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Lecture 27 - β-oxidation
Fichas del conjunto (22)
- 1GOALS->Learn sites of β oxidation in cells and four repeating steps involved
->Understand how fatty acids are activated and transported to mitochondria
->Learn how oxidation is connected to the electron transport chain and citric acid cycle, and calculate yield of ATP from the oxidation of a fatty acid
->Know the differences between β oxidation of fatty acids with even and
odd numbers of carbons
->Understand additional steps in the oxidation of unsaturated fatty acids
->Describe the difference between β oxidation and α oxidation - 2TUTORIAL 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)2
carboxylic acid
acetyl COA
ester
thioester - 3β 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 COAmitochondria
Carnitine
carnitine
Acylcarnitine
acyltransferase Il - 4β oxidation: Four steps l. _____ 2. _____ 3. _____ 4. _____ 1st oxidation generates ___ 2nd oxidation generates ___ FADH2 and NADH go to the __ __ __ acetyl COA goes into the __ ___ ___l. oxidation
2. hydration
3. oxidation
4. thiolysis
FADH2
NADH
electron transport chain
citric acid cycle - 5Fatty 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)2
oxidation, hydration, oxidation, and thiolysis
Beta carbon - 6Why are fatty acids degraded? ->Turnover of membrane lipids ->Yields ___ ->Yield carbons for ___ __ synthesisenergy
amino acid - 7Fatty acid oxidation Primarily occurs in ____. There are two steps: 1.) ____ 2.) ____- Four repeating steps — oxidation, hydration, oxidation and thiolysis, then repeatmitochondria
Activation
Degradation - 8Ester 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 acidsfatty acid
***Most fatty acids are not free, they are incorporated into lipids SO the ester bond must be hydrolyzed (broken) to release the fatty acid
activated
thioester (to become activated)
activation (free fatty acid becomes acyl-CoA via acyl-CoA synthetase) - 9—To make a FA you need to get rid of ketone but to degrade FA you need introduce an acyl group (a ketone) so that once cleaved, a fatty acid will still remain
- 10—1 round yields = 1 acetyl CoA and 1 fatty acyl CoA
LAST round = 2 molecules of acetyl CoA
-so if you have a 16 carbon molecule you go through 7 times to get down to a 4 carbon molecule
You need to get down to the 4 carbon molecule to generate two acetyl CoA
- 11Fatty 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 peroxisomesperoxisomes
mitochondria
α - 12Mitochondrial 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 ___dehydrogenase
reduced
oxidase
H2O2
***Important to reduce FAD in mitochondria because the energy can be transferred to the ETC (cannot do this in the peroxisome) - 13β 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)Eight
2
120
120
1 cycle of oxidation produces 14 ATP and last acetyl CoA produced 10 ATP
-(14 *#of cycles) + 10 ATP = GROSS amount)
-(14 *#of cycles) + 10 ATP - 2ATP = NET amount) - 14Comparison 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 mitochondriaCoA = degradation (β oxidation)
ACP = synthesis (FAS)
2
3
cytoplasm = FAS
mitochondria = β oxidation - 15—
- 16Problem — how to get fatty acids into mitochondria? Little ones (diffuse
carnitine - 17Problem — 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 carnitineCarnitine acyltransferase l
***key to regulation
Acylcarnitine
Carnitine acyltransferase Il - 18—
- 19What 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 cycleeven
β oxidation
propionyl CoA
Propionyl COA
succinyl
**Odd FA chain = stop at 5 carbons and end up with 2 carbons (acetyl CoA) and 3 carbons (propionyl CoA) - 20What 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 resumescis
wrong place
trans
trans-Δ2-Enoyl COA
Isomerase
***Needs to be in TRANSconfiguration
AND double bond needs to be in the right place - 21Fatty 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 ____cannot
α
β
peroxisomes - 22Recap •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 oxidationacylcarnitine
β
acyl COA
acetyl COA
FADH2
NADH
acetyl COA
reduction/isomerization
α