BCH 202 Fatty Acids

Question 1

Definition of fatty acids

Answer 1

A fatty acid contains a long hydrocarbon chain and a terminal carboxylate group. The hydrocarbon chain may be saturated (with no double bond) or may be unsaturated (containing double bond).

Question 2

Fatty acids can be obtained from-

Answer 2

Diet
Adipolysis
De novo synthesis

Question 3

What is de novo synthesis

Answer 3

the synthesis of complex molecules from simple molecules such as sugars or amino acids

Question 4

Functions of a fatty acids

Answer 4

1)Fatty acids are building blocks of
phospholipids and glycolipids.

2)Many proteins are modified by the covalent attachment of fatty acids, which target them to membrane locations

3)Fatty acids are fuel molecules. They are stored as triacylglycerols. Fatty acids mobilized from triacylglycerols are oxidized to meet the energy needs of a cell or organism.

4)Fatty acid derivatives serve as hormones and intracellular messengers e.g. steroids, sex hormones and prostaglandins.

Question 5

How are fatty acids oxidized?

Answer 5

1.Beta oxidation- Major mechanism, occurs in the mitochondria matrix. 2-C units are released as acetyl CoA per cycle.

2)Alpha oxidation- Predominantly takes place in brain and liver, one carbon is lost in the form of CO2 per cycle.

3)Omega oxidation- Minor mechanism, but becomes important in conditions of impaired beta oxidation

4)Peroxisomal oxidation- Mainly for the trimming of very long chain fatty acids.

Question 6

What are triacylglycerol/ Triglycerides

Answer 6

Triacylglycerols (triglycerides) are the most abundant dietary lipids.
Each triacylglycerol has a glycerol backbone to which are esterified 3 fatty acids

Question 7

Most triacylglycerols are “mixed,” meaning?

Answer 7

The 3 fatty acids differ in chain length & number of double bonds.

Question 8

Describe the action of lipase on triacylglycerol

Answer 8

Lipases hydrolyze triacylglycerols, yielding glycerol and three fatty acids.
The glycerol cannot be metabolized by the adipocytes because they lack glycerol kinase.
The glycerol is transported to the liver where it will be phosphorylated to give glycerol phosphate

Free fatty acids are transported in the blood bound to albumin, a plasma protein produced by the liver.

Question 9

Stages of fatty acid oxidation

Answer 9

(1) Activation of fatty acids takes place on the outer mitochondrial membrane
(2) Transport into the mitochondria
(3) Degradation to two-carbon fragments (as acetyl CoA) in the mitochondrial matrix (β-oxidation pathway)

Question 10

Describe Fatty acid activation

Answer 10

Acyl-CoA Synthases (Thiokinases) of ER & outer mitochondrial membranes catalyze activation of long chain fatty acids, esterifying them to coenzyme A.
This process is ATP-dependent and occurs in 2 steps.
There are different Acyl-CoA Synthases for fatty acids of different chain lengths.

Question 11

Write a summary of fatty aid activation

Answer 11

fatty acid + ATP + HS-CoA (coenzyme A) ====>acyl-CoA + AMP + 2 Pi

Question 12

Where does fatty acid b-oxidation considered to occur?

Answer 12

In the mitochondrial matrix

Question 13

In order for fatty acids to be oxidized they must

Answer 13

enter the mitochondrial matrix

Question 14

Fatty acyl-CoA formed outside cannot pass through the outer mitochondrial membrane, but can penetrate the inner membrane. T/F

Answer 14

FALSE

Fatty acyl-CoA formed outside can pass through the outer mitochondrial membrane, but cannot penetrate the inner membrane.

Question 15

What is Carnitine Palmitoyl Transferases?

Answer 15

Carnitine Palmitoyl Transferases catalyze transfer of a fatty acid between the thiol of Coenzyme A and the hydroxyl on carnitine.

Question 16

Where can beta oxidation of FA’s take place

Answer 16

Outer mitochondrial membrane
Peroxisomes
ER

Question 17

Describe the transport of FA’s from the outer mitochondrial membrane and inner mitochondrial membrane

Answer 17

Carnitine-mediated transfer of the fatty acyl into the mitochondrial matrix is a 3-step process:
1. Carnitine Palmitoyl Transferase I, an enzyme on the cytosolic surface of the outer mitochondrial membrane, transfers a fatty acid from CoA to the OH on carnitine.
2. An antiporter in the inner mitochondrial membrane mediates the exchange of carnitine for acylcarnitine.
3. Carnitine Palmitoyl Transferase II, an enzyme within the matrix, transfers the fatty acid from carnitine to CoA. (Carnitine exits the matrix in step 2.)
The fatty acid is now esterified to CoA in the matrix.

Question 18

Describe the control of fatty acid oxidation

Answer 18

Malonyl-CoA (which is also a precursor for fatty acid synthesis) inhibits Carnitine Palmitoyl Transferase I.
Malonyl-CoA thus inhibits fatty acid oxidation by preventing its transport into mitochondria.

Question 19

When does FA control begin?

Answer 19

Control of fatty acid oxidation is exerted mainly at the step of fatty acid entry into mitochondria.

Question 20

List the 4 reactions involved in the degradation of saturated acyl Co A (beta pathway)

Answer 20

1) Oxidation by flavin adenine dinucleotide (FAD)
2) Hydration
3) Oxidation by NAD+
4) Thiolysis by Co ASH

Question 21

Describe Step 1 of the b-Oxidation Pathway

Answer 21

Step 1
Acyl-CoA Dehydrogenase catalyzes the oxidation of the fatty acid of acyl-CoA to produce a double bond between carbon atoms 2 & 3.

There are different Acyl-CoA Dehydrogenases for short (4-6 C), medium (6-10 C),long and very long (12-18 C) chain fatty acids.

Question 22

Function of FAD in step 1

Answer 22

FAD is the prosthetic group that functions as e- acceptor for Acyl-CoA Dehydrogenase.

Question 23

Describe Step 2 of the b-Oxidation Pathway

Answer 23

Step 2.
Enoyl-CoA Hydratase is the hydration of the double bond produced in the 1st step, yielding L-hydroxy acyl-Coenzyme A.

Question 24

Describe Step 3 of the b-Oxidation Pathway

Answer 24

Step 3.
Hydroxyacyl-CoA Dehydrogenase catalyzes oxidation of the hydroxyl in the b position (C3) to a ketone.
NAD+ is the electron acceptor.

Question 25

Describe Step 4 of the b-Oxidation Pathway

Answer 25

b-Ketothiolase catalyzes thiolytic cleavage.
Thiol sulfur of CoA attacks the b-keto carbon
Acetyl-CoA is released, leaving the fatty acyl in thioester linkage to the CoA -fatty acyl-CoA (2 C less).

Question 26

Summary of one round of the b-oxidation pathway:

Answer 26

fatty acyl-CoA + FAD + NAD+ + HS-CoA 
fatty acyl-CoA (2 C less) + FADH2 + NADH + H+
+ acetyl-CoA
The b-oxidation pathway is cyclic.
The product, 2 carbons shorter, is the input to another round of the pathway.
If, as is usually the case, the fatty acid contains an even number of C atoms, in the final reaction cycle butyryl-CoA is converted to 2 molecules of acetyl-CoA.

Question 27

What does one round of the cycle produce?

Answer 27

One round of β oxidation: 4 enzyme steps produce acetyl CoA from fatty acyl CoA
Each round generates one molecule each of:
FADH2NADHAcetyl CoA Fatty acyl CoA (2 carbons shorter each round)

Question 28

Fate of FADH2 & NADH (products of beta oxidation)

Answer 28

FADH2 & NADH produced during fatty acid oxidation enter into the electron transport chain (ETC) to generate ATP.

Question 29

Fate of Acetyl CoA (product of beta oxidation)

Answer 29

Acetyl-CoA can enter Krebs cycle, yielding additional NADH, FADH2, and ATP.

Question 30

Which reaction is a major source of cell ATP? Why?

Answer 30

Fatty acid oxidation is a major source of cell ATP
The reactions presented accomplish catabolism of a fatty acid with an even number of C atoms & no double bonds.

Question 31

Characteristics of the α- OXIDATION OF FATTY ACIDS

Answer 31

Takes place in the microsomes of brain and liver,
It involves decarboxylation process for the removal of single carbon atom at one time with the resultant production of an odd chain fatty acid that can be subsequently oxidized by beta oxidation for energy production.
It is strictly an aerobic process
No prior activation of the fatty acid is required.
The process involves hydroxylation of the alpha carbon with a specific α-hydroxylase

Question 32

Characteristics of the ω-OXIDATION OF FATTY ACIDS

Answer 32

ω-OXIDATION OF FATTY ACIDS
Fatty acids may be, oxidized at the ω-carbon of the chain by enzymes in the endoplasmic reticulum. ω-carbon is a carbon farthest from the carboxyl end
The ω-methyl group is first oxidized to an alcohol (CH2OH) by hydroxylase that uses cytochrome P450, molecular oxygen and NADPH in the endoplasmic reticulum
The alcoholic group is subsequently oxidized to –COOH by dehydrogenase and thus forming a dicarboxylic acid
Short chain dicarboxylic acid such as pimelic acid, a precursor of biotin is formed by ω-oxidation

Question 33

Describe the formation of ketone bodies during fasting

Answer 33

During fasting or carbohydrate starvation, oxaloacetate is depleted in liver due to gluconeogenesis.
This impedes entry of acetyl-CoA into Krebs cycle.
Acetyl-CoA in liver mitochondria is converted then to ketone bodies, acetoacetate & b-hydroxybutyrate

Question 34

Briefly describe the REGULATION OF FATTY ACID OXIDATION

Answer 34

In well-fed state due to increased level of insulin, concentration of malonyl-CoA increases which inhibits CAT-I and leads to decrease in fatty acid oxidation
In starvation, due to increased level of glucagon, concentration of malonyl-CoA decreases thereby stimulating fatty-acid oxidation