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Biochemistry 440: Lectures 22 & 23 - Fatty Acid Catabolism and Ketone Bodies - Prof. Rache, Study notes of Biochemistry

University of Washington (UW) - SeattleBiochemistry
Prof. Rachel Klevit

Information on the catabolism of fatty acids and the production of ketone bodies during starvation conditions. It covers the structure and hydrolysis of fats, the oxidation of saturated and unsaturated fatty acids, and the challenges in oxidizing unsaturated and odd-chain fatty acids. The document also discusses the role of acetyl-coa, coa-sh, and various enzymes such as lipases, hydratases, dehydrogenases, and isomerases in the process.

Typology: Study notes

Pre 2010

Uploaded on 03/18/2009

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Biochemistry 440, Fall, 2008 Lectures 22&23
1
Fatty Acid Catabolism
and Ketone Bodies
Reading assgnment:
Chapter 17.1 and 17.2; p. 647-660 (661-665 optional)
Chapter 17.3; p. 666-667
Lectures 22 & 23
2
Lectures 22&23
Fats are a major source of
stored energy
Stored metabolic fuel in a 70 kg person
Constituent Dry weight (g) Energy (kJ)
Fat 15,000 570,000
Protein 6,000 102,000
Glycogen 225 3,600
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Download Biochemistry 440: Lectures 22 & 23 - Fatty Acid Catabolism and Ketone Bodies - Prof. Rache and more Study notes Biochemistry in PDF only on Docsity!

Fatty Acid Catabolism

and Ketone Bodies

Reading assgnment:

Chapter 17.1 and 17.2; p. 647-660 (661-665 optional)

Chapter 17.3; p. 666-

Lectures 22 & 23

Lectures 22&

Fats are a major source of

stored energy

Stored metabolic fuel in a 70 kg person

Constituent Dry weight (g) Energy (kJ)

Fat 15,000 570,

Protein 6,000 102,

Glycogen 225 3,

Lectures 22&

Structure and hydrolysis of fats

H 2

C C

HC O

O

C

O

O

H 2 C O C

O

lipases

O C

O

fatty acids

H 2 C

HC OH

OH

H

2

C OH

glycerol

Fats are triacylglycerols:

DHAP

gluconeo

genesis

glycolysis

Lectures 22&

Oxidation of fatty acids

 Fatty acid activation

 Transport across the mitochondrial

membrane

 β-oxidation in the mitochondrial matrix

Stages of fatty

acid oxidation

Acetyl-CoA

e

e-

e

Figure 17-

β-oxidation

of saturated

fatty acids

FAD

FADH

H

O

Fatty acyl CoA

Acetyl CoA

H

C C

O

SCoA

CoA-SH

C

O

SCoA

C

O

SCoA

trans - Δ

2

satd.

C

O

SCoA

OH

C

O

SCoA

O

C

O

SCoA

NAD

NADH + H

12C

10C

Lectures 22&

β-oxidation of unsaturated fatty acids

Challenges:

Not an intermediate in saturated fatty acid oxidation

because:

=> Double bond is cis => Not a substrate for hydratase

(can only act on trans )

cis - Δ

C

O

SCoA

Double bond starts at uneven carbon:

Lectures 22&

β-oxidation of unsaturated fatty acids

Steps 2-4 of

β-oxidation

Acetyl-CoA

cis - Δ

C

O

SCoA

trans - Δ

C

O

SCoA

2

3

C

O

SCoA

10 saturated

isomerase

=> Cis-trans isomerization step, then resume β-oxidation at step 2

regular β-

oxidation

Lectures 22&

β-oxidation of poly-unsaturated

fatty acids

 β-oxidation as far as possible

 then apply “strategy” for either cis - Δ

or cis - Δ

Lectures 22&

β-oxidation of odd-chain fatty acids.

C

O

SCoA

H 2

C

C

H

H 2

C

H

C

C

O

SCoA

H

C

H 3 C

Propionyl CoA

C

O

SCoA

H

C

Acetyl CoA

Steps 1-4 of

β-oxidation

Propionyl-CoA -> Succinyl-CoA

SCoA

C

C

O

H

C C

O

H

H

H

O

L-Methylmalonyl CoA

Succinyl CoA

Propionyl CoA

carboxylase

Methylmalonyl-CoA

epimerase

ATP + HCO

3

Methylmalonyl-CoA

mutase

CoAS

C

C

O

H

C C

O

H O

H

H

CoAS

C

C

O

H

C C

O

H O

H

H

C C C

SCoA

O

H

H

H

H

H

ADP + P

i

D-Methylmalonyl CoA

Citric acid

cycle

Yield from fatty

acid oxidation

Acetyl-CoA

e

e-

e

Figure 17-

e.g. hexadecanoic aid

(palmitoic acid, 16C,

fully saturated):

Palmitoyl-CoA + 7CoA + 7FAD + 7NAD

  • 7H 2

O

--> 8 acetyl-CoA + 7FADH 2

+ 7NADH + 7H