Module 8 - Fatty Acid Degredation Flashcards

1
Q

β-oxidation

A

the process whereby fatty acids are degraded to acetyl CoA, NADH and FADH2

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2
Q

Carnitine

A

a biomolecule to which fatty acids are attached which facilitates their transport into the mitochondrial matrix for oxidation.

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3
Q

Hormone-Sensitive Lipase

A

an enzyme in adipose that is activated by hormone-stimulated cAMP signalling system, through covalent phosphorylation of the enzyme.

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4
Q

Ketone Bodies

A

water-soluble biomolecules that are formed in the liver from acetyl CoA and which can be used by various tissues as an energy source.

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5
Q

Fatty acids are degraded by a process called β-oxidation.

A

This is a repetitive process whereby long-chain fatty acids are sequentially degraded to acetyl CoA, depending on the length of the fatty acid.

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6
Q

What is the structure of a fatty acid?

A

a long hydrocarbon chain with a carboxylic acid group on the end, thus the name “fatty acid”

The length of fatty acids varies, with commonly occurring ones ranging from 12-20 carbons in length

The hydrocarbon chains, which are very non-polar in nature, can be fully reduced (consisting of (-CH2)n) or can have some double bonds

Most double bonds in fatty acids are in the cis-configuration, which means that the substituents on each side of the double bond are on the same side.

This induces a kink in the hydrocarbon chain, which affects their physical properties such as lowering the melting point of the fatty acid.

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7
Q

How are fatty acids stored?

A

as triacylglycerol, a neutral lipid, in adipose tissue

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8
Q

What is visceral adipose tissue?

A

fat that accumulates in the abdomen around heart, liver and intestine in obese individuals

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9
Q

Why is adipose tissue necessary?

A

it stores an important fuel

it secretes small biomolecules called “adipokines” which control overall body metabolism and appetite.

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10
Q

How are fatty acids used in the body as fuel?

A

they have to be cleaved off of triacylglycerol (or mobilized) by an enzyme called lipase, and then released into the blood

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11
Q

What is the first stage of fatty acid degradation?

A

Mobilization of Fatty Acids from Triacylglycerol in Adipose Tissue

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12
Q

How is Triacylglycerol (also called triglyceride) in adipose broken down by the action of several lipases into glycerol and three fatty acids?

A

a hydrolysis reaction, and three water molecules are used to cleave off the three fatty acid residues

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13
Q

There are 3 different lipases involved in breaking down triglycerol.

A

The enzymes that cleave off the first two fatty acids, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HS-lipase), are regulated by hormones that signal a need for more fuel.

MAG Lipase is the third lipase that acts on monoacylglycerol to release the third fatty acid.

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14
Q

ATGL and HS-lipase are regulated by which hormones?

A

epinephrine and glucagon

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15
Q

How do epinephrine and glucagon activate the enzymes?

A

bind to their respective receptor on the surface of adipose cells, and activate the cAMP signalling system

cAMP activates protein kinase A, which activates ATGL and HS-lipase

This control system ensures that triacylglycerol is degraded only when the body is low on energy supply.

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16
Q

What happens when the fatty acid degradation from the first step is complete?

A

the fatty acids and glycerol are both released into the blood.

Fatty acids are water-insoluble, and are transported in the blood bound to the blood protein albumin.

fatty acids go to many tissues in the body where they are used as fuel

glycerol is taken up by the liver, where it is converted to dihydroxyacetone phosphate

17
Q

Diagram of the fate of glycerol and fatty acids after the first step.

A
18
Q

What is the second stage of fatty acid degradation?

A

Activation of Fatty Acids and Transport to the Mitochondria

19
Q

When fatty acids arrive at the cell, they diffuse across the cell membrane with help from special proteins.

A

Fatty acids are activated by reacting with Coenzyme A, which occurs on the outer mitochondrial membrane.

The reaction consumes one ATP which is broken down into AMP and PPi, the latter which is quickly degraded to two Pi.

Thus, two high-energy bonds are broken down for every CoA attached to a fatty acid

20
Q

activated fatty acids are still not able to be transported across the inner mitochondrial membrane.

A

At the surface of the inner mitochondrial membrane, on the cytoplasmic side, the acyl group of Acyl CoA gets transferred to a biomolecule called carnitine, forming acyl carnitine.

The enzyme catalyzing this reaction is called Carnitine acyltransferase I.

21
Q

Acyl carnitine is able to be transported across the inner mitochondrial by a specific translocase

A

Once inside the mitochondria, the reverse reaction from that shown above is catalyzed by Carnitine acyltransferase II, which reconstitutes acyl CoA and releases free carnitine.

Carnitine is shuttled back into the cytosol so it can be re-esterified to another fatty acid to assist in bringing it into the mitochondria.

22
Q

What is the third stage of fatty acid degradation?

A

Degradation of Fatty Acyl CoA to Acetyl CoA

23
Q

During the third stage, The fatty acyl CoA is now in the mitochondrial matrix where it can undergo β-oxidation. How many reactions are involved with β-oxidation?

A

4

24
Q

What is the first step of β-oxidation?

A

Enzyme - Acyl CoA dehydrogenase

the bond between the α and β carbons (in red) becomes oxidized to a double bond, and the electrons are used to reduce FAD to FADH2.

FADH2 can then donate its electrons to the electron transport chain to produce ATP

25
Q

What is the second step of β-oxidation?

A

In this hydration reaction, water is added across the double bond, which puts an –OH on the β-carbon, and a hydrogen on the α-carbon.

The product is 3-hydroxyacyl CoA since the hydroxyl is on the number 3, or β, carbon.

26
Q

What is the third step of β-oxidation?

A

Enzyme – β-hydroxyacyl CoA dehydrogenase

In this oxidation reaction, 3-hydroxyacyl CoA is oxidized to form 3-ketoacyl CoA and NAD+ becomes reduced.

Note that the β-carbon now is fully oxidized, having started out as a CH2 and is now a C=O.

The NADH produced can donate its electrons to the electron transport chain.

27
Q

What is the fourth step of β-oxidation?

A

Enzyme – Thiolase or 3-ketoacyl thiolase

a two-carbon unit is cleaved off the end of the 3-ketoacyl CoA, which is an acetyl CoA unit.

This cleavage is achieved using free CoA, with the –SH group attacking the bond between the α and β-carbon.

This gives the second product, acyl CoA, which is two carbons shorter than what was started with.

This now goes through the four reactions above again, releasing yet another acetyl CoA. When the acyl CoA is degraded to a four-carbon unit, the final round of β-oxidation releases two acetyl CoA and completes the β-oxidation.

28
Q

Let’s consider the oxidation of palmitate, a common 16-carbon fatty acid with no double bonds. How much ATP is generated?

A

108 ATP generated but when you remove the 2 ATP that was required to activate the fatty acid the total becomes 106

29
Q

How can 1 molecule of palmitate generate so much ATP?

A

Palmitate requires 7 rounds of β-oxidation in order to fully degrade it to acetyl CoA units.

Each cycle produces 1 FADH2 and 1 NADH which equals 7FADH2 and 7NADH in total.

Each NADH generates 2.5 ATP via oxidative phosphorylation for a total of 17.5

Each FADH2 generates 1.5 ATP for a total of 10.5

7 rounds of β-oxidation generates 8 acetylCoA and each acetylCoA produces 10 ATP in the Citric Acid Cycle so that is 80 ATP in total.

30
Q

Ketone Bodies Are Another Fuel Source Derived from Fatty Acids

A

Most of the acetyl CoA produced from β-oxidation enter the citric acid cycle, however in liver a small portion of the acetyl CoA is used to synthesize ketone bodies.

31
Q

What are ketone bodies?

A

an important and useful fuel molecule since they are water soluble, and they can be used as fuel by the brain while fatty acids cannot due to their inability to cross the blood brain barrier.

Other tissues such as heart and kidney may even use ketone bodies preferentially over glucose.

32
Q

The degradation of ketone bodies

A