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Fat Metabolism
I’m not fat, I’ve just got a lot of potential energy!
Digestion, Mobilization, and
Transport
•
http://courses.cm.utexas.edu/emarcotte/ch339k/fall2005/Lecture-Ch17-1/Slide2.JPG
Emulsification
• Fats are not water soluble
• Made into bile salts that are
• Absorbed as micelles in small intestines
Chylomicron Carriers
• proteins that carry fats
• stored in adipose tissue
Role of Hormones
• Can mobilize from adipose
• Release as Fatty acids
• Epinephrene and glucagon release cAMP
– make fatty acids and glycerol
– mobilizes fat
Animation of Process
• http://www.wiley.com/legacy/college/boyer/
0470003790/animations/fatty_acid_metabol
ism/fatty_acid_metabolism.htm
• FUN!
Activation and Transported to
Mitochondria
• FA + CoASH --> ATP = FA-SCoA + AMP
+ Ppi
• Driven by breakup of Ppi
• Acyl CoA Synthetase
• -32.5 kJ
• Transported through inner mitochondrial
membrane via carnitine
– uses specific acyl carnitine transporter
Carnitine
CH3
H3C
O
+
N CH2 CH CH2 C
CH3
OH
O
Formation of acyl carnitine
CH3
H3C
N CH2 CH CH2 C
CH3
carnitine
OH
O
CH3
O
O
+
+
CoAS C
R
H3C
CH3
acyl CoA
O
+
N CH2 CH CH2 C
O
+
O
C
O
R
acyl carnitine
• Can get transported across inner mitochondrial
membrane
CoASH
Animation of Process
• http://www.brookscole.com/chemistry_d/te
mplates/student_resources/shared_resources
/animations/carnitine/carnitine1.html
Beta Oxidation
• Breakdown of fats into
– Acetyl coenzyme A --> Krebs Cycle
– FADH2 --> Oxidative Phosphorylation
– NADH--> Oxidative Phosphorylation
• Breaks off two carbons at a time to acetyl
CoA
– Remaining goes another round
Reactions Diagram
acetyl CoA
O
O
O
acyl-CoA
R
CH2
CH2
CH2
C
S-CoA
R
CH2
C
CH3
S-CoA
C
S-CoA
FAD
Acyl-CoA Dehydrogenase
FADH2
HSCoA
thiolase
O
beta-enoyl CoA
O
O
R
CH
CH
CH2
C
S-CoA
R
CH2
C
CH2
beta-ketoacyl CoA
H2O
enoyl-CoA hydratase
beta-hydroxyacyl-CoA
dehydrogenase
O
OH
R
CH2
CH
CH2
C
NADH
NAD+
S-CoA
beta hydroxyacyl CoA
C
S-CoA
Reactions of Beta Oxidation
Acyl-CoA Dehydrogenase
FAD
O
R
CH2
CH2
CH2
C
FADH2
O
R
S-CoA
CH
CH
CH2
Acyl-CoA Dehydrogenase
acyl-CoA
beta-enoyl CoA
– Puts in a ß double bond
• Oxidizes C-C bond to double bond
– Produces FADH2
C
S-CoA
Reactions of Beta oxidation
Enoyl CoA Hydratase
H2O
OH
O
R
CH
CH
CH2
C
R
S-CoA
CH2
CH
O
CH2
enoyl-CoA hydratase
beta-enoyl CoA
• adds water
– forms ß-hydroxy product
beta-hydroxyacyl CoA
C
S-CoA
Reactions of Beta Oxidation
ß-hydroxylacyl-CoA dehydrogenase
OH
R
CH2
CH
NAD+
O
CH2
C
NADH
R
S-CoA
O
O
CH2
C
CH2
C
beta-hydroxyacyl-CoA
beta-hydroxyacyl CoA
dehydrogenase
• oxidizes secondary alcohol to ketone
– Oxygen-containing group
– Produces NADH
beta-ketoacyl CoA
S-CoA
Reactions of Beta Oxidation
Acyl-CoA acetyltransferase (thiolase)
O
acetyl CoA
O
O
CH3
C
S-CoA
HSCoA
R
CH2
C
CH2
C
S-CoA
O
beta-ketoacyl CoA
R
CH2
C
thiolase
acyl CoA
• Uses another CoA
• Produces Acetyl CoA
• Acyl CoA can go another round
S-CoA
Overall Per Beta Oxidation cycle
• 1 FADH2…………………………1.5 ATP
• 1 NADH………………………….2.5 ATP
• 1 Acetyl CoA to Krebs
– 3 NADH X 2.5 ATP / NADH………7.5 ATP
– 1 FADH2…………………………….1.5 ATP
– 1 GTP………………………………..1.0 ATP
Total =
14.0 ATP
Beta Oxidation on 16 C fatty Acid
O
CH3 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 C
O
Beta Oxidation on 16 C fatty Acid
2
1
3
4
6
5
8
7
O
CH3 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 C
7
6
O
3
5
4
2
1
• 7 rounds of Beta oxidation (bottom numbers)
• Form 8 acetyl Co A (top numbers)
Beta Oxidation on 16 C fatty Acid
totals
•
7 rounds of beta oxidation
7 rounds X FADH2 X 1.5 ATP
round
FADH2
7 rounds X NADH X 2.5 ATP
round
NADH
8 acetyl CoA
8 Krebs
8 Krebs X 3 NADH X 2.5 ATP
Krebs
NADH
8 Krebs X FADH2 X 1.5 ATP
Krebs
FADH2
8 Krebs X GTP
X 1 ATP
Krebs
GTP
1 ATP used to activate
Total
=
10.5 ATP
= 17.5 ATP
= 60 ATP
= 12 ATP
=
8 ATP
= - 1 ATP
107 ATP
Unsaturated Fat Metabolism
• special enzymes needed to convert cis
bonds in fatty acids to trans bonds
Regulation of Fat Metabolism
• Transport is rate-limiting
• Regulation of carnitine acyl transferase
– off by fat synth products
– high NADH
Ketone Bodies
• Starvation causes accumulation of acetyl
CoA
– not enough carbohydrates to keep Kreb’s Cycle
going
– acetyl CoA forms acetoacetate, bhydroxybutyrate, and acetone.
• http://www.biocarta.com/pathfiles/ketonebo
diesPathway.asp
Diabetes and Ketone Bodies
• When there is not enough insulin in the blood and
it must break down fat for its energy.
• Ketones build up in the blood and then spill over
into the urine so that the body can get rid of them.
Acetone can be exhaled through the lungs. This
gives the breath a fruity odor. Ketones that build
up in the body for a long time lead to serious
illness and coma. (Diabetic ketoacidosis)
Comparison of Fat Metabolism per
gram and CHO per gram
• Fats provide about 9 kilocalories per gram
and carbohydrates provide about 4
kilocalories per gram.
• Using nutritional units, that is 9
Calories/gram for fats and 4 Calories/gram
for carbohydrates.
• CHO provide energy more quickly
• Fats are good fuel for endurance events, but
not sprints