L10: Fatty Acid Catabolism

Question 1

3 sources of fatty acids for catabolism

Answer 1

1. diet
2. stored fats (triacylglycerols in adipocytes)
3. newly synthesised fats (triacylglycerols that body makes)

Question 2

structure of TAGs

Answer 2

3 long chain fatty acid chains esterified to glycerol backbone

Question 3

3 stages of f.a catabolism : overall

Answer 3

1. long chain fatty acids catabolised to acetly units in form of Acetly CoA (called beta oxidation)
2. Acetly groups oxidised in TCA cycle
3. Electrons derived from oxidations of STages 1&2 pass to O2 via mitochondrial respiratory chain. ATP synthesis by oxidative phosphorylation

Question 4

where does stage one f.a catabolism occur

Answer 4

mitochondrial matrix

Question 5

3 steps of stage 1 f.a catabolism: overall

Answer 5

1. mobilisation of stored TAGs from adipocytes
2. f.a activation & transport into mitochondrial matrix
3. beta oxidation pathway

Question 6

step 1: monilisation of stored TAGs from adipocytes

where are TAGs stored in fat cells

Answer 6

in lipid droplets

Question 7

step 1: monilisation of stored TAGs from adipocytes

what is the surface of the lipid droplet covered in & what is its purpose

Answer 7

coated with perilipin (a protein), restricts untimely access to TAGs

Question 8

step 1: monilisation of stored TAGs from adipocytes

what is secreted in response to low blood [glucose]

Answer 8

adrenaline & glucagon

Question 9

step 1: monilisation of stored TAGs from adipocytes

what do adrenaline & glucagon bind to & activate

Answer 9

bind to receptors on adipocytes
this activates adenylyl cyclase

Question 10

step 1: monilisation of stored TAGs from adipocytes

what does the activation of adenylyl cyclase increase

Answer 10

[cAMP]

Question 11

step 1: monilisation of stored TAGs from adipocytes

what does increased [cAMP] activate

Answer 11

PKA

Question 12

step 1: monilisation of stored TAGs from adipocytes

what does PKA do

Answer 12

1. phosphotylates perilipins & other proteins - open the lipid droplets
2. allows activity of cytosolic lipases including hormone sensitive lipase

Question 13

step 1: monilisation of stored TAGs from adipocytes

function of the cytosolic lipases

Answer 13

degrade TAGs to liberate fatty acids

Question 14

step 1: monilisation of stored TAGs from adipocytes

what do the lipases hydrolyse in tri/do/mono-acylglycerol

Answer 14

all the lipases hydrolyse ester linkages to liberate fatty acids

Question 15

step 1: monilisation of stored TAGs from adipocytes

overall step 1 description

Answer 15

• adrenaline & glucagon secreted when blood [glucose] low
• bind to receptors on adipocytes
• activat adenylyl cyclase which increases [cAMP]
• this activates PKA
• PKA phosphorylases perilipins & other proteins that open lipid droplet
• allows activity of 3 cytosolic lipases including hormone sensitive lipase
• these degrade TAGs to liberate fatty acids

Question 16

what happens to the fatty acids once liberated before step 2

Answer 16

transported to blood where they bind to serum albumin & are carried to tissues when energy needed

Question 17

how do fatty acids go through into cytosol of cells which need energy

Answer 17

fatty acid transporter protein

Question 18

what kind of f.a chains can enter the mitochondria without help

Answer 18

chains less than 14 carbons long

Question 19

how do fatty acid chains over 14 carbons get into mitochondria

Answer 19

have to be helped in by enzymes & transporter proteins in inner mitochondrial membrane

Question 20

step 2a ; f.a activation

how are f.as activated

Answer 20

by CoA add ons using fatty acyl-CoA synthetase enzymes

Question 21

step 2a ; f.a activation

f.a activation equation and delta G’0

Answer 21

Fatty Acid + CoA + ATP –> Fatty Acyl-CoA + AMP + PPi
(in presence of fatty acyl-CoA synthetase)
delta G’0 = -34KJ/mol

Question 22

step 2a ; f.a activation

what does fatty acyl-CoA synthetase do

Answer 22

catalyses formation of thioester linkage between the carboxyl group of the F.A and the thiol group of coenzyme A to yield a fatty acyl-CoA

Question 23

step 2b: transport to mitochondrial matrix

step 1 of transportation

Answer 23

the fatty acyl-CoA bond is hydrolysed and fatty acyl group attaches to the -OH of carnitine in outer mitochondrial membrane

Question 24

step 2b: transport to mitochondrial matrix

what is step 1 of transportation catalysed by

Answer 24

catalysed by carnitine acyl-transferase-1

Question 25

# step 2b: transport to mitochondrial matrix step 2 of transportation

Answer 25

fatty acyl-carnitine enters mitochondrial matrix through carnitine transporter

Question 26

# step 2b: transport to mitochondrial matrix step 3 transportation

Answer 26

fatty acyl group enzymatically transferred to intramitochondrial CoA by carnitine acyl-transferase-1

Question 27

# step 2b: transport to mitochondrial matrix step 4 transportation

Answer 27

carnitine re enters intermembrane space and process restarts

Question 28

# step 3; beta oc=xidation pathway enzyme 1

Answer 28

dehydrogenase

Question 29

# step 3; beta oxidation pathway what happens in step 1

Answer 29

* dehydrogenase * removes 2H+ to FAD ->FADH2 * d bond produced between alpha and beta carbon * 1 FADH2 formed

Question 30

# step 3; beta oxidation pathway enzyme 2

Answer 30

hydratase

Question 31

# step 3; beta oxidation pathway what happens step 2

Answer 31

* hydratase * H2O added to alpha and beta double bond * 1 H2O input

Question 32

# step 3; beta oxidation pathway enzyme 3

Answer 32

dehydrogenase

Question 33

# step 3; beta oxidation pathway what happens step3

Answer 33

* dehydrogenase * removes 2H+ from beta carbon to NAD+ -> NADH + H+ * 1NADH and H+ formed

Question 34

# step 3; beta oxidation pathway enzyme 4

Answer 34

thiolase

Question 35

# step 3; beta oxidation pathway what happens step 4

Answer 35

* thiolase * splitting off of terminal acetyl CoA w entry of new CoA-SH * 1 acetly CoA formed and 1 CoA input

Question 36

how much energy is obtained in beta oxidation (what delivers electrons to repiratory chain & how many acetyl CoA enter TCA

Answer 36

* 7FADH2 and 7NADH deliver electrons to respiratory chain * 8 acetyl CoA enter citric acid cycle * delta G'0= -9800KJ/mol for complete oxidtion of 1 palmitate

Question 37

what is needed to deal with the d bonds in some fatty acids

Answer 37

* isomerase converts cis (H atom same side as d. bond) -> trans configuration * reductase needed for polyunsaturated fatty acids