lipid degradation: fat digestion + mobilization

Question 1

water soluble enzymes have a difficult time accessing fats for beta oxidation. how do we combat this?

Answer 1

the fats must be emulsified first

Question 2

what does movement of fats through the blood require

Answer 2

requires associated water soluble proteins

Question 3

stable C-C bonds require activation by ___ before oxidation

Answer 3

CoA

Question 4

why is it called b-oxidation

Answer 4

CoA binds to the carboxyl at C1 first. This allows oxidation at C3, aka the b carbon

Question 5

list 4 sources of fatty acids for b oxidation

Answer 5

fats in the diet, fats stored in cells as lipid droplets, fats synthesized in the liver from excess carbs that can be exported elsewhere, fats obtained by autophagy (recycled lipids from an organelle membrane)

Question 6

humans in industrialized countries get __% of energy from dietary fats

Answer 6

40%

Question 7

how does starvation affect autophagy in energy production

Answer 7

starvation can increase the use of autophagy

Question 8

lipid droplets in adipocytes are full of ____ and ____

Answer 8

cholesteryl esters and TAGs

Question 9

T or F: lipid droplets in adipocytes are surrounded by a phospholipid bilayer

Answer 9

false; they’re surrounded by a phospholipid monolayer

Question 10

what are perilpins?

Answer 10

they’re proteins that cover the monolayer membrane of lipid droplets in adipocytes

Question 11

function of perilipins?

Answer 11

they prevent lipid degradation (they protect the lipid droplets in adipocytes)

Question 12

perilipins are bound to an accessory protein called ___

Answer 12

CGI

Question 13

list two hormones that signal the need to bring TAGs out of storage and use them for energy

Answer 13

glucagon and epinephrine

Question 14

why does glucagon serve as a signal to bring TAGs out of storage + use for energy

Answer 14

you’re hungry = need to access TAGs for energy

Question 15

why does epinephrine serve as a signal to bring TAGs out of storage + use for energy

Answer 15

needed for adrenaline = require TAGs for energy

Question 16

describe briefly what needs to happen to bring TAGs out of storage + use them for energy

Answer 16

hormone signals need to remove perilipin from the lipid droplet surface, and then TAGs need to be cleaved into free FAs to move through the bloodstream

Question 17

describe the steps leading up to perilipin dissociation from CGI protein on lipid droplets

Answer 17

glucagon is involved in a GPCR/G protein signalling pathway, producing adenylyl cyclase, which in turn produces cAMP from ATP. cAMP stimulates PKA, which phosphorylates Hormone Sensitive Lipase (HSL) and perilipins. Phosphorylated perilipins dissociate from CGI protein

Question 18

in the pathway of perilipin dissociation from CGI (to access TAGs for energy), what two things does PKA phosphorylate to release perilipin

Answer 18

Hormone Sensitive Lipase (HSL) and perilipin

Question 19

in the pathway of perilipin dissociation from CGI (to access TAGs for energy), describe the steps that occur once perilipin is no longer bound to CGI

Answer 19

CGI activates ATGL, which converts TAGs into DAGs. Phosphorylated HSL-perilipin converts DAGs into MAGs. MGL converts MAGs to free FA + glycerol. Free FAs leave adipocyte and travel through the blood bound to serum albumin, and will enter target tissues by a FA transporter

Question 20

in the pathway of perilipin dissociation from CGI (to access TAGs for energy), what is ATGL and what does it do

Answer 20

adipose TAG lipase. It converts TAGs to DAGs

Question 21

in the pathway of perilipin dissociation from CGI (to access TAGs for energy), what converts DAGs to MAGs

Answer 21

phosphorylated HSL-perilipin

Question 22

in the pathway of perilipin dissociation from CGI (to access TAGs for energy), what converts MAGs to FAs+glycerol

Answer 22

MGL: MAG lipase

Question 23

in the pathway of perilipin dissociation from CGI (to access TAGs for energy), why must free FAs travel through the blood bound to serum albumin

Answer 23

without the serum albumin, FA is too hydrophobic to be able to travel through the blood

Question 24

where is serum albumin produced

Answer 24

the liver

Question 25

how many fatty acids can one serum albumin bind to

Answer 25

7

Question 26

what target tissues does albumin bring FAs to

Answer 26

skeletal muscle, heart, kidney

Question 27

what happens to serum albumin when there is high blood glucose

Answer 27

it becomes glycated

Question 28

what is glycation

Answer 28

the non-enzymatic addition of reducing sugar products to amine groups on proteins and disrupts protein function + can contribute to tissue damage

Question 29

T or F: glycation involves enzymes to reduce sugar products to amine groups on proteins

Answer 29

false; no enzymes are required

Question 30

is glycation good or bad? explain

Answer 30

bad: if you have a lot of sugars in your blood and they start randomly sticking to stuff like serum albumin, the function of serum albumin will be disrupted

Question 31

list 4 diabetes symptoms that glycated albumin contributes to

Answer 31

retinopathies, renal disease, coronary heart disease, neuropathies

Question 32

glycerol only represents __% of the total energy stored in TAGs

Answer 32

5%

Question 33

after FAs and glycerol are released from lipid droplets, where does the glycerol go

Answer 33

to the liver

Question 34

list 2 things that can happen once glycerol from broken down lipid droplets is shipped to the liver

Answer 34

1. it can be phosphorylated and oxidized to DHAP, which can be used for glycolysis or GNG 2. it can be phosphorylated by glycerol kinase to make glycerol-3-phosphate for glycerophospholipid synthesis

Question 35

once glycerol from broken down lipid droplets is in target tissues, where does it need to go

Answer 35

the mitochondrial matrix

Question 36

in animals, where does FA oxidation take place

Answer 36

mitochondrial matrix

Question 37

T or F: FAs with 12C or less can cross the mitochondrial membrane unassisted

Answer 37

true

Question 38

T or F: FAs with 14C or more can cross the mitochondrial membrane unassisted

Answer 38

false; they require multiple enzymatic steps to enter the matrix

Question 39

what is the name of the steps required to get 14C+ FAs into the mito matrix in preparation for oxidation

Answer 39

the carnitine shuttle

Question 40

briefly list the 4 basic steps of the carnitine shuttle

Answer 40

FA is esterified to CoA, CoA is swapped for carnitine, FA-carnitine passes both mito membranes, carnitine is re-swapped for CoA

Question 41

describe step 1 of the carnitine shuttle

Answer 41

FA is converted to fatty acyl-CoA via acyl-CoA synthetases on the OMM. Costs 2 ATP equivalents

Question 42

how much ATP (if any) does step 1 of the carnitine shuttle cost

Answer 42

2

Question 43

describe step 2 of the carnitine shuttle starting with fatty acyl-COA

Answer 43

the CoA is exchanged via transesterification for a molecule of carnitine. The FA transiently attaches to the carnitine OH group, catalyzed by carnitine acyltransferase I in the OMM. Carnitine ester can now enter the IMS through large pores, then the matrix through a carnitine transporter on the IMM

Question 44

describe step 3 of the carnitine shuttle

Answer 44

fatty acyl group is transferred from carnitine back to CoA by carnitine acyl transferase II on the inner face of the IMM. Carnitine returns to the cytosol through the same transporter, and now we can do b-oxidation

Question 45

how/where is carnitine synthesized

Answer 45

synthesized from lysine in the liver/kidney/brain or obtained in the diet by red meat and dairy

Question 46

list 3 things that are associated with low carnitine levels

Answer 46

premature infants, diabetics, elderly

Question 47

list 4 things that carnitine supplements have been shown to reduce

Answer 47

hypertension, diabetic ketoacidosis, insulin resistance, cardiac arrhythmias

Question 48

what are the CoA and fatty acyl-CoA stores in the cytoplasm used for

Answer 48

FA biosynthesis and elongation

Question 49

what are the CoA and fatty acyl-CoA stores in the mito matrix used for

Answer 49

FA oxidative degradation

Question 50

what is the commitment step in FA oxidation

Answer 50

conversion of the fatty acyl-CoA to the carnitine ester

Question 51

why does malonyl-Co inhibit carnitine acyltransferase I

Answer 51

we use lots malonyl-CoA for FA synthesis, and it is committed to do so already, so there's nothing else we can do with it, and synthesis and breakdown do NOT happen at the same time. The commitment step of synthesis inhibits the commitment step of degradation

Question 52

what would happen if you have a defective CGI protein

Answer 52

you cannot access DAGs

Question 53

Why would muscle weakness during prolonged exercise be a symptom of a carnitine acyltransferase deficiency?

Answer 53

during prolonged exercise, energy storage is from FAs (not glycogen anymore), so FAs are undergoing oxidation.

Question 54

Patients with a carnitine acyltransferase deficiency still can have some beta oxidation of fatty acids during exercise...how?

Answer 54

fatty acids that are long have to go through the whole pathway we covered, but smaller FAs don’t need to do that and can go right to the mitochondria