chapter 17

Question 1

Oxidation of fatty acids is a major energy source in many organisms
-About one-third of our energy needs comes from
-About 80% of energy needs of mammalian heart and liver are met by
-Many hibernating animals, such as grizzly bears, rely almost exclusively on
Some animals (camels) store

Answer 1

-About one-third of our energy needs comes from dietary triacylglycerols
-About 80% of energy needs of mammalian heart and liver are met by oxidation of fatty acids
-Many hibernating animals, such as grizzly bears, rely almost exclusively on fats as their source of energy
-Some animals (camels) store fat as an eventual source of water

Question 2

Fats provide efficient fuel storage
The advantage of fats over polysaccharides:

Answer 2

The advantage of fats over polysaccharides:
-Fatty acids carry more energy per carbon because they are more reduced
-Fatty acids carry less water along because they are nonpolar

-Glucose and glycogen are for short-term energy needs, quick delivery
-Fats are for long-term (months) energy needs, good storage, slow delivery

Question 3

Fat Storage in White Adipose Tissue

Answer 3

Fat stores in cells. (a) Cross section of human white adipose tissue. Each cell contains a fat droplet (white) so large that it squeezes the nucleus (stained red) against the plasma membrane.

Question 4

Lipid Digestion

Answer 4

Dietary fatty acids are absorbed in the vertebrate small intestine
1. Bile emusilfies dietary fats producing mixed micelles
2. turn into signle fatty acids by lipase which degrade triacylglycerols
3. they are converted agin into tiacylglecerols
4. turned into chylomicrons
5. chylomicrons move through the blood stream
6. lipases converts triacylglycerols to fatty acids and glycerol
7. fatty acids are oxidized as fuel for storage

Question 5

Lipids are transported 
in the blood as

Answer 5

chylomicrons

Question 6

Hormones trigger mobilization of stored triacylglycerols

Answer 6

Low glucose trigger the release of glucagon, 1 the hormone binds its receptor and 2 stimulates adenylyl cyclase to produce cAMP, activates PKA, which phosphorylates 3 HSL and 4 perilipin molecules on the surface. Phosphorylation of perilipin causes 5 dissociation of the protein CGI from perilipin. CGI then associates with the enzyme adipose triacylglycerol lipase (ATGL), activating it. Active ATGL 6 converts TAGs to DAGs. The phosphorylated perilipin associates with phosphorylated

HSL allowing it access to the surface, where 7 it converts DAGs to MAGs. A third lipase, MAG lipase (MGL) 8, hydrolyzes MAGs. 9 Fatty acids leave the adipocyte, bind serum albumin; they are released from the albumin and 10 enter a myocyte via a specific fatty acid transporter. 11 FAs are oxidized to CO2, and produce ATP for muscle contraction and other energy-requiring metabolism.

Question 7

Hydrolysis of fats yields fatty acids and glycerol

Answer 7

-Hydrolysis of triacylglycerols is catalyzed by lipases
-Some lipases are regulated by hormones glucagon and epinephrine

Epinephrine means: “We need energy now”
Glucagon means: “We are out of glucose”

Question 8

Glycerol from fats enters glycolysis

Answer 8

Glycerol kinase activates glycerol at the expense of ATP

Subsequent reactions
recover more than enough
ATP to cover this cost

Allows limited anaerobic catabolism of fats

Question 9

Energetics of Glycerol as An Energy Source
Can glycerol be FERMENTED?

Answer 9

NO
-glycerol can only produce 1 pyruvate and has a 1 net ATP compared to 2 net ATP in glucose.

-glycerol can’t be fermented because glycerol can only produce 1 pyruvate without oxygen; net NADH is produced. NADH increases and inhibits enzyme and inhibits glycerol to pyruvate when NADH increases, can inhibit ATP

Question 10

Transport or attachment to phospholipids requires conversion to

Answer 10

-before free fatty acid can be oxidized it must be turned into Acetyl-CoA fatty acid and transported into mitochondria

Overall reaction is fatty acid + CoA + ATP ↔ fatty acyl-CoA + AMP + 2Pi
ΔG’º is -34kJ/mol

Acyl-CoA synthetase reaction

Question 11

Fatty Acid Transport into Mitochondria
-Fats are degraded into fatty acids and glycerol in the
-Fatty acids are transported to
-β-oxidation of fatty acids occurs in
-Small (< ___carbons) fatty acids
-Larger fatty acids (most free fatty acids) are transported via

Answer 11

-Fats are degraded into fatty acids and glycerol in the cytoplasm of adipocytes
-Fatty acids are transported to other tissues for fuel
-β-oxidation of fatty acids occurs in mitochondria
-Small (< 12 carbons) fatty acids diffuse freely across mitochondrial membranes
-Larger fatty acids (most free fatty acids) are transported via acyl-carnitine/carnitine transporter

Question 12

Acyl-Carnitine/Carnitine Transport

Answer 12

Carnitine shuttles fatty acids into the mitochondrial matrix

Question 13

Stages of Fatty Acid Oxidation

Answer 13

-Stage 1 consists of oxidative conversion of two-carbon units into acetyl-CoA via β-oxidation with concomitant generation of NADH and FADH2
involves oxidation of β carbon to thioester of fatty acyl-CoA
-Stage 2 involves oxidation of acetyl-CoA into CO2 via citric acid cycle with concomitant generation NADH and FADH2
-Stage 3 generates ATP from NADH and FADH2 via the respiratory chain

Question 14

The β-Oxidation Pathway

Answer 14

Each pass removes one acetyl moiety in the form of acetyl-CoA.

One round (a) and Further round (b) of β-oxidation

Question 15

Step 1:


Answer 15


Dehydrogenation of Alkane to Alkene

Catalyzed by isoforms of acyl-CoA dehydrogenase (AD) on the inner-mitochondrial membrane
-Very-long-chain AD (12–18 carbons)
-Medium-chain AD (4–14 carbons)
-Short-chain AD (4–8 carbons)

Results in trans double bond, different from naturally occurring unsaturated fatty acids

Analogous to succinate dehydrogenase reaction in the citric acid cycle
-Electrons from bound FAD transferred directly to the electron- transport chain via electron-transferring flavoprotein (ETF)

Question 16

Step 2:


Answer 16

Hydration of Alkene

Catalyzed by two isoforms of enoyl-CoA hydratase:
-Soluble short-chain hydratase (crotonase)
-Membrane-bound long-chain hydratase, part of trifunctional complex

Water adds across the double bond yielding alcohol

Analogous to fumarase reaction in the citric acid cycle
-Same stereospecificity

Question 17

Step 3:


Answer 17

Dehydrogenation of Alcohol

-Catalyzed by β-hydroxyacyl-CoA dehydrogenase
-The enzyme uses NAD cofactor as the hydride acceptor
-Only L-isomers of hydroxyacyl CoA act as substrates
-Analogous to malate dehydrogenase reaction in the citric acid cycle

Question 18

Step 4:


Answer 18

Transfer of Fatty Acid Chain

Catalyzed by acyl-CoA acetyltransferase (thiolase) via covalent mechanism
-The carbonyl carbon in β-ketoacyl-CoA is electrophilic
-Active site thiolate acts as nucleophile and releases acetyl-CoA
-Terminal sulfur in CoA-SH acts as nucleophile and picks up the fatty acid chain from the enzyme

-The net reaction is thiolysis of carbon-carbon bond

Question 19

Trifunctional Protein

Answer 19

Hetero-octamer

Four α subunits
-enoyl-CoA hydratase activity
-β-hydroxyacyl-CoA dehydrogenase activity
-Responsible for binding to membrane

Four β subunits
-long-chain thiolase activity

-May allow substrate channeling
-Associated with inner-mitochondrial membrane
-Processes fatty acid chains with 12 or more carbons
-Shorter chains processed by soluble enzymes in the matrix

Question 20

Fatty Acid Catabolism for Energy

Answer 20

-For palmitic acid (C16)
Repeating the above four-step process six more times (7 total) results in eight molecules of acetyl-CoA
-FADH2 is formed in each cycle (7 total)
-NADH is formed in each cycle (7 total)

-Acetyl-CoA enters citric acid cycle and further oxidizes into CO2
–This makes more GTP, NADH, and FADH2

-Electrons from all FADH2 and NADH enter ETF

Question 21

Each round produces an acetyl-CoA and shortens the chain by two carbons

Answer 21

-Trifunctional protein, a membrane bound multi subunit protein degrades carbon chains till they are down to C12
-When they are 12 or fewer C, 4 soluble enzymes of the mitochondrial matrix do the job

Question 22

Oxidation of Palmitoyl-CoA

Answer 22

-The overall reaction is
-Palmitoyl-CoA + CoA + FAD + NAD+ + H2O → myristoyl –CoA + acetyl-CoA + FADH2 + NADH + H+

-When electrons are donated from FADH2 and NADH, 4 ATP are generated (1.5 from FADH2 and 2.5 from NADH). Water is also generated from transfer of two electrons to oxygen via the reaction NADH + H+ + ½ O2→ NAD+ + H2O
-Palmitoyl is a 16-C, while myristoyl is a 14-C
-Overall reaction to break down the entire 16-C is

Palmitoyl-CoA + 7CoA + 7FAD + 7NAD+ + 7H2O → 8 acetyl-CoA +7 FADH2 + 7 NADH + 7H+
Or Palmitoyl-CoA + 7CoA + 7O2 + 28Pi + 28ADP → 8 acetyl-CoA + 7H2O + 28ATP

Question 23

Complete Oxidation of Palmitoyl-CoA

Answer 23

-Acetyl-CoA can be fed into the TCA cycle and electrons can be transferred down the respiratory chain to form more ATP
-Overall oxidation from TCA and into the respiratory chain is
8 Acetyl-CoA + 16O2 + 80Pi + 80ADP → 8CoA + 16H2O + 80ATP +16 CO2
-Combining the β-oxidation and acetyl-CoA oxidation
Palmitoyl-CoA + 23O2 + 108Pi + 108ADP → CoA + 23H2O + 108ATP +16 CO2

Question 24

NADH and FADH2 serve as sources of

Answer 24

ATP

Assumes 1 NADH = 2.5 ATP, and 1 FADH2 = 1.5 ATP from Respiratory Electron Transport

Question 25

How many total ATP from 16C FA-CoA?

Answer 25

Assumes 1 NADH = 2.5 ATP, and 1 FADH2 = 1.5 ATP from Respiratory Electron Transport

One β-oxidation: 1 FADH2 + 1 NADH = 1.5 ATP + 2.5 ATP = 4 ATP
One acetyl-CoA via TCA: 3 NADH + 1 FADH2 + 1 ATP = 10 ATP

16C-CoA by full oxidization: 7 β-oxidation cycles + 8 acetyl-CoA

       Total ATP: 7 x 4 ATP + 8 x 10 ATP = 28 ATP + 80 ATP = 108 ATP

Question 26

Similar mechanisms introduce carbonyls in other

Answer 26

metabolic pathways

Question 27

Oxidation of Unsaturated Fatty Acids

Answer 27

-Naturally occurring Unsaturated Fatty acids contain cis double bonds
–Are NOT a substrate for enoyl-CoA hydratase

Two additional enzymes are required
-Isomerase: converts cis double bonds starting at -carbon 3 to trans double bonds
-Reductase: reduces cis double bonds not at carbon 3

-Monounsaturated fatty acids require the isomerase
-Polyunsaturated fatty acids require both enzymes

Question 28

Oxidation of Monounsaturated Fatty Acids

Answer 28

Acetyl- CoA is generated till just before the double bond. Because the enoyl-CoA hydratase recognises only trans double bond, need a Δ3, Δ2, -enoyl-CoA isomerase to change the bond from cis to trans

Question 29

Oxidation of Polyunsaturated Fatty Acids

Answer 29

Need two enzymes, an enoyl-CoA isomerase and 2,4-dienoyl-CoA reductase to change the double bonds to trans. Odd numbered double bonds are handled by the isomerase only, even numbered are handled by the reductase and isomerase

Question 30

First double bond requires
Second requires

Answer 30

isomerization
Second requires reduction/isomerization

Question 31

Oxidation of odd-numbered fatty acids
-Most dietary fatty acids are
-Many plants and some marine organisms also synthesize
-Propionyl-CoA forms from β-oxidation of
-Bacterial metabolism in the rumen of ruminants also produces
-Propionyl-CoA is converted to

Answer 31

-Most dietary fatty acids are even-numbered
-Many plants and some marine organisms also synthesize odd-numbered fatty acids
-Propionyl-CoA forms from β-oxidation of odd-numbered fatty acids
-Bacterial metabolism in the rumen of ruminants also produces propionyl-CoA
-Propionyl-CoA is converted to succinyl-CoA that can enter the TCA cycle. One molecule of ATP is converted to ADP to power the reaction

Question 32

Regulation of Fatty Acid 
Synthesis and Breakdown
what inhibits fatty acid oxidation

Answer 32

-malonyl-CoA

Question 33

β-Oxidation in Plants Occurs 
Mainly in

-Mitochondrial acyl-CoA dehydrogenase passes electrons into respiratory chain via electron-transferring
-Peroxisomal/glyoxysomal acyl-CoA dehydrogenase passes electrons directly to molecular

Answer 33

Peroxisomes

-Mitochondrial acyl-CoA dehydrogenase passes electrons into respiratory chain via electron-transferring flavoprotein
–Energy captured as ATP

-Peroxisomal/glyoxysomal acyl-CoA dehydrogenase passes electrons directly to molecular oxygen
–Energy released as heat
–Hydrogen peroxide eliminated by catalase

Question 34

β-Oxidation in Mitochondria vs.
Peroxisomes or
Glyoxysomes

Answer 34

In plants, fatty acid oxidation occurs primarily in peroxisomes in leaf tissue and in glyoxysomes in germinating seeds

Question 35

Acetyl-CoA in the glyoxysome is then converted to

Answer 35

metabolic intermediates

Question 36

ω-Oxidation of Fatty Acids

Answer 36

-In β oxidation, cleavage occurs at the carboxyl end of the fatty acid.
-ω-oxidation starts furthermost away from the carboxylic acid.
-Normally minor
-Occurs in the endoplasmic reticulum of liver and kidney
-Preferred substrate of 10 or 12 carbon atoms

Question 37

α-Oxidation of Fatty Acids

Answer 37

Presence of a methyl group makes β-oxidation impossible

Use α-oxidation to remove the methyl group

Question 38

Ketone Bodies

Answer 38

-Two fates of acetyl-CoA formed from oxidation of FAs in liver:
–Entry of acetyl-CoA into citric acid cycle
–Conversion of acetyl-CoA into ketone bodies (soluble in blood and urine)

-Acetone is exhaled
-Acetoacetate and D-β-hydroxybutyrate are transported to extrahepatic tissues (skeletal and heart muscle, renal cortex, and brain (under starvation condition of glucose)) and converted to acetyl-CoA and oxidized by the TCA cycle

Question 39

Formation of Ketone Bodies

Answer 39

-Entry of acetyl-CoA into citric acid cycle requires oxaloacetate
-When oxaloacetate is depleted, acetyl-CoA is converted into ketone bodies
–Frees Coenzyme A for continued β-oxidation
-The first step is reverse of the last step in the β-oxidation: thiolase reaction joins two acetate units

Question 40

source of ketone bodies

Answer 40

Liver is the source of ketone bodies

-Production of ketone bodies increases during starvation (and diabetes)
-Ketone bodies are released by liver to bloodstream
-Organs other than liver can use ketone bodies as fuels
-High levels of acetoacetate and β-hydroxybutyrate lower blood pH dangerously (acidosis)