Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

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Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

Transcript of Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

Page 1: Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

Fat Metabolism

I’m not fat, I’ve just got a lot of potential energy!

Page 2: 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

Page 3: Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

Emulsification

• Fats are not water soluble

• Made into bile salts that are

• Absorbed as micelles in small intestines

Page 4: Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

Chylomicron Carriers

• proteins that carry fats

• stored in adipose tissue

Page 5: Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

Role of Hormones

• Can mobilize from adipose

• Release as Fatty acids

• Epinephrene and glucagon release cAMP– make fatty acids and glycerol– mobilizes fat

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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

Page 8: Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

Carnitine

N+

CH2CH3

CH3

CH3

CH CH2

OH

CO

O

Page 9: Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

Formation of acyl carnitine

N+

CH2CH3

CH3

CH3

CH CH2

OH

CO

OCoAS C R

O

carnitine acyl CoA

N+

CH2CH3

CH3

CH3

CH CH2

O

CO

O

C

R

O

CoASH

acyl carnitine

+ +

• Can get transported across inner mitochondrial membrane

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Animation of Process

• http://www.brookscole.com/chemistry_d/templates/student_resources/shared_resources/animations/carnitine/carnitine1.html

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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

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Reactions DiagramCH2R CH2 CH2 C

O

S-CoA

FAD

FADH2

CHR CH CH2 C

O

S-CoA

Acyl-CoA Dehydrogenase

acyl-CoA

beta-enoyl CoA

OH2

enoyl-CoA hydratase

NAD+

NADHbeta-hydroxyacyl-CoA

dehydrogenase

CH2R C CH2 C

O

S-CoA

O

thiolaseHSCoA

CH3 C

O

S-CoA

beta-ketoacyl CoA

acetyl CoA

CH2 C

O

S-CoAR

CH2R CH CH2 C

O

S-CoA

OH

beta hydroxyacyl CoA

Page 13: Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

Reactions of Beta Oxidation Acyl-CoA Dehydrogenase

CH2R CH2 CH2 C

O

S-CoA

FAD FADH2

Acyl-CoA Dehydrogenase

acyl-CoA beta-enoyl CoA

CHR CH CH2 C S-CoA

O

– Puts in a ß double bond• Oxidizes C-C bond to double bond

– Produces FADH2

Page 14: Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

Reactions of Beta oxidationEnoyl CoA Hydratase

CHR CH CH2 C

O

S-CoA

beta-enoyl CoA

OH2

enoyl-CoA hydratase

CH2R CH CH2 C

O

S-CoA

OH

beta-hydroxyacyl CoA

• adds water– forms ß-hydroxy product

Page 15: Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

Reactions of Beta Oxidation ß-hydroxylacyl-CoA dehydrogenase

CH2R CH CH2 C

O

S-CoA

OH

beta-hydroxyacyl CoA

NAD+ NADH

beta-hydroxyacyl-CoAdehydrogenase

CH2R C CH2 C

O

S-CoA

O

beta-ketoacyl CoA

• oxidizes secondary alcohol to ketone– Oxygen-containing group

– Produces NADH

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Reactions of Beta Oxidation Acyl-CoA acetyltransferase (thiolase)

CH2R C CH2 C

O

S-CoA

O

thiolase

HSCoA

CH3 C

O

S-CoA

beta-ketoacyl CoA

acetyl CoA

CH2 C

O

S-CoAR

acyl CoA

• Uses another CoA• Produces Acetyl CoA• Acyl CoA can go another round

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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

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Beta Oxidation on 16 C fatty Acid

CH2 CO

O

CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2

CH2CH3

Page 19: Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

Beta Oxidation on 16 C fatty Acid

CH2 CO

O

CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2

CH2CH3

12

34567

1 2 3 4 5 6 78

• 7 rounds of Beta oxidation (bottom numbers)• Form 8 acetyl Co A (top numbers)

Page 20: Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

Beta Oxidation on 16 C fatty Acidtotals

• 7 rounds of beta oxidation7 rounds X FADH2 X 1.5 ATP = 10.5 ATP

round FADH2

7 rounds X NADH X 2.5 ATP = 17.5 ATP round NADH

8 acetyl CoA8 Krebs

8 Krebs X 3 NADH X 2.5 ATP = 60 ATP Krebs NADH

8 Krebs X FADH2 X 1.5 ATP = 12 ATP Krebs FADH2

8 Krebs X GTP X 1 ATP = 8 ATPKrebs GTP

1 ATP used to activate = - 1 ATP

Total 107 ATP

Page 21: Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

Unsaturated Fat Metabolism

• special enzymes needed to convert cis bonds in fatty acids to trans bonds

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Regulation of Fat Metabolism

• Transport is rate-limiting

• Regulation of carnitine acyl transferase– off by fat synth products– high NADH

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Ketone Bodies

• Starvation causes accumulation of acetyl CoA– not enough carbohydrates to keep Kreb’s Cycle

going– acetyl CoA forms acetoacetate, b-

hydroxybutyrate, and acetone.

• http://www.biocarta.com/pathfiles/ketonebodiesPathway.asp

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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)

Page 25: Fat Metabolism I’m not fat, I’ve just got a lot of potential energy!

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