GOALS

TUTORIAL SLIDES

β oxidation:
Degradation of fatty acid removing _ carbons at a time

Proceeds from the ___ __ end of the fatty acid

2 carbons released as I molecule of ___ ___

Fatty acids must be removed from the lipid (break ___)

Fatty acids must be activated (form ____ with COA)

β oxidation occurs in ____ (mostly)

Must get fatty acids into mitochondria first

___ is a carrier for transport

Carnitine acyltransferase I (in CYTOPLASM) transfers acyl group from acyl COA to ____

_____ is translocated into mitochondria, while carnitine is translocated out

Carnitine ____ __
(in mitochondria) transfers acyl group
from acylcarnitine to COA

β oxidation:

Four steps
l. _____
2. _____
3. _____
4. _____

1st oxidation generates ___
2nd oxidation generates ___

FADH2 and NADH go to the __ __ __

acetyl COA goes into the __ ___ ___

Fatty acids are synthesized and degraded by adding or removing _ carbons at a time.

For fatty acid oxidation
Four repeating steps — ___, ___, ____, ___, then repeat

FA's built and degraded at the same carbon! (at the __ carbon)

Why are fatty acids degraded?

->Turnover of membrane lipids

->Yields ___

->Yield carbons for ___ __ synthesis

Fatty acid oxidation

Primarily occurs in ____.

There are two steps:

1.) ____

2.) ____- Four repeating steps — oxidation, hydration, oxidation and thiolysis, then repeat

Ester linkage between fatty acid and carbon backbone of lipid must be hydrolyzed to yield __ ___

Free fatty acids must be ____ before they can be degraded.

Forms a ___ with COA.

This is the same reaction we discussed in lipid synthesis — ___ of fatty acids

Fatty acid oxidation also occurs in
peroxisomes

Very long-chain fatty acids (>C26) are oxidized in _____

When shorter, fatty acids are transported to ___ for further oxidation

__ oxidation also occurs in peroxisomes

Mitochondrial vs peroxisomal oxidation

In mitochondria — first oxidation is catalyzed by acyl-COA ____— FAD is ___

In peroxisomes — first oxidation is catalyzed by acyl-COA ___— electrons transferred to 02 to generate ___

β oxidation and energy

Consider this example — stearate = C18 fatty acid

How many ATP could be made?

___ cycles of β oxidation generate:

8 QH2
12 ATP
8 NADH yields 20 ATP
9 acetyl COA yields 90 ATP

Activation of stearate cost _ ATP equivalents

I molecule of stearate can
yield ___ ATP

Oxidation of stearate = ___ ATP; oxidation of 3 glucose (CI8) = 96 ATP

SHORTCUT??? (for both gross and net ATP)

Comparison of fatty acid synthesis and β
oxidation

Opposite processes but different:

Different cofactors (COA vs ACP)

Oxidation — _ carbon products

Synthesis — __ carbon substrate

Different compartments:
cytoplasm vs mitochondria

Problem — how to get fatty acids into
mitochondria?

Little ones (<C12) = ___

BIGGER ones need transport

Transported with ___ as a carrier

Problem — how to get fatty acids into mitochondria?

1. ___ ___ _ covalently links acyl group from fatty acyl COA to carnitine — occurs at outer membrane of mitochondria

2. ____ is translocated INTO the
mitochondrial matrix as carnitine is translocated OUT of the matrix

3. ___ ____ __ in matrix
of the mitochondria, transfers acyl group to COA, generating acyl COA and free
carnitine

What happens to odd chain fatty acids?

Most ANIMAL fatty acids have ___ number of carbons

Odd chain fatty acids are made by other species

These can be degraded by __ ___

The last step produces 1 molecule of acetyl COA (C2) and I molecule of ___ __ (C3)

__ __ is converted to ___ CoA, which is used in the citric acid cycle

What happens to unsaturated fatty acids?

• β oxidation occurs as normal until double bond gets in the way — occurs because l) double bond may be ___ and may be in the __ __, e.g. Δ3
position, or 2) might be a Δ2'4 diene

l) If an isomerase converts to ___ and moves the double bond to the Δ2
position yielding a ___-___-___ ___ (product of first oxidation step of β
oxidation — remember) and β oxidation resumes

•2) If reductase reduces a double bond, generating a double bond in the wrong
place:
->___ moves the double bond to the Δ2 position yielding a trans-Δ2-Enoyl COA and β oxidation resumes

Fatty acid oxidation via other mechanisms

If β carbon is methylated, e.g. in phytanic acid, β oxidation ___ occur
-> Can be modified by __ oxidation

Resulting product can be degraded by __ oxidation

α oxidation occurs in ____

Recap
•Fatty acids are transported as ___ into the mitochondria, where _ oxidation occurs (transport is KEY regulatory step)

•Oxidation involves 4 repeated steps of: oxidation, hydration, oxidation and
thiolysis to generate __ __ (shorter by 2 C's) and __ ___

•Oxidation steps generate ___ and ___ — connect to electron transport
chain — also generates __ __ which enters citric acid cycle

•UNsaturated fatty acids required additional steps for degradation — either
isomerization or ___/___ to generate a substrate for oxidation enzymes

•BRANCHED (i.e. methylated) fatty acids must undergo _ oxidation (in peroxisome) prior to β oxidation