Lipid Metabolism

Front 1

A hydrophobic storage lipid.

Back 1

Triacylglycerol

Front 2

Phospholipids, sphingolipids, glycolipids and cholesterol are _________ ________ ________.

Back 2

amphipathic membrane consituents

Front 3

Triacylglycerol's structure includes a ______ backbone ______ with three ________.

Back 3

glycerol backbone
esterified
3 fatty acids

Front 4

FA and glucose belong to ____ carbon pools. Glucose can form the ________ in TAG while FAs can form the _______ part of a TAG. The pools are also linked in that _________ can be made into acetyl-CoA.

Back 4

separate

glycerol

triacyl (fatty acids)

pyruvate

Front 5

Digestion of TAGS

3 steps

Back 5

1)Gastric lipase
2)solubilization by bile acids
3)pancreatic lipase degrades solubilized TAG

Front 6

This degrades TAG but has limited effect because fat is not yet emulsified in the stomach - TAG passes through largely unaltered.

Back 6

Gastric lipase

Front 7

These solubilize TAG and are secreted from the liver/gall bladder.

Back 7

Bile acids

Front 8

Bile acids act rapidly as detergents because they have _____ _______.

Back 8

high CMC - critical micellar concentration

Front 9

This degrades solubilized TAG and is secreted into the duodenum.

Back 9

Pancreatic lipase

Front 10

What is CMC?
What does it mean?

Back 10

Critical micellar concentration: the concentration of detergent monomers in equilibrium with micelles

-determines the speed of solubilization (high = faster)

Front 11

What does enzymatic hydrolysis of TAG yield? (In order.)

Back 11

fatty acids and diacylglycerol, monoacylglycerol, free glycerol

Front 12

Free fatty acids are ______ and help to solubilize _____ TAG.

Back 12

detergents

undigested TAG

Front 13

These package fats for transport to the peripheral organs. They are released from the _____ into the _______ through the thoracic duct, bypassing the _______.

Back 13

Chylomicrons

intestines

lymphatics

liver

Front 14

Lipid droplets with a hydrophilic protein coat.

They transport lipids.

Back 14

Lipoproteins

Front 15

Moves TAG and some other lipids from liver to periphery.

Back 15

VLDL

Front 16

Moves lipids, particularly cholesterol, from the liver to the periphery.

Back 16

LDL

Front 17

Moves excess cholesterol from peripheral organs to the liver.

Back 17

HDL

Front 18

These are bound to albumin in the major transport mechanism for release of fat from adipose tissue.

Back 18

Free fatty acids

Front 19

Once a fatty acid is bound to CoA, it is transported into the mitochondrion. During transport, CoA is transiently replaced by ________.

Back 19

carnitine

(so instead of acyl-CoA, acyl-carnitine enters the mitochonrion)

Front 20

Fatty acid synthesis occurs in the ______. It uses ________, a large multi-enzyme complex. The redox cosubstrate involved is _____. Is it reversible? Why?

Back 20

cytosol

fatty acid synthase

NADPH + H+

It's not reversible becase there is no beta-oxidation in the cytosol.

Front 21

Beta oxidation occurs in the _____. It uses a set of separate enzymes. It uses ____________ as redox cosubstrates. Is it reversible? Why?

Back 21

mitochondrion

NAD+ and FAD

It IS reversible - mitochondria can synthesize their own fatty acids by reversed beta-oxidation.

Front 22

Acetyl-CoA can't cross from the mitochondria into the cytosol. How is it transported?

Back 22

1)conversion to citrate
2) conversion to acetoacetate

Front 23

Fatty acid synthase has _____ active sites. All active sites are on _______, and ____ chains are needed to be active. The enzyme only has activity in a _______ state. Thus the activation depends on ___________ and ______ control.

Back 23

multiple active sites

all active sites are on one single polypeptide chain, but 2 (a dimer) or chains are needed to be active

polymeric state

protein phosphorylation, hormonal control

Front 24

FA synthesis by mammalian fatty acid synthase only proceeds to ______. _______ and _______ occur in the endoplasmic reticulum.

Back 24

FA synth. stops at palmitate (Hexadecanoate)

elongation and desaturation occur in the ER

Front 25

The ________ group occurs in both FA synthase and coenzyme A.

Back 25

phosphopantetheine

Front 26

This is an irreversible inhibitor of fatty acid synthase.

Back 26

Cerulenin

Front 27

In a fasting state, where are VLDLs used?
Free fatty acids?
HDL?
IDL & LDLs?

Back 27

VLDLs used by heart and muscle

Free fatty acids used by heart and muscle, replenished by fats from adipose tissue

The other lipoproteins cycle back to the liver.

Front 28

Activated of fatty acids requires _____ ATP equivalents per fatty acid molecule. Activated fatty acids are linked to ___.

Back 28

2

CoA

Front 29

________ transports activated fatty acids into the mitochondrial matrix.

Back 29

Carnitine

Front 30

For every 2 atoms cut off the fatty acyl-CoA, ____ ATP will eventually be generated, for a net of ___ ATP.

Back 30

17

15

2 from QH2, 3 from NADH + H+, 12 from the acetyl-CoA

Front 31

How you you calculate the energy yield of complete oxidation of a saturated fatty acid with n carbons?

Back 31

17 ATP from each round of beta oxidation = (n/2 -1) x 17

12 from the final acetyl-CoA

-2 for activation

Front 32

What role does enoyl-CoA isomerase play in fatty acid metabolism?

What about reductase?

Back 32

It converts cis 3-4 double bond to trans 2-3 bonds.

Unsaturated fatty acids need this conversion when you have CoA-S-C=O next to CH2-C=C. This costs 2 ATP.

Reductase reduces a dienoyl group:

CoA-S-C=O -C=C-C=C ....

Then enoyl-CoA isomerase can act on the product.

This costs 1 NADPH (3 ATP equivalents)

Even numbered dble bonds cost 3 ATP, odd cost 2.

Front 33

How do you calculate the energy yield for unsaturated fatty acids?

Back 33

Double bonds at odd-numbered positions cost 2 ATP

Dble bonds at even positions cost 3 ATP

(# rounds x 17) + 12 -2 - cost of double bonds.

Front 34

How do you calculate the energy yield for complete oxidation of an odd-chain saturated fatty acid?

Back 34

8 + the energy yield for a fatty acid with one less carbon.

(n/2 - 1)17 +12 -2 +8

Front 35

What is proprionyl-CoA? What is done with it?

Back 35

What you get at the end of complete oxidation of odd-chain fatty acids (3 C, not 2)

proprionyl-CoA carboxylase adds -COO to the alpha carbon

Methylmalonyl-CoA epimerase & mutase moves the carboxyl to the terminal C, making succinyl-CoA which then enters the TCA. Can take the malate, turn into pyruvate with malic acid.

Front 36

Where does oxidation of very long fatty acids occur?

What is the energy yield for each round?

Is the oxidation complete?

Back 36

Peroxisomes

15 (2 less than in mitochondria)

No - once there are less than 22 carbons the chain enters the mitochondria via carnitine as usual - peroxisomes have low affinity for short chains

Front 37

What are the key differences between beta-oxidation and oxidation of very long fatty acids?

Back 37

peroxisomes vs. mitochondria

22+ carbon atoms

instead of producing ubiquinone in the first step hydrogen peroxide is produced so each round yields 2 less ATP than beta-oxidation

Front 38

What coenzyme is used in fatty acid synthesis?

Back 38

ACP - acyl carrier protein

instead of CoA - all the enzymes are the same

acetyl-CoA carboxylase makes malonyl-CoA to add to the transacylated acetyl-ACP

the next intermediate slips the malonyl's acyl group between the ACP-S and its acetyl

Front 39

Where does fatty acid synthesis occur?

Back 39

cytosol

Front 40

What is the difference between electron carriers between fatty acid synth and beta oxidation?

Back 40

fatty acyl-CoA uses FADH2 to reduce Q

fatty acyl-ACP oxidized NADPH + H+ to NADP+