Lightbody Lecture 11

Question 1

TG energy

Answer 1

9 kcal/g; no osmotic effect (anhydrous)

Question 2

carb energy

Answer 2

4.5 kcal/g

Question 3

lipogenesis

Answer 3

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

Question 4

enz’s for FA synth

Answer 4

in cytoplasm; use NADP

Question 5

enz’s for FA oxid

Answer 5

in mito; use NAD

Question 6

FA nomenclature

Answer 6

position of double bonds are counted from carboxyl end

Question 7

w (omega) nomenclature

Answer 7

counting double bond position; count from methyl end

Question 8

citrate shuttle

Answer 8

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

Question 9

pyruvate carboxylase

Answer 9

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

Question 10

acetyl-CoA carboxylase (ACC)

Answer 10

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

Question 11

ACC regulation

Answer 11

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)

Question 12

human FA synthase

Answer 12

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)

Question 13

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

Answer 13

only ACoA step! all others are mal CoA

Question 14

cancer

Answer 14

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)

Question 15

FA elongation

Answer 15

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)

Question 16

desaturation/intro double bonds

Answer 16

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

Question 17

essential FAs

Answer 17

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)

Question 18

arachidonic acid

Answer 18

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

Question 19

lipogenesis regulation

Answer 19

ACC and SREBPs

Question 20

SREBP

Answer 20

+ >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

Question 21

SREBP 1c

Answer 21

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

Question 22

BAT

Answer 22

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

Question 23

WAT

Answer 23

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

Question 24

cytokine vs adipokine

Answer 24

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

Question 25

deregulation of adipocyte-secreted factors

Answer 25

leads to disease states (cardiovasc disease, insulin resistance)

Question 26

leptin

Answer 26

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

Question 27

physio leptin effects

Answer 27

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

Question 28

leptin in hypothal

Answer 28

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

Question 29

NPY (neuropeptide Y) in arcuate nuc

Answer 29

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

Question 30

POMC in arcuate nuc

Answer 30

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

Question 31

leptin resistance hypotheses

Answer 31

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

Question 32

adiponectin (APN)

Answer 32

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

Question 33

adiponectin axn

Answer 33

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

Question 34

AMPK-kinase

Answer 34

phosphorylates ACC, deactivating it

Question 35

malonyl-CoA

Answer 35

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

Question 36

insulin

Answer 36

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

Question 37

insulin resistance

Answer 37

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

Question 38

obese adipocytes lead to

Answer 38

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)