L1 - Intro Lipid Catabolism

fat’s HC tails are ___, which provides ____

highly reduced, high oxidation energy

nonpolar, weak CH bonds, insoluble in water

they contain lots of energy bc many CH bonds

TAGS (do/not) raise osmolarity of cytosol, and are not ____

do not; hydrated

they are water insol so don’t change osmolarity (solute / solution)

they are like rocks in water, change volume but not dissolution

lipid catabolism major idea

TAG > 3FA + glycerol backbone

• FA > ACoA/MeACoA (even / uneven) > CAC/Krebs Cycle

• Glycerol > DHAP > Glycolysis / Gluconeogenesis

in catabolism, FA turn into

somethingCoA through beta oxidation,

CoA goes into Krebs to make energy

in catabolism, glycerol goes

to glycolysis as DHAP, then Krebs for energy

lipid anabolism major idea

ACoA > 3FAs > TAG / Plipid / Sphingolipid > cholesterol

ACoA > HMGCoA > Ketone bodies / steroids/bile acids

Dietary fat turns into

TAGs

Stored fats turn into

FFAs (they are already TAGs)

both dietary and stored fats are ____ and converted into ____

transported;

FA-CoA > FA-carnitine (mitoC) > FA-CoA > B-oxidation

this is for beta oxidation FA, part of which is in matrix so must be transported from cytoplasm and back

Step by Step Dietary Fats

1. Bile acids in intestine digest to form micelles

2. Intestinal lipases degrade TAGs by Hlyze ester bond

3. Intestinal FFA + glycerol > TAG

4. intestinal TAGs transported with chylomicron w/ cholesterol and apolipoproteins

5. chylomicrons move through blood

6. in tissue, activated lipoprotein lipase TAG > FA + glycerol

7. absorption in target tissue

fats from diet are used ____ or ____

boxidation; turned into stored fat and then eventually catabolized

step 1 dietary catabolism

bile salts break fats in SI, form micelles to increase SA

step 2 dietary catabolism

lipases TAG > FA + glycerol, go into enterocytes (intestine lining)

hydrolyze ester bond

step 3 dietary catabolism

FA taken into mucosa and > TAGs

step 4 dietary catabolism

TAGs added to cholesterol and apolipoproteins, into chylomicrons for blood transport

step 5 dietary catabolism

chylomicrons move through lymphatic / blood to tissue

step 6 dietary catabolism

lipoprotein lipase activated by apoc2 turns TAG > FA + glycerol

step 7 dietary catabolism

FA and glycerol enter tissues to be oxidized or stored as TAGs

chylomicrons

covered in apolipoproteins

single leaflet

exogenous

apolipoproteins

are recognized and activate lipases to break down TAGs

apoCII in capillary converts TAG > FA + Gy

stored fat catabolism steps

1. Ggon from pancreas, GPCR,

2. adenyl cyclase, ATP > cAMP plates pKA

3. PKA Plates HSL

4. PKA Plates perilipins

5. CGI58 leaves Plated perilipins, activating ATGL

6. ATGL + TAG > DAG + FA

7. HSL + DAG > MAG + FA

8. MGL + MAG > FA

9. FA > glycerol OR carried by serum albumin and transported into myocyte

10. FA are B-oxidized, Krebs, respiration,

11. FA breakdown produces ATP and CO2

step 1 TAG catabolism

pancreas sends glucagon to a GPCR

step 2 TAG catabolism

adenyl cyclase turns ATP into cAMP, which activates PKA

step 3 TAG catabolism

PKA Plates HSL, activating it

step 4 TAG catabolism

PKA Plates perilipins, removing CGI58

step 5 TAG catabolism

CGI58 activates ATGL

step 6 TAG catabolism

ATGL turns TAG > DAG + FA

step 7 TAG catabolism

HSL turns DAG into MAG + FA

step 8 TAG catabolism

MGL turns MAG into FA + glycerol

step 9 TAG catabolism

FA transported from fat to heart via serum albumin carriers in blood

step 10 TAG catabolism

FA transported in, are Boxidized, Krebs, ETC, whatever

final step TAG catabolism

produce ATP CO2 in heart cell

FA Oxidation / Activation

FACoASase + FA + CoASH + ATP > FACoA + AMP + 2Pi

activates FA for energy bond > B-oxidation

-G; final step in FA synthesis

B oxidation occurs in the ____, but FAs are in ___, so they must be converted to _____ and use a ____

mitochondria; cytosol; carnitine; transporter

carnitine acyltransferase

***1 - In (gets FA in), 2 = step 2 (return)

catalyzed B-oxidation step, major regulatory checkpoint

I = FACoA + ACoA in cytoS > Acarnitine + CoASH in mitoC

II = carnitine + CoASH in mitoC > FACoA + carnitine in cytoS

B-oxidation steps (know general not specific)

4 steps, 16C > 14C, oxidation, hydration, oxidation, cleavage > ACoA

7 total rounds, yields 8 ACoA (16 > 2)

****palm is ox by acylCoADH, TransEnoylCoAHase, BHACoADHase, ACoAATrase (thiolase) into acylCoA + ACoA, makes 4e-, repeats steps 4 times 7 rounds, 8ACoA

***P ACDH TECH BHCDH ACAT, please all cool dudes have TECH but half cool dudes have ACAT

Stage 1: B-Oxidation = breakdown of long FA > ACoA

1. Oxidation = single bond > double bond next to C=O

   AcylCoADH + palmitoylCoA(16C) + FAD > trans EnoylCoA + FADH2

2. Hydration = C=C > COH

   trans EnoylCoA Hase + H2O > LBHACoA

3. Oxidation = OH > =O

   BHACoAcylDH + LBHAcylCoA + NAD+ > BKAcylCoA + NADH

4. CoA Attack

   ACoAAT(thiolase) + BKAcylCoA + CoASH > AcylCoA(14C) + ACoA

B-oxidation energy summary

PCOA + 7CoA + 7FAD + 7NAD+ + 7H2O > 8ACoA + 7FADHs + 7NADH + H+

7FADH2 + 7NADH = 28ATP

aCoADH flavoprotein (general idea)

used in PDH complex to reduce FAD, oxidation of FA and AA, contributes to ATP

B-oxidation produces water how?

ETC;

FA broken down in cytoS/mitoC to make AcetylCoA, for Krebs, NADH FADH2, ETC

bile salts

Amphipathic molecules derived from cholesterol in the liver and stored in the gallbladder.

emulsify DAGs in the SI, forming micelles

lipases

Hlyze TAGs into MAGs + FFA.

pancreatic lipase in intestine

chylomicrons

lipoproteins formed in intestinal epithelial cells.

transport dietary TAGs, cholesterol, and fat-soluble vitamins through the lymph and bloodstream to tissues like muscle and adipose.

hormone sensitive lipase

IC enzyme in fat

Hlyzes stored TAGs > FFA + glycerol

activated by hormones like epinephrine and glucagon.

perilipin

A protein coating lipid droplets in fat cells,

regulating access of lipases to the stored lipids.

When phosphorylated by PKA, it allows HSL access to the droplet.

CGI58

A coactivator of ATGL

initiate TAG breakdown by stimulating ATGL activity.

ATGL

Adipose Triglyceride Lipase

first enzyme in lipolysis

cat. Hlysis of TAG to DAG + FFA

MAGL

Monoacylglycerol Lipase

completes lipolysis by Hlyzing MAG into glycerol + FFA

TAG v DAG v MAG

(TAG): main form of stored fat

(DAG): A breakdown intermediate of TAG

(MAG): A lipid with a single fatty acid chain attached to glycerol; formed during digestion and lipolysis.

serum albumin

A plasma protein that binds and transports FFA in the bloodstream from fat to tissues needing energy.

FA Acyl-CoA Synthetase

activates FFA by + them to CoA,

forming fatty acyl-CoA, which is required for mitochondrial β-oxidation.

carnitine

small molecule, shuttles long-chain fatty acyl-CoAs into the matrix via carnitine shuttle.

carnitine acyl transferase I (CAT1 / CPT1)

outer mitoC mem enzyme transfers the fatty acyl group from CoA to carnitine.

inhibited by malonyl-CoA.

carnitine acyl transferase II (CAT2 CPT2)

enzyme on the inner mitoC mem that transfers the fatty acyl group from carnitine back to CoA inside the matrix,

reforming fatty acyl-CoA for oxidation.

palmitoyl CoA

16C sat fatty acyl-CoA

model substrate for studying β-oxidation.

HMGCoA

3-hydroxy-3-methylglutaryl-CoA

A metabolic intermediate.

• In mitoC, it's part of ketogenesis;

• in the cytoS, it's involved in cholesterol synthesis.

AcylCoA DHase

first enzyme of β-oxidation; cat. the DH of fatty acyl-CoA,

forming a trans double bond between the α and β carbons.

Enoyl CoA DHase

second enzyme in β-oxidation;

adds water across the trans double bond to form L-β-hydroxyacyl-CoA.

HMGCoA DHase

converts HMG-CoA to acetoacetate in the ketogenesis pathway.