Lightbody Lecture 12

Question 1

E stores in typical body

Answer 1

135000kcal fats (85% of body’s stored E), 24000kcal prot, 720kcal glycogen, 80kcal blood glucose (gluc can last 1 day)

Question 2

beta oxidation

Answer 2

ox of FAs; takes place in mito matrix; FAs broken down into 2C frags (aCoA) which enter TCA or conv to ketone bodies in liver

Question 3

ATGL - adipocyte TAG lipase

Answer 3

hydrolyzes only TAG

Question 4

HSL - hormone sensitive lipase

Answer 4

hydrolyzes TAG and DAG; + by isoproteronol (stims adren receps), + by phos by PKA and PKG (translocates from cyto to perilipin-cont droplets, - by insulin)

Question 5

MGL - monoglyceride lipase

Answer 5

hydrolyzes only MAG

Question 6

acyl CoA synthetase

Answer 6

takes R-COO- FA and ATP, becomes acyl-adenylate intermed, then use again w/CoASH to become acyl-CoA + AMP

Question 7

key process in fat metab

Answer 7

hydrolytic cleavage of stored TAG w/gen of FA and glycerol and their release from adipocytes where they’re transported, complexed w/albumin, to various tissues to be used as E

Question 8

perilipin

Answer 8

coats lipid droplets in adipocytes; acts as protective coating agst lipases; non-phos (coats lipid droplet) or phos (by PKA and PKG, changes conf, exposing stored lipids to HSL)

Question 9

carnitine acyltransferase I

Answer 9

in carnitine shuttle; - by malonyl CoA, makes O-acylcarnitine from L-carnitine, then O-acylcarnitine gets translocated and acyls transferred to move L-carnitine into cell

Question 10

FA activation

Answer 10

after leave adipocytes, transported (att to albumin) to other tissue (m, heart, liver); short and med chain (<12) can x mito memb, activated in matrix; long (12-20) activ at outer mito memb, transported into mito by carnitine shuttle

Question 11

b-oxidation

Answer 11

dehydrogenase w/FAD as e- acceptor, then hydration, then dehydrogenase w/NAD as e- acceptor, then cleave CC bond (thiolase)–>acetyl-CoA and new fatty acyl-CoA w/2 fewer C units

Question 12

b-oxid of palmitic acid (C16)

Answer 12

7 cycles; 131-2 = 129 ATP from activation; in mito matrix

Question 13

2 mito systems of b oxidation

Answer 13

1) fam of memb-bd enz’s spec for long-chain FAs; 2) soluble enz’s in matrix spec for short and med chain FAs; as long shortens, moves from memb-bd complex to soluble matrix enz’s (maj of FAs entering mito are long-chain)

Question 14

metab of odd-chain FAs

Answer 14

propionyl-CoA-carboxylase->D-methylmalonyl-CoA-racemase->L-methylmalonyl-CoA-mutase->succinyl-CoA–>TCA

Question 15

oxid of unsat FAs

Answer 15

almost all unsat FAs cont only cis DBs; hydratase acts only on trans, so need isomerase (oleoyl-CoA; eventually become acetyl-CoA, but need an isomerase to make cis–>trans, then use hydratase

Question 16

carnitine cycle mito fat oxid disorders

Answer 16

involves LCFA transport thru inner mito memb

Question 17

disorders of mito fat oxid in general lead to

Answer 17

cardiomyopathy, hypoglycemia, hypokeosis, myopathy, encephalopathy; defs in carnitine cycle or inner memb can be partially overcome by giving MCFA or SCFA (milk)

Question 18

inner memb sys mito fat oxid disorders

Answer 18

mainly shortening of LCFAs thru b-oxid

Question 19

mito matrix fat oxid disorders

Answer 19

oxids FAs of shorter length, doesn’t involve carnitine

Question 20

artificially induced trans fatty acids

Answer 20

hydrogenate polyunsat cis oils–>bonds that don’t reduce change from cis to trans (margarines) - not oxidized easily, so reduce rancidity, inc shelf life; cont no animal fats; raise LDL, lower HDL; contrib to coron heart dis, cancer, diab, obesity, liver dysfxn

Question 21

ketone bodies

Answer 21

FAs metab to acetyl-CoA by b-ox, then condense to form KBs; synth ONLY in liver mito; secreted into blood, transported to other tissue (heart, m, kidney, brain), reconv to acetyl-CoA, used as E; liver cannot metabolize them!; synth small quant all the time, but in starvation, unctrl’d diab I synth in lg quants

Question 22

synth of ketone bodies

Answer 22

acetyl-CoA–>acetoacetylCoA–>3-hydroxy-3-methylglutaryl-CoA (HMG-CoA–also in chol synth)–>acetoacetate–>acetone + b-hydroxybutarate

Question 23

metab of ketone bodies

Answer 23

water sol equiv of FAs; brain can use in starvation

Question 24

thiophorase

Answer 24

needed to metab KBs; liver deficient in this, so can only synth, not metab!

Question 25

fasting, starvation, severe T1D

Answer 25

OAA (via malate) leaves mito, used for glucose synth (GNG)-->shuts down TCA; at time, liver prod A-CoA by b-ox of FAs, but has nowhere to go, so condenses to KBs; glc levels maint by glycerol, RBC lactate, AA brkdn (major source)

Question 26

KB utilization

Answer 26

rel into systemic blood (acetone elim in urine, exhaled; acetoacetate and b-hydroxybutarate used as fuels); convert to E (b-hydroxybut and acetoacetate conv to acetoacetyl CoA using succ CoA from TCA; cleaved to 2-acetyl-CoA); range of tissues can use (brain when starved, thiophorase induced after 4d of starvation, derive 50% of E from KB); excess-->acidosis, relieved thru elim of KBs thru urine

Question 27

Atkins

Answer 27

high fat, low carbs-->fat mobil and KBs in urine; active fat metab and GNG; check for KB in urine-->sign that fat metab; discouraged b/c metabolic acidosis

Question 28

KBs and T1D

Answer 28

diab-->high glc in blood; transport into tissues reduced; resp by inc GNG in liver, inc TAG brkdn in adipocytes; FAs transp to liver for ox, consuming most of OAA; no OAA, so excess a-CoA condenses-->KBs (detect acetone on breath)

Question 29

peroxisomes

Answer 29

synth bile acids, lipids, H peroxide, detox; live a few days; brkdn VLCFAs (C22-30), both sat and unsat; cont all b-oxid enz's (enz that activates VLCFA (acylCoA synthetase) only in this organelle); have sep transporter, so don't need carnitine; b-oxid only goes a few cycles, then rel'd to mito for further oxid

Question 30

catalase

Answer 30

degrades H2O2 in peroxisome; 2H2O2-->2H2O + O2; don't prod ATP

Question 31

FADH2 in peroxisome

Answer 31

gen'd by b-oxid; reox-->H peroxide; difers from mito where this enters e-transport chain (FADH2 + O2 --> FAD + H2O2)

Question 32

NADH formed in peroxisome

Answer 32

can't be reox here, so has to be exported out

Question 33

A-CoA formed in peroxisome

Answer 33

must transfer out b/c TCA cycle enz's absent

Question 34

X-ALD

Answer 34

dec in abil for peroxisomes to degrade VLCFAs, so build up in adrenal, brain, plasma, fibroblasts-->interfere w/abil of adrenal to conv chol into steroid, demyelin nn in brain; appear @4-10yo (behav /\, bad vision, hearing, coord); death 2-4y later

Question 35

X-ALD defect

Answer 35

ATP bdg ABCD1 transporter prot (ALDP), crucial for transport of VLCFAs into peroxisomes; treat w/Lor oil or stem cell therapy

Question 36

Lorenzo's Oil

Answer 36

4:1 mix of oleic acid and erucic acid from olive and rapeseed oil; must give before symps present, low fat diet; retard disease (maj of VLCFAs accum are sat FAs from diet and synth)

Question 37

elongase

Answer 37

synth saturated VLCFAs; elongates both sat and unsat FAs; monounsat FAs compete for this enz, lowering synth of sat VLCFAs