Chapter 22: Fatty Acids

Front 1

a fatty acid with a double bond is labeled...
a fatty acid with 2 double bonds is labeled...

Back 1

-enoic acid
-dienoic acid

Front 2

an omega 3 fatty acid has a double bond where?

Back 2

3 from end (not carboxyl end)

Front 3

4 major roles of fatty acids

Back 3

1) fuel molecules (stored as triacylglycerols)
2) building blocks of phospholipids and glycolipids
3) anchors for membrane and associated proteins
4) hormones and second messengers

Front 4

triacylglycerols

Back 4

"fat": uncharged esters of fatty acids with glycerol

Front 5

3 types of hormones and second messengers that use fatty acids

Back 5

steroid hormones, prostaglandins, diacylglycerols (intracellular second messengers)

Front 6

fatty acids are derived from 2 sources:

Back 6

dietary fat and triacylglyceride storage

Front 7

lipases

Back 7

-synthesized in pancreas
-degrade dietary fats in intestines to fatty acids and monoacylglycerol for absorption into intestine
-lipids aren't water soluble though, so they must be made accessible to lipases by bile salts

Front 8

bile salts

Back 8

-derived from cholesterol
-suspend lipids by packaging into micelles
-amphipathic molecules so can emulsify lipids (no charge in fats, but there is in f.a.s)

Front 9

chylomicrons

Back 9

lipoprotein transport particles--deliver triacylglycerides to membrane-associated lipases mostly in adipose and muscle tissue

Front 10

after lipases degrade lipids to fatty acids and monoacylglycerol...

Back 10

triacylglycerols are re-synthesized in intestinal mucosal cells and packaged into chylomicrons

Front 11

triacylglycerides (stored fats) are processed in 3 stages:

Back 11

1) mobilization from adipose storage (degraded to f.a.'s and glycerol, released and transported)
2) processing in target tissues and cells (activation of f.a.s and transport into mitochondria)
3) energy generation in mitochondria (degradation of f.a.s into acetyl CoA and production of FADH2 and NADH)

Front 12

serum albumin

Back 12

carrier of fatty acids in blood

Front 13

triacylglycerol lipase

Back 13

-key hormonal regulatory point in degradation of lipolysis
-epinephrine and glucagon induce lipolysis (activate cAMP-->PKA-->triacylglycerol lipase)
-removes 1 fatty acid at a time from triacylglycerol

Front 14

fate of glycerol after lipolysis

Back 14

glycerol kinase and glycerol phosphate dehydrogenase convert it to DHAP and GAP--can enter gluconeogenesis or glycolysis

Front 15

fatty acid activation for degradation

Back 15

-activated by addition of CoA on outer mitochondrial membrane
-2 step conversion of fatty acid to acyl CoA uses acyl CoA synthetase and requires ATP

Front 16

acyl CoA

Back 16

-activated fatty acid
-must be transported across inner mitochondrial membrane because fatty acid oxidation occurs in matrix of mitochondria
-conjugated to carnitine for transport across membrane

Front 17

carnitine

Back 17

-zwitterionic alcohol used to transport acyl CoA across inner mitochondrial membrane
-acyl CoA is conjugated to carnitine to make acyl carnitine by carnitine acyltransferase I, it passes through transclocase, and is converted back to acyl CoA by carnitine acyltransferase II
(maintains high energy transfer potential of acyl CoA)

Front 18

beta-oxidation pathway

Back 18

-takes place in mitochondrial matrix
-one round yields acetyl CoA, a fatty acyl CoA n-2, FADH2 and NADH (from which energy is derived)

Front 19

4 steps in each round of beta-oxidation

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1) oxidation by acyl CoA dehydrogenase
2) hydration by enoyl CoA hydratase
3) oxidation by L-3-hydroxyacyl CoA dehydrogenase
4) thiolysis by beta-ketothiolase

Front 20

oxidation of acyl CoA

Back 20

-forms trans dbl bond between C2 and C3
-first source of ATP (~1.5)
-enzyme is acyl CoA dehydrogenase (several isoforms of this enzyme for different chain lengths)
-FAD is enzyme bound electron acceptor (electrons in FADH2 are transferred to ubiquinone in 3 steps then to cytochrome reductase)

Front 21

acyl CoA DH step of fatty acid degradation (what happens to electrons)

Back 21

1) electrons from FADH2 prosthetic group of reduced acyl CoA are trasferred to 2nd flavoprotein: electron-transferring flavoprotein
2) ETF donates electrons to ETF:ubiquinone reductase (iron-sulfur protein)
3) ubiquinone is reduced to ubiquinol--delivers high potential electrons to 2nd proton-pumping site of respiratory chain

Front 22

step 2 of beta-oxidation

Back 22

-hydration of dbl bond between C2 and C3
-enzyme is enoyl CoA hydratase (one size fits all)
-yields no energy

Front 23

step 3 of beta-oxidation

Back 23

-second oxidation reaction--conversion of hydroxyl at C3 into a keto group
-enzyme: L-3-hydroxyacyl CoA dehydrogenase (one size fits all, stereospecific)
-yields 2.5 ATP from reduction of NAD

Front 24

step 4 of beta-oxidation

Back 24

-cleavage of 3-ketoacyl CoA by thiol group of coenzymeA
-enzyme: beta-ketothiolase
-yields acyl CoA (-2 C atoms) and acetyl CoA (latter can go into TCA cycle to yield ~10ATP)

Front 25

oxidation of plamitate yields

Back 25

about 106 ATP (goes through 7 rounds of beta-oxidation)

Front 26

peroxisome and fatty acids

Back 26

can oxidize fatty acids but by different process: first step uses flavoprotein oxidase instead of dehydrogenase and produces H202 instead of reducing ETF

Front 27

oxidation of unsaturate fatty acids

Back 27

requires 2 additional enzymes
-odd-numbered dbl bonds: isomerase can fix
-even-numbered dbl bonds: reductase + isomerase

Front 28

if you have an odd number of C atoms in a fatty acid...

Back 28

(rare)
-in final round propionyl CoA and acetyl CoA are produced (instead of 2 acetyl CoA)
-propionyl CoA is converted to succinyl CoA so can enter TCA cycle
-rearrangement requires vit. B12

Front 29

coenzyme B12 structure

Back 29

corrin ring with cobalt in middle--group coming off cobalt toward you is the active part--gives away what it is:
cyanocobalamin: CN
methylcobalamin: CH3
coenzyme B12: looks like nucleic acid

Front 30

methyl malonyl CoA mutase

Back 30

-last step in conversion of propionyl CoA to succinyl CoA--unique reaction involving free radical because of Co
-homolytic cleavage: electron stays with Co and one electron stay with the C atom to generate free radical

Front 31

if fatty acid oxidation exceeds capacity of TCA cycle, acetyl CoA...

Back 31

is diverted to form ketone bodies in the liver
conditions leading to formation of ketone bodies: prolonged fasting, high fat/low carb, diabetes

Front 32

3 major ketone bodies

Back 32

-acetoacetate--can be converted to acetone (no ketone group) or D-3-hydroxybutyrate (by oxidation of NADH)

Front 33

3 things about ketone bodies as energy

Back 33

-heart muscle and renal cortex prefer acetoacetate to glucose
-brain normally uses glucose but in starvation or diabetes may adapt to using ketone bodies
-liver produces ketone bodies but can't use them (doesn't have CoA transferase)

Front 34

how ketone bodies are transformed into energy

Back 34

acetoacetate <-CoA transferase-> acetoacetyl CoA <-thiolase-> 2 acetyl CoA
(CoA is transferred from succinyl CoA to acetoacetate)

Front 35

differences between fatty acid synthesis and degradation

Back 35

-degradation takes place in mitochondria, synth takes place in cytoplasm
-intermediates in degradation are covalently attached to CoA, synth=acyl carrier protein
-oxidants in degradation: NAD+, FAD, reductant in synth: NADPH
-chain is degraded 2 Cs at a time, split off as 2-C acetyl CoA, chain grows by 2 C's at a time, donated by 3-C malonyl CoA

Front 36

committed step in fatty acid synthesis is...

Back 36

formation of malonyl CoA (2C donor in subsequent synthesis) by acetyl CoA carboxylase
converts acetyl CoA to malonyl CoA

Front 37

3 enzymes that use biotin

Back 37

pyruvate carboxylase, propionyl CoA carboxylase, acetyl CoA carboxylase

Front 38

regulation of acetyl CoA carboxylase

Back 38

-glucagon and epinephrine promote inactivation, insulin promotes activation (not clear how)
-AMP-activated protein kinase phosphorylates carboxylase (inactivates it) when [AMP] is high; protein phosphatase 2A dephosphorylates carboxylase (activates it)
-citrate activates carboxylase by converting enzyme from inactive dimer to filamentous active form; Palmitoyl CoA (abundant when there is excess of f.a.s does opposite)

Front 39

malonyl CoA inhibits

Back 39

carnitine acyltransferase I--prevents conjugation of acyl CoA to carnitine, so can't get into mitochondria to undergo beta-oxidation in times of plenty

Front 40

CoA and acyl carrier protein

Back 40

different carriers, same business end (phosphopantetheine group)

Front 41

steps of fatty acid synthesis

Back 41

1) acetyla CoA is converted to malonyl CoA (regulatory step)
2) acetyl CoA and malonyl CoA are converted to acetyl ACP and malonyl ACP
3) acetyl ACP (2C) and malonyl ACP (3C) are condensed to acetoacetyl ACP (4C)
4) reduction with NADPH
5) dehydration
6) reduction with NADPH to butyryl ACP

Front 42

synthesis of even vs. odd numbered fatty acids

Back 42

even numbered are derived from acetyl CoA
odd-numbered start with propionyl CoA

Front 43

fatty acid synthase

Back 43

7 catalytic activities on one polypeptide chain
-has 3 domains
-fatty acid chain gets passed around until it reaches length of C16

Front 44

domain 1 of fatty acid synthase

Back 44

-contains acetyl transferase, malonyl transferase, condensing enzyme
-substrate entry and condensation

Front 45

domain 2 of fatty acid synthase

Back 45

-contains ACP, beta-ketoacyl reductase, dehydratase, enoyl reductase
-responsible for reduction

Front 46

domain 3 of fatty acid synthase

Back 46

-contains thioesterase
-release of C16-ACP

Front 47

what carries the fatty acid chain from one catalytic site to next?

Back 47

phosphopantetheinyl group of ACP

Front 48

modification of fatty acids

Back 48

-takes place in ER
-elongation: resembles fatty acid synthesis but fatty acyl chain is attached to CoA not ACP
-desaturation: introduction of double bonds

Front 49

essential fatty acids

Back 49

linoleate and linolenate (mammals lack enzyme to introduce double bonds at carbon atoms beyond C-9 in fatty acid chain)

Front 50

transport of acetyl CoA across mitochondrial membrane

Back 50

-acetyl CoA is synthesized in mitochondria, but f.a. synthesis uses it in cytosol
-citrate carries acetyl groups across mito membrane
-for each acetyl CoA transported, one NADPH is generated
-carnitine can also transport acetyl CoA but only long chains

Front 51

antibacterial agents and fatty acid synthesis

Back 51

triclosan, isoniazid inhibit enoyl ACP reductase (step from crotonyl ACP to butyryl ACP--last reduction step)

Front 52

arachidonate

Back 52

(20:4), derived from linoleate, precursor for several classes of signaling molecules

Front 53

eicosanoids

Back 53

important fatty acid derivatives with specialized functions; arachidonic acid is precursor

Front 54

NSAIDs

Back 54

inhibit prostaglandin synthesis by blocking cyclooxygenase activity of prostaglandin synthase