Biochem - Lipid Metabolism 1 (beta oxidation)(slides 13-23)

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the first step in beta oxidation is the conversion of the free fatty acid to its __ __

CoA ester

once the fatty acid is converted to its CoA ester, the second step in beta oxidation is the transport into the ___ ___

mitochondrial matrix

once the CoA ester is transported into the mitochondrial matrix, it undergoes a sequence of 4 repetitive steps:

1) dehydrogenation
2) hydration
3) dehydrogenation (a second one)
4) carbon-carbon cleavage (thiolase reaction)

each cycle of the 4 steps in the mitochondrial matrix lops off __ carbon atoms

2

where does the esterification of the free fatty acid with CoA occur?

outer mitochodondrial membrane

what enzyme catalyzes the reaction of a fatty acid to its CoA ester?

Acyl CoA synthetase

acyl CoA synthetase couples with the cleavage of __ to __and ___ in the reaction of fatty acid -> CoA ester

ATP, AMP, pyrophosphate (PPi)

what drives the entire reaction of fatty acid -> CoA ester strongly to the right?

breakdown of pyrophosphate (to inorganic phosphate)

in general, __ is an enzyme that utilizes ATP, whereas __ does not use ATP

synthetase, synthase

how many high energy phosphate bonds (ATP) are lost in the reaction of fatty acid -> CoA ester?

2

is the CoA fatty acid ester able to pass through the inner mitochondrial membrane?

no

fatty acids esterified with __ are capable of being transported across the inner mitochondrial membrane

carnitine

the enzyme __ __ converts the fatty acid CoA ester to the O-acylated carnitine which is transported across the mitochondrial membrane by the transporter

carnitine acyltransferase I (CA1)

once on the matrix side of the inner mitochondrial membrane, the acylated carnitine is transformed by carnitine acyltransferase II (CA2) back into the __ __ ___

fatty acyl CoA

O-acylcarnitine is transported across the inner mitochondrial membrane by __/__ shuttle

acylcarnitine/carnitine

enzyme __ occurs only in outer membrane of mitochondria

CA1

__ reforms the CoA ester and releases carnitine

CA2

once inside the mitochondrial matrix, the fatty acyl CoA ester undergoes 4 reactions, the first reaction is catalyzed by __ __ __ and __ is converted to __ in the process

acyl CoA dehydrogenase, FAD, FADH2

the double bond that is formed in the first dehydrogenation reaction of fatty acyl CoA ester in the mitochondrial matrix has a __ stereochemistry

trans

in the second reaction of fatty acyl CoA in the mitochondrial matrix, __ is added across the double bond and the enzyme used is __ __ __

water, enoyl CoA hydratase

the third reaction in the sequence of 4 reactions that occurs in the mitochondrial matrix is another __ reaction, but in this case, the alcohol is oxidized to a ketone using __ as the oxidizing agent

dehydrogenation, NAD+

the b-ketoacyl CoA formed in the third step in the mitochondrial matrix is catalayzed by __ which cleaves off a molecule of acetyl CoA, leaving the __ __ of the original fatty acid but with __ less carbon atoms

thiolase, CoA ester, 2

__ and __ are generated in beta oxidation

FADH2, NADH

the 4 reaction sequence is repeated, losing 2 carbon atoms each cycle, in the final reaction sequence in which the 4-carbon butyroyl CoA thioester is oxidized, the final thiolase reaction produces two molecules of __ __

acetyl CoA

example of beta oxidation: palmitoyl CoA (16 carbon atoms) goes through _ cycles of beta oxidation and is completely broken down to __ molecules of acetyl CoA, generating _ FADH2 and _ NADH

7, 8, 7, 7

how many molecules of ATP are generated from FADH2 when palmitoyl CoA (16 carbons) undergoes the beta oxidation process?

10.5 (takes 7 cycles, forms 7 FADH2, 1 FADH2 = 1.5 ATP, 7X1.5 = 10.5)

how many molecules of ATP are generated from NADH when palmitoyl CoA (16 carbons) undergoes the beta oxidation process?

17.5 (takes 7 cycles, forms 7 NADH, 1 NADH = 2.5 ATP, 7x2.5 = 17.5)

how many molecules of ATP are formed for every molecule of palmitoyl CoA that is completely oxidized (beta oxidation plus citric acid cycle) to carbon dioxide and water?

106 (not 108, have to subtract 2 ATP b/c we have to use them in esterification to get the faty acid into the system)

under intracellular conditions, free energy recovery is remarkably ___

efficient

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