fatty acid oxidation

why is this needed

bc glucose isn’t the best storage molecule

adipocytes

fat cells, filled with lipid droplets that are small collections of fat

triacylglycerols

have 3 CH2 groups, each connected to a fatty acid via an ester linkage
fatty acid tails can be identical or not

important enzyme

phospho/lipase - cleave glycerol and releases the tails as single fatty acids
works in a similar way to chymotrypsin

what happens to fats after being eaten

they’re grouped in the stomach as lipid droplets via the hphobic effect as large fat globules
enzymes can’t access the triacylglycerols

fat digestion steps

1. emulsification

2. lipases act and fats cross

3. remake triacylglycerols

4. package triacylglycerols into chylomicrons

5. lymphatic and circulatory system

step one of fat digestion - fat emulsification

the triacylglycerols are in the fat globules
body releases bile salts and their hphobic side binds to the fat globule so the hydrophilic is on the outside
separates lipid droplets into manageable sizes and makes them moveable

bile salts

are amphipathic - have hphilic and hphobic sides
hphobic sides binds to the fat globule so the hphilic is on the outside

allows for hphobic fat to be transported through our hphilic body

step 2 of fat digestion - lipases

now that the triacylglycerols are in smaller droplets, the lipases can access them and pull out indiv triacylglycerols

lipases cleave them into fatty acids and glycerol

both are then imported across small intestine cell membrane via diffusions

steo 3 and 4 of fat digestion

fatty acids are remade into triacylglycerols in the smooth ER

then packaged into a chylomicron for transport into the lymphatic system

chylomicron

have a layer of phospholipids on the outside - hphobic tails interact with triacylglycerols and hphilic heads allow for movement throughout the body without clogging up blood cells

filled with triacylglycerols and has proteins imbedded in the phospholipid monolayer

step 5 of fat digestion

chylomicrons undergo exocytosis and enter the lacteal, then move throughout the lymphatic system and can enter the blood stream

in blood stream, lipases convert the triacylglycerates into fatty acids and glycerol again until they’re imported into a target

2 target cells for fat digestion

fat cells - converted back into triacylglycerate for longer term storage

muscle cells - oxidized for energy

3 important types of fat

subcutaneous - fat storage, first to be lost in weight loss

visceral - fat under muscles, protects organs

brown - fat that runs etc, makes atp and heat

how to mobilize fat from fat cells for use

low blood sugar signals for glucagon hormone to be released, which binds to receptors on the surface of adipocytes and causes a signal cascade

cascade triggers activation of lipases on the surface of lipid droplets within the cell so they break down triacylglycerols

the fatty acids enter the blood stream and bind to albumin, then enter cells via a transporter and go to the mt

serum albumin

most plentiful rotein in blood plasma by mass

can carry 10 fatty acids and shields the hphobic tails from water

fatty acid oxidation: 1

before entering the mt, the fatty acids (no glycerols) need to be activated by fatty acyl-coa synthase - convert the fatty acid into fatty acyl-coa

uses atp and makes a high energy thioester bond - energetically favorable - and the other 2 phosphate groups are converted into Pi which is also favorable

turns atp → amp and uses coa bc amp and coa are both good lg

don’t need to know mech

fatty acid oxidation: 2

entering the mt is the rate limiting step

fatty acids move from coa to carnitine acyl transferase i to cross the outer mt membrane (bc coa good lg) into the intermembrane space

then fatty acyl carnitine moves into the mt matrix through acyl carnitine transporter protein

fatty acyl transferred back onto a coa by carnitine acyl transferase ii

makes fatty acyl-coa now in the mt

fatty acid oxidation: 3

beta oxidation

takes place in mt, goal is to fully oxidize c in fatty acid and does this by chopping fatty acid glycerols into acetyl coas (2C at a time) and adding a carbonyl (makes bond more unstable)

4 steps of beta oxidation

1. acyl coa dehydr → dehydr to gen 2x bond btwn alpha and beta C

2. enoyl coa hyratase → hydr to add water and make OH on beta C group

3. beta hydroxy acyl coa dehydr → dehydr to gen carbonyl on beta C

4. thiolase → acyl transfer so coa-sh nucleophilic attack and cleaves off acetyl-coa

5. acetyl-coa and fatty acid tail (-2C) are released

2C from fatty acid tail cleaved at a time

identical to last 3 steps of TCA (succinate → fumarate → malate → oaa)

if tail has X number of C

goes through X/2 rounds of beta oxidation, releases (X/2) + 1 acetyl coa

releases X/2 NADH+H and (X/2 - # 2x bonds) FADH2

uses 2((X/2)+1) coa - basically 2*acetyl coa

e- carriers to ATP

1 FADH2 = 1.5 ATP

1 NADH+H = 2.5 ATP

per 1 FADH2 or NADH+H, 0.5 O2 was used in ETC

to find total fatty acid to atp, just multiply w/ num made

acetyl coa to ATP

acetyl coa goes through etc and tca so:

Y acetyl coa → 3*Y NADH, Y FADH2, and Y GTP

GTP ~ ATP energy wise

with unsaturated fatty acids

enzymes need trans double bond to work with BUT most naturally occurring 2x bonds are cis so need to isomerize and shift 2x bond up 1C to make it trans

skip the first step (so no FADH2 generated) and start at the second step

• less saturated fatty acids = less energy bc make less FADH2 (bc the molec is already partially oxidized and less e- to harvest)

how are 2x bonds dealt with

1. beta oxidation occurs as normal (each round = blue squiggle) until reach point where beta C in 2x bond

2. d3, d2-enoyl-coa-isomerase isomerases to get the 2x bond btwn alpha and beta C so it can join the normal path at step 2

beta oxidation yield from one round

CX + coa + FAD + NAD+ + H2O → C(X-2) + acetyl-coa + fadh2 + nadh

overall beta oxidation equation

XC + Y O2 + Z ADP + ZPi + coa → Z ATP + Y H2O + some CO2

under starvation conditions, what happens

oaa is diverted to gng to make more glucose without being replenished from other sources

causes the tca cycle to slow bc dec oaa for fisrt step

inc [acetyl coa] bc not being used and free [coa] dec

causes fatty acid oxidation to dec

how does the body cope with the dec of free coa under starvation

generates ketone bodies that move around in body, which can by used by tissues for energy pdction and regens coa

tissues like brain and muscles and heart but NOT liver cause this happens there

forming ketone bodies

made in liver cell mt

don’t need to know struct

2 acetylcoas get smushed together to make acetoacetyl-coa (releases 1 coa-sh), which gets converted to beta-hydroxy-beta-methylglutaryl-coa when another acetyl-coa and water is added (releases 1 coa-sh). then gets turned into acetoacetate (releases 1 coa-sh) and converted into acetone and beta-hydroxybutyrate (using nadh and releasing co2)

acetone exhaled as waste

ketone bodies

acetoacetate, acetone, beta-hydroxybutyrate

hydroxybutyrate and acetoacetate can be used as fuel but acetone exhaled as waste

why ketone bodies?

1. beta-hydroxybutyrate can be converted back into acetoacetate

2. adding coa activates acetoacetate → acetoacetyl-coa

3. acetoacetyl-coa is cleaved by thiolase to make 2 acetyl-coa

4. that can enter the tca

5. allow for fatty acid oxidation in liver to cont and supply alt fuel