L25- Fatty Acid Biosynthesis

Question 1

In which cellular compartment does fatty acid synthesis occur?

Answer 1

Cytoplasm.

Question 2

What molecule is the major source of carbons for fatty acid chain synthesis?

Answer 2

Acetyl-CoA (from mitochondria).

Question 3

In order to direct acetyl-CoA into fatty acid synthesis, the TCA cycle must be inhibited. Under high energy conditions, which TCA cycle enzyme is inhibited to favor fatty acid synthesis?

Answer 3

Isocitrate dehydrogenase.

Question 4

The last two carbons of a fatty acid chain come from which molecule? The remaining carbons come from which molecule?

Answer 4

The last two carbons (the carbons at the omega end) come from acetyl-CoA. The remaining carbons come from malonyl-CoA.

Question 5

What molecule crosses the mitochondrial membrane into the cytoplasm as a means to generate a cytoplasmic pool of acetyl-CoA?

Answer 5

Citrate.

Question 6

What is the reaction catalyzed by the enzyme citrate lyase?

Answer 6

It converts citrate (using ATP and CoASH) into acetyl-CoA and oxaloacetate (and ADP + Pi).

Question 7

What enzyme converts acetyl-CoA to malonyl-CoA in the cytoplasm?

Answer 7

Acetyl CoA carboxylase.

Question 8

What is the cofactor for acetyl CoA carboxylase?

Answer 8

Biotin (it is a cofactor for every carboxylase).

Question 9

At which step is fatty acid synthesis regulated?

Answer 9

At acetyl CoA carboxylase (conversion of acetyl-CoA to malonyl-CoA in the cytoplasm).

Question 10

What is the mechanism by which acetyl CoA carboxylase is deactivated?

Answer 10

In the presence of excess fatty acyl CoA and malonyl-CoA, glucagon and epinephrine stimulate phosphorylation of the enzyme, which in turn leads to depolymerization (i.e. deactivation) of its subunits. The enzyme also undergoes depolymerization when citrate levels are lowered.

Question 11

On which large polymeric protein does fatty acid synthesis occur?

Answer 11

Fatty acid synthase.

Question 12

What two residues on fatty acid synthase play a major role in fatty acid synthesis?

Answer 12

An -SH residue on a cysteine and a phosphopantetheine group capable or forming a thioester bond with fatty acids on which fatty acid chains grow in length.

Question 13

True or False. The chemistry of the steps involved in fatty acid synthesis are the reverse of those involved in fatty acid oxidation.

Answer 13

True.

Question 14

In mammals, fatty acid synthesis on fatty acid synthase stops when the fatty acid chain reaches how many carbons in length?

Answer 14

16 carbons (the name of this patty acid is palmitate).

Question 15

What is the enzyme that cleaves palmitoyl-CoA from fatty acid synthase?

Answer 15

Thioesterase.

Question 16

Which group on fatty acid synthase serves as the acceptor of acetyl-CoA and malonyl-CoA?

Answer 16

The phosphopantetheine group (Pan).

Question 17

What kind of bond is formed between the malonyl group of malonyl-CoA and the phosphopantetheine group (Pan) of fatty acid synthase?

Answer 17

A thioester bond.

Question 18

What happens during the condensation step of fatty acid synthesis?

Answer 18

The acetyl group on cysteine is condensed with the malonyl group on phosphopantetheine (Pan), forming the four carbon acetoacetyl-CoA while also liberating a carbon dioxide from the malonyl group.

Question 19

True or False. The carbon dioxide that is liberated during the condensation reaction of fatty acid synthesis is the same as the carbon dioxide that was added to acetyl-CoA by acetyl CoA carboxylase.

Answer 19

True.

Question 20

Where on fatty acid synthase do the condensation, reduction and dehydration occur?

Answer 20

On the phosphopantetheine group (Pan).

Question 21

What is the cofactor required for the reduction reactions that occur on fatty acid synthase in fatty acid synthesis?

Answer 21

NADPH.

Question 22

What are two sources of the NADPH required for the reduction reactions of fatty acid synthesis?

Answer 22

The pentose phosphate pathway and the reaction catalyzed by NADP+-linked malate dehydrogenase (which converts malate to pyruvate).

Question 23

How many molecules of acetyl-CoA, ATP and NADPH are required to form one molecule of palmitate?

Answer 23

8 acetyl-CoA’s, 15 ATP’s and 14 NADPH’s.

Question 24

True or False. Conversion of carbohydrates to fatty acids is 100% efficient.

Answer 24

False. Its efficiency is approximately 81%.

Question 25

True or False. The conversion of carbohydrates to fatty acids is a reversible process.

Answer 25

False. There are no mammalian enzymes that can readily convert acetyl-CoA to pyruvate.

Question 26

Elongation of fatty acids in the mitochondria involve the addition of what molecule to a fatty acyl-CoA?

Answer 26

Acetyl-CoA.

Question 27

Elongation of fatty acids in the endoplasmic reticulum involves the addition of what molecule to a fatty acyl-CoA?

Answer 27

Malonyl-CoA. Note that since fatty acids are elongated two carbons at a time, elongation in the ER also generates a carbon dioxide since malonyl-CoA is a three carbon molecule.

Question 28

Mammalian tissues can desaturate fatty acids by adding double bonds to a fatty acid chain unless the double bond is closer than which omega number (i.e. no closer than how many carbons from the methyl end)?

Answer 28

Omega-7.

Question 29

What are essential fatty acids?

Answer 29

Fatty acids we cannot produce: fatty acids that have double bonds close to carbon 7 from the methyl group (fatty acids with an omega number less than 7).

Question 30

True or False. Elongation of fatty acids results in an increase in the fatty acid’s omega number.

Answer 30

False. Elongation does not change the omega number because it occurs at the carboxyl end, not the methyl end of the fatty acid.

Question 31

What essential fatty acid is the precursor for arachidonic acid?

Answer 31

Linoleic acid.

Question 32

What essential fatty acid is the precursor for eicosapentaenoic acid?

Answer 32

Alpha-linolenic acid.

Question 33

In which cellular compartment does elongation of fatty acids occur?

Answer 33

The ER.

Question 34

Hydroxylation of 2-carbon fatty acids is important for which tissue?

Answer 34

Nervous tissue.

Question 35

What are the precursors for synthesis of triacylglycerols in the liver and adipose tissue?

Answer 35

Glycerol-3-phosphate and fatty acyl CoA.

Question 36

What are the precursors for synthesis of triacylglycerols in the intestines?

Answer 36

2-monoacylglycerol (2-MAG).

Question 37

Name two enzymes that can generate glycerol-3-phosphate directly from glycerol.

Answer 37

Glycerol phosphate dehydrogenase (from glycolysis) and glycerol kinase.

Question 38

Why is adipose tissue unable to generate glycerol-3-phosphate directly from glycerol?

Answer 38

It does not have the enzyme glycerol kinase.

Question 39

What is the product of the acylation of glycerol-3-phosphate with two molecules of fatty acyl CoA’s?

Answer 39

Phosphatidic acid.

Question 40

Dephosphorylation followed by acylation of phosphatidic acid produces what molecule?

Answer 40

Diacylglycerol, which can then be acylated to form triacylglycerol.