin resistance hypotheses

adipocytes and macs fr obese prod toxic factors like inflam cytokines that inhib leptin fxn; hypothal prod SOCS3 (inhib leptin signaling); defect in cmpnnt of signaling path for leptin; dereg of 2o neurons in leptin signal path; receps downregulated in hypothalamus

32

adiponectin (APN)

244-AA prot, synth and sec by adipocytes, high concs in plasma; dir axn on liver, skel m, vasculature; levels inversely prop to body fat; further dec in obesity, insulin res, T2DM, heart disease, atherosclerosis, inflam; TNF-a suppresses/inhibits prod

33

adiponectin axn

periph treatment dec body fat by enhancing E expend and FA oxid (like leptin); chronic treatment w/this reduces food intake, weight, glucose; may act thru hypothal like leptin

34

AMPK-kinase

phosphorylates ACC, deactivating it

35

malonyl-CoA

prevents FAs from entering mito; adiponectin inhibits this so FAs can enter mito and go through b-oxid

36

insulin

regulates fat and carb metab; activates SREBP-1; inc GLUT activity in m and adipocytes (not liver)

37

insulin resistance

caused by obesity in T2DM; cont to synth glucose even though lots around, lots of insulin around, lots of TAGs (would normally shut off); decrease APN (-->inc insulin res); no glucose entering musc or adipocyte; excess fat in liver and musc, excess FFAs in serum, adipose, musc, and liver

38

obese adipocytes lead to

inflam cytokines (TNFa, IL6, IL1-->inflam stress, inhib insulin stim glucose uptake); dec in adiponectin (insulin res, dec in fat met, dec in E exp); high conc of FFAs in serum (metab stress, interfere w/insulin inhib of GNG, prev glycolysis in m, causes ER stress-->accum unfolded prots, dec prot synth, activ prot degrading signals)